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. 2024 Jan 16;1(1):CD013295.
doi: 10.1002/14651858.CD013295.pub2.

Pharmacological interventions for the prevention of bleeding in people undergoing elective hip or knee surgery: a systematic review and network meta-analysis

Victoria N Gibbs  1 , Rita Champaneria  1   2 , Josie Sandercock  1   2 , Nicky J Welton  3 , Louise J Geneen  1   2 , Susan J Brunskill  1   2 , Carolyn Dorée  1   2 , Catherine Kimber  1   2 , Antony Jr Palmer  4 , Lise J Estcourt  5
Affiliations

Pharmacological interventions for the prevention of bleeding in people undergoing elective hip or knee surgery: a systematic review and network meta-analysis

Victoria N Gibbs et al. Cochrane Database Syst Rev. .

Abstract

Background: Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care.

Objectives: To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology.

Search methods: We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP).

Selection criteria: We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants.

Data collection and analysis: We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received.

Main results: We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials).

Authors' conclusions: We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.

PubMed Disclaimer

Conflict of interest statement

Victoria N Gibbs: funded by an NIHR Cochrane Programme Grant

Rita Champaneria: funded by an NIHR Cochrane Programme Grant

Antony JR Palmer: none known

Carolyn Dorée: none known

Susan J Brunskill is an editor of Cochrane Haematology (Methodologists and Clinicians); she has not been involved in the editorial process for the article.

Lise J Estcourt is a Co‐ordinating Editor of Cochrane Haematology; she has not been involved in the editorial process for the article.

Josie Sandercock: none known

Louise J Geneen: none known

Catherine Kimber: none known

Figures

1
1
Network plot allogeneic blood transfusion
2
2
Network plot deep vein thrombosis
3
3
PRISMA diagram
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
5
5
6
6
7
7
8
8
9
9
1.1
1.1. Analysis
Comparison 1: Results included in the network meta‐analyses, Outcome 1: Need for allogeneic blood transfusion (only trials included in the NMA)
1.2
1.2. Analysis
Comparison 1: Results included in the network meta‐analyses, Outcome 2: Units of red blood cells transfused (only trials included in the NMA)
1.3
1.3. Analysis
Comparison 1: Results included in the network meta‐analyses, Outcome 3: Risk of experiencing DVT (only trials included in the NMA)
1.4
1.4. Analysis
Comparison 1: Results included in the network meta‐analyses, Outcome 4: Length of hospital stay (only trials included in the NMA)
2.1
2.1. Analysis
Comparison 2: TXA IV vs placebo, Outcome 1: Need for allogeneic blood transfusion
2.2
2.2. Analysis
Comparison 2: TXA IV vs placebo, Outcome 2: All‐cause mortality
2.3
2.3. Analysis
Comparison 2: TXA IV vs placebo, Outcome 3: Units of red blood cells transfused
2.4
2.4. Analysis
Comparison 2: TXA IV vs placebo, Outcome 4: Reoperation
2.5
2.5. Analysis
Comparison 2: TXA IV vs placebo, Outcome 5: Length of hospital stay
2.6
2.6. Analysis
Comparison 2: TXA IV vs placebo, Outcome 6: Risk of experiencing DVT
2.7
2.7. Analysis
Comparison 2: TXA IV vs placebo, Outcome 7: Risk of experiencing PE
2.8
2.8. Analysis
Comparison 2: TXA IV vs placebo, Outcome 8: Risk of experiencing MI
2.9
2.9. Analysis
Comparison 2: TXA IV vs placebo, Outcome 9: Risk of experiencing CVA
2.10
2.10. Analysis
Comparison 2: TXA IV vs placebo, Outcome 10: Risk of having suspected serious drug reactions
3.1
3.1. Analysis
Comparison 3: TXA oral vs placebo, Outcome 1: Need for allogeneic blood transfusion
3.2
3.2. Analysis
Comparison 3: TXA oral vs placebo, Outcome 2: All‐cause mortality
3.3
3.3. Analysis
Comparison 3: TXA oral vs placebo, Outcome 3: Length of hospital stay
3.4
3.4. Analysis
Comparison 3: TXA oral vs placebo, Outcome 4: Risk of experiencing DVT
3.5
3.5. Analysis
Comparison 3: TXA oral vs placebo, Outcome 5: Risk of experiencing PE
3.6
3.6. Analysis
Comparison 3: TXA oral vs placebo, Outcome 6: Risk of experiencing MI
3.7
3.7. Analysis
Comparison 3: TXA oral vs placebo, Outcome 7: Risk of experiencing CVA
4.1
4.1. Analysis
Comparison 4: TXA topical vs placebo, Outcome 1: Risk of allogeneic blood transfusion
4.2
4.2. Analysis
Comparison 4: TXA topical vs placebo, Outcome 2: All‐cause mortality
4.3
4.3. Analysis
Comparison 4: TXA topical vs placebo, Outcome 3: Reoperation
4.4
4.4. Analysis
Comparison 4: TXA topical vs placebo, Outcome 4: Length of hospital stay
4.5
4.5. Analysis
Comparison 4: TXA topical vs placebo, Outcome 5: Risk of experiencing DVT
4.6
4.6. Analysis
Comparison 4: TXA topical vs placebo, Outcome 6: Risk of experiencing PE
4.7
4.7. Analysis
Comparison 4: TXA topical vs placebo, Outcome 7: Risk of experiencing CVA
4.8
4.8. Analysis
Comparison 4: TXA topical vs placebo, Outcome 8: Risk of transfusion reactions
5.1
5.1. Analysis
Comparison 5: TXA IV + TXA topical vs placebo, Outcome 1: Risk of allogeneic blood transfusion
5.2
5.2. Analysis
Comparison 5: TXA IV + TXA topical vs placebo, Outcome 2: Length of hospital stay
5.3
5.3. Analysis
Comparison 5: TXA IV + TXA topical vs placebo, Outcome 3: Risk of experiencing DVT
5.4
5.4. Analysis
Comparison 5: TXA IV + TXA topical vs placebo, Outcome 4: Risk of experiencing PE
6.1
6.1. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 1: Risk of allogeneic blood transfusion
6.2
6.2. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 2: All‐cause mortality
6.3
6.3. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 3: Units of red blood cells transfused
6.4
6.4. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 4: Reoperation
6.5
6.5. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 5: Length of hospital stay
6.6
6.6. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 6: Risk of experiencing DVT
6.7
6.7. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 7: Risk of experiencing PE
6.8
6.8. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 8: Risk of experiencing MI
6.9
6.9. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 9: Risk of experiencing CVA
6.10
6.10. Analysis
Comparison 6: TXA IV lower dose vs TXA IV higher dose, Outcome 10: Risk of suspected serious drug reactions
7.1
7.1. Analysis
Comparison 7: TXA IV vs TXA oral, Outcome 1: Risk of allogeneic blood transfusion
7.2
7.2. Analysis
Comparison 7: TXA IV vs TXA oral, Outcome 2: Units of red blood cells transfused
7.3
7.3. Analysis
Comparison 7: TXA IV vs TXA oral, Outcome 3: Length of hospital stay
7.4
7.4. Analysis
Comparison 7: TXA IV vs TXA oral, Outcome 4: Risk of experiencing DVT
7.5
7.5. Analysis
Comparison 7: TXA IV vs TXA oral, Outcome 5: Risk of experiencing PE
7.6
7.6. Analysis
Comparison 7: TXA IV vs TXA oral, Outcome 6: Risk of experiencing CVA
8.1
8.1. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 1: Risk of allogeneic blood transfusion
8.2
8.2. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 2: All‐cause mortality
8.3
8.3. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 3: Reoperation
8.4
8.4. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 4: Length of hospital stay
8.5
8.5. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 5: Risk of experiencing DVT
8.6
8.6. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 6: Risk of experiencing PE
8.7
8.7. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 7: Risk of experiencing MI
8.8
8.8. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 8: Risk of experiencing CVA
8.9
8.9. Analysis
Comparison 8: TXA IV vs TXA topical, Outcome 9: Risk of suspected serious drug reactions
9.1
9.1. Analysis
Comparison 9: TXA oral lower dose vs TXA oral higher dose, Outcome 1: Risk of allogeneic blood transfusion
9.2
9.2. Analysis
Comparison 9: TXA oral lower dose vs TXA oral higher dose, Outcome 2: All‐cause mortality
9.3
9.3. Analysis
Comparison 9: TXA oral lower dose vs TXA oral higher dose, Outcome 3: Risk of experiencing DVT
9.4
9.4. Analysis
Comparison 9: TXA oral lower dose vs TXA oral higher dose, Outcome 4: Risk of experiencing PE
9.5
9.5. Analysis
Comparison 9: TXA oral lower dose vs TXA oral higher dose, Outcome 5: Risk of experiencing MI
9.6
9.6. Analysis
Comparison 9: TXA oral lower dose vs TXA oral higher dose, Outcome 6: Risk of experiencing CVA
10.1
10.1. Analysis
Comparison 10: TXA topical lower dose vs TXA topical higher dose, Outcome 1: Risk of allogeneic blood transfusion
10.2
10.2. Analysis
Comparison 10: TXA topical lower dose vs TXA topical higher dose, Outcome 2: All‐cause mortality
10.3
10.3. Analysis
Comparison 10: TXA topical lower dose vs TXA topical higher dose, Outcome 3: Reoperation
10.4
10.4. Analysis
Comparison 10: TXA topical lower dose vs TXA topical higher dose, Outcome 4: Risk of experiencing CVA
10.5
10.5. Analysis
Comparison 10: TXA topical lower dose vs TXA topical higher dose, Outcome 5: Risk of suspected serious drug reactions
11.1
11.1. Analysis
Comparison 11: TXA IV vs aprotinin, Outcome 1: Risk of allogeneic blood transfusion
11.2
11.2. Analysis
Comparison 11: TXA IV vs aprotinin, Outcome 2: Risk of experiencing DVT
12.1
12.1. Analysis
Comparison 12: TXA IV vs EACA, Outcome 1: Risk of allogeneic blood transfusion
12.2
12.2. Analysis
Comparison 12: TXA IV vs EACA, Outcome 2: Units of red blood cells transfused
12.3
12.3. Analysis
Comparison 12: TXA IV vs EACA, Outcome 3: Reoperation
12.4
12.4. Analysis
Comparison 12: TXA IV vs EACA, Outcome 4: Length of hospital stay
12.5
12.5. Analysis
Comparison 12: TXA IV vs EACA, Outcome 5: Risk of experiencing DVT
12.6
12.6. Analysis
Comparison 12: TXA IV vs EACA, Outcome 6: Risk of experiencing PE
12.7
12.7. Analysis
Comparison 12: TXA IV vs EACA, Outcome 7: Risk of experiencing MI
12.8
12.8. Analysis
Comparison 12: TXA IV vs EACA, Outcome 8: Risk of experiencing CVA
13.1
13.1. Analysis
Comparison 13: TXA oral vs EACA oral, Outcome 1: Risk of allogeneic blood transfusion
13.2
13.2. Analysis
Comparison 13: TXA oral vs EACA oral, Outcome 2: All‐cause mortality
13.3
13.3. Analysis
Comparison 13: TXA oral vs EACA oral, Outcome 3: Reoperation
13.4
13.4. Analysis
Comparison 13: TXA oral vs EACA oral, Outcome 4: Risk of experiencing DVT
13.5
13.5. Analysis
Comparison 13: TXA oral vs EACA oral, Outcome 5: Risk of experiencing PE
13.6
13.6. Analysis
Comparison 13: TXA oral vs EACA oral, Outcome 6: Risk of experiencing MI
13.7
13.7. Analysis
Comparison 13: TXA oral vs EACA oral, Outcome 7: Risk of experiencing CVA
13.8
13.8. Analysis
Comparison 13: TXA oral vs EACA oral, Outcome 8: Risk of suspected serious drug reactions
14.1
14.1. Analysis
Comparison 14: TXA IV vs desmopressin, Outcome 1: Risk of allogeneic blood transfusion
14.2
14.2. Analysis
Comparison 14: TXA IV vs desmopressin, Outcome 2: Length of hospital stay
14.3
14.3. Analysis
Comparison 14: TXA IV vs desmopressin, Outcome 3: Risk of experiencing DVT
14.4
14.4. Analysis
Comparison 14: TXA IV vs desmopressin, Outcome 4: Risk of experiencing PE
15.1
15.1. Analysis
Comparison 15: TXA IV vs fibrin topical, Outcome 1: Risk of allogeneic blood transfusion
15.2
15.2. Analysis
Comparison 15: TXA IV vs fibrin topical, Outcome 2: All‐cause mortality
15.3
15.3. Analysis
Comparison 15: TXA IV vs fibrin topical, Outcome 3: Units of red blood cells transfused
15.5
15.5. Analysis
Comparison 15: TXA IV vs fibrin topical, Outcome 5: Risk of experiencing DVT
15.6
15.6. Analysis
Comparison 15: TXA IV vs fibrin topical, Outcome 6: Risk of experiencing PE
16.1
16.1. Analysis
Comparison 16: TXA topical vs fibrin topical, Outcome 1: Risk of allogeneic blood transfusion
16.2
16.2. Analysis
Comparison 16: TXA topical vs fibrin topical, Outcome 2: All‐cause mortality
16.3
16.3. Analysis
Comparison 16: TXA topical vs fibrin topical, Outcome 3: Reoperation
16.4
16.4. Analysis
Comparison 16: TXA topical vs fibrin topical, Outcome 4: Length of hospital stay
16.5
16.5. Analysis
Comparison 16: TXA topical vs fibrin topical, Outcome 5: Risk of experiencing DVT
16.6
16.6. Analysis
Comparison 16: TXA topical vs fibrin topical, Outcome 6: Risk of experiencing PE
16.7
16.7. Analysis
Comparison 16: TXA topical vs fibrin topical, Outcome 7: Risk of experiencing CVA
17.1
17.1. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 1: Risk of allogeneic blood transfusion
17.2
17.2. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 2: All‐cause mortality
17.3
17.3. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 3: Units of red blood cells transfused
17.4
17.4. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 4: Reoperation
17.5
17.5. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 5: Length of hospital stay
17.6
17.6. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 6: Risk of experiencing DVT
17.7
17.7. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 7: Risk of experiencing PE
17.8
17.8. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 8: Risk of experiencing MI
17.9
17.9. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 9: Risk of experiencing CVA
17.10
17.10. Analysis
Comparison 17: Aprotinin vs placebo, Outcome 10: Risk of suspected serious drug reactions
18.1
18.1. Analysis
Comparison 18: EACA vs placebo, Outcome 1: Risk of allogeneic blood transfusion
18.2
18.2. Analysis
Comparison 18: EACA vs placebo, Outcome 2: Units of red blood cells transfused
18.3
18.3. Analysis
Comparison 18: EACA vs placebo, Outcome 3: Reoperation
18.4
18.4. Analysis
Comparison 18: EACA vs placebo, Outcome 4: Risk of experiencing DVT
18.5
18.5. Analysis
Comparison 18: EACA vs placebo, Outcome 5: Risk of experiencing PE
18.6
18.6. Analysis
Comparison 18: EACA vs placebo, Outcome 6: Risk of experiencing MI
18.7
18.7. Analysis
Comparison 18: EACA vs placebo, Outcome 7: Risk of experiencing CVA
19.1
19.1. Analysis
Comparison 19: EACA vs aprotinin, Outcome 1: Risk of allogeneic blood transfusion
19.2
19.2. Analysis
Comparison 19: EACA vs aprotinin, Outcome 2: Reoperation
19.3
19.3. Analysis
Comparison 19: EACA vs aprotinin, Outcome 3: Risk of experiencing DVT
19.4
19.4. Analysis
Comparison 19: EACA vs aprotinin, Outcome 4: Risk of experiencing PE
20.1
20.1. Analysis
Comparison 20: Desmopressin vs placebo, Outcome 1: All‐cause mortality
20.2
20.2. Analysis
Comparison 20: Desmopressin vs placebo, Outcome 2: Units of red blood cells transfused
20.3
20.3. Analysis
Comparison 20: Desmopressin vs placebo, Outcome 3: Risk of experiencing DVT
20.4
20.4. Analysis
Comparison 20: Desmopressin vs placebo, Outcome 4: Risk of experiencing PE
20.5
20.5. Analysis
Comparison 20: Desmopressin vs placebo, Outcome 5: Risk of experiencing MI
20.6
20.6. Analysis
Comparison 20: Desmopressin vs placebo, Outcome 6: Risk of suspected serious drug reactions
20.7
20.7. Analysis
Comparison 20: Desmopressin vs placebo, Outcome 7: Length of hospital stay
21.1
21.1. Analysis
Comparison 21: Fibrin topical vs placebo, Outcome 1: Risk of allogeneic blood transfusion
21.2
21.2. Analysis
Comparison 21: Fibrin topical vs placebo, Outcome 2: All‐cause mortality
21.3
21.3. Analysis
Comparison 21: Fibrin topical vs placebo, Outcome 3: Reoperation
21.4
21.4. Analysis
Comparison 21: Fibrin topical vs placebo, Outcome 4: Length of hospital stay
21.5
21.5. Analysis
Comparison 21: Fibrin topical vs placebo, Outcome 5: Risk of experiencing DVT
21.6
21.6. Analysis
Comparison 21: Fibrin topical vs placebo, Outcome 6: Risk of experiencing PE
21.7
21.7. Analysis
Comparison 21: Fibrin topical vs placebo, Outcome 7: Risk of experiencing CVA
22.1
22.1. Analysis
Comparison 22: TXA IV + TXA oral vs TXA IV, Outcome 1: Risk of allogeneic blood transfusion
22.2
22.2. Analysis
Comparison 22: TXA IV + TXA oral vs TXA IV, Outcome 2: All‐cause mortality
22.3
22.3. Analysis
Comparison 22: TXA IV + TXA oral vs TXA IV, Outcome 3: Reoperation
22.4
22.4. Analysis
Comparison 22: TXA IV + TXA oral vs TXA IV, Outcome 4: Length of hospital stay
22.5
22.5. Analysis
Comparison 22: TXA IV + TXA oral vs TXA IV, Outcome 5: Risk of experiencing DVT
22.6
22.6. Analysis
Comparison 22: TXA IV + TXA oral vs TXA IV, Outcome 6: Risk of experiencing PE
23.1
23.1. Analysis
Comparison 23: TXA IV + TXA topical vs TXA IV, Outcome 1: Risk of allogeneic blood transfusion
23.2
23.2. Analysis
Comparison 23: TXA IV + TXA topical vs TXA IV, Outcome 2: Length of hospital stay
23.3
23.3. Analysis
Comparison 23: TXA IV + TXA topical vs TXA IV, Outcome 3: Risk of experiencing DVT
23.4
23.4. Analysis
Comparison 23: TXA IV + TXA topical vs TXA IV, Outcome 4: Risk of experiencing PE
23.5
23.5. Analysis
Comparison 23: TXA IV + TXA topical vs TXA IV, Outcome 5: Risk of experiencing CVA
24.1
24.1. Analysis
Comparison 24: TXA IV + TXA topical vs TXA oral, Outcome 1: Risk of allogeneic blood transfusion
24.2
24.2. Analysis
Comparison 24: TXA IV + TXA topical vs TXA oral, Outcome 2: Length of hospital stay
24.3
24.3. Analysis
Comparison 24: TXA IV + TXA topical vs TXA oral, Outcome 3: Risk of experiencing DVT
24.4
24.4. Analysis
Comparison 24: TXA IV + TXA topical vs TXA oral, Outcome 4: Risk of experiencing PE
24.5
24.5. Analysis
Comparison 24: TXA IV + TXA topical vs TXA oral, Outcome 5: Risk of experiencing CVA
25.1
25.1. Analysis
Comparison 25: TXA IV + TXA topical vs TXA topical, Outcome 1: Risk of allogeneic blood transfusion
26.1
26.1. Analysis
Comparison 26: TXA topical vs TXA oral + TXA topical, Outcome 1: Risk of allogeneic blood transfusion
26.2
26.2. Analysis
Comparison 26: TXA topical vs TXA oral + TXA topical, Outcome 2: All‐cause mortality
26.3
26.3. Analysis
Comparison 26: TXA topical vs TXA oral + TXA topical, Outcome 3: Length of hospital stay
26.4
26.4. Analysis
Comparison 26: TXA topical vs TXA oral + TXA topical, Outcome 4: Risk of experiencing DVT
26.5
26.5. Analysis
Comparison 26: TXA topical vs TXA oral + TXA topical, Outcome 5: Risk of experiencing PE
26.6
26.6. Analysis
Comparison 26: TXA topical vs TXA oral + TXA topical, Outcome 6: Risk of experiencing MI
26.7
26.7. Analysis
Comparison 26: TXA topical vs TXA oral + TXA topical, Outcome 7: Risk of experiencing CVA
27.1
27.1. Analysis
Comparison 27: TXA oral vs TXA combined topical + IV + oral, Outcome 1: Risk of allogeneic blood transfusion
27.2
27.2. Analysis
Comparison 27: TXA oral vs TXA combined topical + IV + oral, Outcome 2: Length of hospital stay
27.3
27.3. Analysis
Comparison 27: TXA oral vs TXA combined topical + IV + oral, Outcome 3: Risk of experiencing DVT
28.1
28.1. Analysis
Comparison 28: TXA IV + topical lower dose vs TXA IV + topical higher dose, Outcome 1: Risk of allogeneic blood transfusion
28.2
28.2. Analysis
Comparison 28: TXA IV + topical lower dose vs TXA IV + topical higher dose, Outcome 2: Length of hospital stay
28.3
28.3. Analysis
Comparison 28: TXA IV + topical lower dose vs TXA IV + topical higher dose, Outcome 3: Risk of experiencing DVT
28.4
28.4. Analysis
Comparison 28: TXA IV + topical lower dose vs TXA IV + topical higher dose, Outcome 4: Risk of experiencing PE
28.5
28.5. Analysis
Comparison 28: TXA IV + topical lower dose vs TXA IV + topical higher dose, Outcome 5: Risk of experiencing MI
28.6
28.6. Analysis
Comparison 28: TXA IV + topical lower dose vs TXA IV + topical higher dose, Outcome 6: Risk of experiencing CVA
29.1
29.1. Analysis
Comparison 29: TXA oral + topical lower dose vs TXA oral + topical higher dose, Outcome 1: Risk of allogeneic blood transfusion
29.2
29.2. Analysis
Comparison 29: TXA oral + topical lower dose vs TXA oral + topical higher dose, Outcome 2: All‐cause mortality
29.3
29.3. Analysis
Comparison 29: TXA oral + topical lower dose vs TXA oral + topical higher dose, Outcome 3: Length of hospital stay
29.4
29.4. Analysis
Comparison 29: TXA oral + topical lower dose vs TXA oral + topical higher dose, Outcome 4: Risk of experiencing DVT
29.5
29.5. Analysis
Comparison 29: TXA oral + topical lower dose vs TXA oral + topical higher dose, Outcome 5: Risk of experiencing PE
29.6
29.6. Analysis
Comparison 29: TXA oral + topical lower dose vs TXA oral + topical higher dose, Outcome 6: Risk of experiencing MI
29.7
29.7. Analysis
Comparison 29: TXA oral + topical lower dose vs TXA oral + topical higher dose, Outcome 7: Risk of experiencing CVA
30.1
30.1. Analysis
Comparison 30: TXA IV + TXA, oral days 1 to 2 vs TXA IV + TXA, oral days 1 to 5, Outcome 1: Risk of allogeneic blood transfusion
30.2
30.2. Analysis
Comparison 30: TXA IV + TXA, oral days 1 to 2 vs TXA IV + TXA, oral days 1 to 5, Outcome 2: Risk of experiencing DVT
30.3
30.3. Analysis
Comparison 30: TXA IV + TXA, oral days 1 to 2 vs TXA IV + TXA, oral days 1 to 5, Outcome 3: Risk of experiencing PE
31.1
31.1. Analysis
Comparison 31: TXA, IV + TXA, IV vs TXA, IV + placebo, Outcome 1: Risk of allogeneic blood transfusion
31.2
31.2. Analysis
Comparison 31: TXA, IV + TXA, IV vs TXA, IV + placebo, Outcome 2: Risk of experiencing MI
31.3
31.3. Analysis
Comparison 31: TXA, IV + TXA, IV vs TXA, IV + placebo, Outcome 3: Risk of experiencing CVA
31.4
31.4. Analysis
Comparison 31: TXA, IV + TXA, IV vs TXA, IV + placebo, Outcome 4: Risk of experiencing DVT
31.5
31.5. Analysis
Comparison 31: TXA, IV + TXA, IV vs TXA, IV + placebo, Outcome 5: Risk of experiencing PE
32.1
32.1. Analysis
Comparison 32: TXA, IV + TXA, IV vs placebo, Outcome 1: Risk of allogeneic blood transfusion
32.2
32.2. Analysis
Comparison 32: TXA, IV + TXA, IV vs placebo, Outcome 2: Risk of experiencing MI
32.3
32.3. Analysis
Comparison 32: TXA, IV + TXA, IV vs placebo, Outcome 3: Risk of experiencing CVA
32.4
32.4. Analysis
Comparison 32: TXA, IV + TXA, IV vs placebo, Outcome 4: Risk of experiencing DVT
32.5
32.5. Analysis
Comparison 32: TXA, IV + TXA, IV vs placebo, Outcome 5: Risk of experiencing PE
33.1
33.1. Analysis
Comparison 33: TXA IV + placebo vs placebo, Outcome 1: Risk of allogeneic blood transfusion
33.2
33.2. Analysis
Comparison 33: TXA IV + placebo vs placebo, Outcome 2: Risk of experiencing MI
33.3
33.3. Analysis
Comparison 33: TXA IV + placebo vs placebo, Outcome 3: Risk of experiencing CVA
33.4
33.4. Analysis
Comparison 33: TXA IV + placebo vs placebo, Outcome 4: Risk of experiencing DVT
33.5
33.5. Analysis
Comparison 33: TXA IV + placebo vs placebo, Outcome 5: Risk of experiencing PE
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013295

References

References to studies included in this review

Alvarez 2008 {published data only}
    1. Alvarez JC, Santiveri FX, Ramos I, Vela E, Puig L, Escolano F. Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a blood conservation program is applied. Transfusion 2008;48(3):519-25. - PubMed
Alvarez 2019 hip {published data only}
    1. Alvarez J, Santiveri FJ, Ramos MI, Gallart L, Aguilera L, Puig-Verdie L. Clinical trial on the effect of tranexamic acid on bleeding and fibrinolysis in primary hip and knee replacement. Revista Espanola De Anestesiologia Y Reanimacion 2019;66(6):299-306. - PubMed
Alvarez 2019 knee {published data only}
    1. Alvarez J, Santiveri FJ, Ramos MI, Gallart L, Aguilera L, Puig-Verdie L. Clinical trial on the effect of tranexamic acid on bleeding and fibrinolysis in primary hip and knee replacement. Revista Espanola De Anestesiologia Y Reanimacion 2019;66(6):299-306. - PubMed
Benoni 1996 {published data only}
    1. Benoni G, Fredin H. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: A prospective, randomised, double-blind study of 86 patients. Journal of Bone and Joint Surgery 1996;78(3):434-40. - PubMed
Benoni 2000 {published data only}
    1. Benoni G, Lethagen S, Nilsson P, Fredin H. Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty. Acta Orthopaedica Scandinavica 2000;71(3):250-4. - PubMed
Benoni 2001 {published data only}
    1. Benoni G, Fredin H, Knebel R, Nilsson P. Blood conservation with tranexamic acid in total hip arthroplasty: a randomized, double-blind study in 40 primary operations. Acta Orthopaedica Scandinavica 2001;72(5):442-8. - PubMed
Boese 2017 {published data only}
    1. Boese CK, Centeno L, Walters RW. Blood conservation using tranexamic acid is not superior to epsilon-aminocaproic acid after total knee arthroplasty. Journal of Bone and Joint Surgery 2017;99(19):1621-8. - PubMed
    1. NCT01873768. Clinical efficacy of tranexamic acid and ε-aminocaproic acid in reducing blood loss following total knee replacement. www.clinicaltrials.gov/ct2/show/NCT01873768 (first received 6 June 2013).
Bradley 2019 hip {published data only}
    1. Bradley KE, Ryan SP, Penrose CT, Grant SA, Wellman SS, Attarian DE, et al. Tranexamic acid or epsilon-aminocaproic acid in total joint arthroplasty? A randomized controlled trial. The Bone & Joint Journal 2019;101-b(9):1093-9. - PubMed
    1. NCT02030821. TXA vs. amicar in total knee and hip arthroplasty. clinicaltrials.gov/ct2/show/NCT02030821 (first received 6 January 2018).
Bradley 2019 knee {published data only}
    1. Bradley KE, Ryan SP, Penrose CT, Grant SA, Wellman SS, Attarian DE, et al. Tranexamic acid or epsilon-aminocaproic acid in total joint arthroplasty? A randomized controlled trial. Journal of Bone and Joint Surgery. American Volume 2019;101-b(9):1093-9. - PubMed
    1. NCT02030821. TXA vs. Amicar in total knee and hip arthroplasty. clinicaltrials.gov/ct2/show/NCT02030821 (first received 6 January 2014).
Camarasa 2006 {published data only}
    1. Camarasa MA, Olle G, Serra-Prat M, Martin A, Sanchez M, Ricos P, et al. Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. British Journal of Anaesthesia 2006;96(5):576-82. - PubMed
Cao 2018 {published data only}
    1. Cao G, Huang Q, Huang Z, Zhang S, Luo Z, Lei Y, et al. The efficacy and safety of multiple-dose oral tranexamic acid on blood loss following total hip arthroplasty: a randomized controlled trial. International Orthopaedics 2018;10:10. - PubMed
Chang 2022 {published data only}
    1. Chang MJ, Shin JY, Yoon C, Kim TW, Chang CB, Kang SB. Effect of sequential intravenous and oral tranexamic acid on hemoglobin drop after total knee arthroplasty: a randomized controlled trial. Journal of Bone and Joint Surgery. American Volume 2022;104(2):154-9. - PubMed
    1. NCT03109652. Serial use of intravenous and oral tranexamic acid in primary total knee arthroplasty patients. clinicaltrials.gov/ct2/show/NCT03109652 (first received 12 April 2017).
Chin 2020 {published data only}
    1. Chin J, Blackett J, Kieser DC, Frampton C, Hooper G. The value of routine intravenous tranexamic acid in total hip arthroplasty: a preliminary study. Advances in Orthopaedics 2020;2020:2943827. - PMC - PubMed
Claeys 2007 {published data only}
    1. Claeys MA, Vermeersch N, Haentjens P. Reduction of blood loss with tranexamic acid in primary total hip replacement surgery. Acta Chirurgica Belgica 2007;107(4):397-401. - PubMed
Clave 2019 {published data only}
    1. Clavé A, Gérard R, Lacroix J, Baynat C, Danguy des Déserts M, Gatineau F, et al. A randomized, double-blind, placebo-controlled trial on the efficacy of tranexamic acid combined with rivaroxaban thromboprophylaxis in reducing blood loss after primary cementless total hip arthroplasty. The Bone and Joint Journal 2019;101-b(2):207-12. - PubMed
    1. NCT02403596. Blood-sparing during hip prosthesis surgery with Exacyl® in patients treated with rivaroxaban. clinicaltrials.gov/ct2/show/NCT02403596 (first received 13 March 2015).
Colwell 2007 {published data only}
    1. Colwell CW Jr, Chelly JE, Murkin JM, Stevens D, O'Keefe TJ, Hall R, et al. Randomized study of aprotinin effect on transfusions and blood loss in primary THA. Clinical Orthopaedics and Related Research 2007;465:189-95. - PubMed
    1. Colwell CW, Chelly JE, Stevens DG, O'Keefe TJ, Hall R, Parvizi J. Effect of aprotinin on transfusion and blood loss in elective primary total hip arthroplasty (THA). In: American Academy of Orthopaedic Surgeons Annual Meeting. 2007:242.
    1. Colwell CW, Jacques CE, Stevens DG, O'Keefe TJ, Hall RI, Parvizi J, et al. Effect of aprotinin on transfusion requirements and blood loss in elective primary total hip arthroplasty (THA). European Federation of National Associations of Orthopaedics and Traumatology 2009;91‐B(Suppl I):103‐10a.
Compostella 1997 {published data only}
    1. Compostella FA, Marcante P, Marcante S, Dosso P. High dose aprotinin in elective total hip replacement surgery: effects on bleeding and renal function. Metabolism, Nutrition, Endocrinology 1997;78(Suppl 1):66.
Cui 2019 {published data only}
    1. ChiCTR-IOR-17013861. The efficacy and safety of multiple high-dose intravenous tranexamic acid in peri-operative period of total hip/knee arthroplasty under the management of enhanced recovery after surgery: a prospective, randomized, controlled study. www.chictr.org.cn/showprojen.aspx?proj=23861 2017.
    1. Cui D, Lei Y, Xu H, Huang Q, Pei F. Efficacy and safety of a loading high-dose tranexamic acid followed by postoperative five doses in total hip arthroplasty: a randomized controlled trial. Chinese Journal of Reparative & Reconstructive Surgery 2019;33(8):935-9. - PMC - PubMed
D'Ambrosio 1999 {published data only}
    1. D'Ambrosio A, Borghi B, Damato A, D'Amato G, Antonacci D, Valeri F. Reducing perioperative blood loss in patients undergoing total hip arthroplasty. International Journal of Artificial Organs 1999;22(1):47-51. - PubMed
Dorji 2021 {published data only}
    1. CTRI/2018/05/014106. To compare the effect of use of both intravenous and intra articular injection of tranexamic acid with only intra-articular injection of tranexamic acid in reducing blood loss in total knee replacement patients in western India. ctri.nic.in/Clinicaltrials/advsearch.php 2018.
    1. Dorji Y, Singh CM, Mishra AK, Sud AD. Efficacy of combined use of intravenous and intra-articular versus intra-articular tranexemic acid in blood loss in primary total knee arthroplasty: a randomized controlled study. Journal of Arthroscopy and Joint Surgery 2021;8(2):134-8.
Ekback 2000 {published data only}
    1. Ekback G, Axelsson K, Ryttberg L, Edlund B, Kjellberg J, Weckstrom J, et al. Tranexamic acid reduces blood loss in total hip replacement surgery. Anesthesia and Analgesia 2000;91(5):1124-30. - PubMed
Ellis 2001 {published data only}
    1. Ellis MH, Fredman B, Zohar E, Ifrach N, Jedeikin R. The effect of tourniquet application, tranexamic acid, and desmopressin on the procoagulant and fibrinolytic systems during total knee replacement. Journal of Clinical Anesthesia 2001;13(7):509-13. - PubMed
    1. Zohar E, Fredman B, Ellis MH, Ifrach N, Stern A, Jedeikin R. A comparative study of the postoperative allogeneic blood-sparing effects of tranexamic acid and of desmopressin after total knee replacement. Transfusion 2001;41(10):1285-9. - PubMed
Engel 2001 {published data only}
    1. Engel JM, Hohaus T, Ruwoldt R, Menges T, Jurgensen I, Hempelmann G. Regional hemostatic status and blood requirements after total knee arthroplasty with and without tranexamic acid or aprotinin. Anesthesia and Analgesia 2001;92(3):775-80. - PubMed
Flordal 1992 {published data only}
    1. Flordal PA, Ljungstrom KG, Ekman B, Neander G. Effects of desmopressin on blood loss in hip arthroplasty. Controlled study in 50 patients. Acta Orthopaedica Scandinavica 1992;63(4):381-5. - PubMed
    1. Flordal PA, Ljungstrom KG, Svensson J, Ekman B, Neander G. Effects on coagulation and fibrinolysis of desmopressin in patients undergoing total hip replacement. Thrombosis and Haemostasis 1991;66(6):652-6. - PubMed
Garcia Enguita 1998 {published data only}
    1. Garcia-Enguita MA, Ortega JP, Gomez C, Rasal S, Pascual A, Urieta-Solanas A. High dose aprotinin in complex total hip arthroplasty. Transfusion and Haemostasis 1998;80(Suppl 1):A270.
Garneti 2004 {published data only}
    1. Garneti N, Field J. Bone bleeding during total hip arthroplasty after administration of tranexamic acid. Journal of Arthroplasty 2004;19(4):488-92. - PubMed
Georgiadis 2013 {published data only}
    1. Georgiadis AG, Muh S, Weir RM, Silverton C, Laker MW. Topical tranexamic acid in total knee arthroplasty: a double-blind, randomized placebo controlled trial. In: American Academy of Orthopaedic Surgeons Annual Meeting. Vol. Paper 433. 2013.
    1. Georgiadis AG, Muh SJ, Silverton CD, Weir RM, Laker MW. A prospective double-blind placebo controlled trial of topical tranexamic acid in total knee arthroplasty. Journal of Arthroplasty 2013;28(Suppl 1):78-82. - PubMed
    1. NCT01370460. Topical tranexamic acid and acute blood loss in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT01370460 (first received 3 June 2011).
Gill 2009 {published data only}
    1. Gill JB, Chase E, Rosenstein AD. The use of tranexamic acid in revision total hip arthroplasty: a pilot study. Current Orthopaedic Practice 2009;20(2):152-6.
Gomez Barrena 2014 {published data only}
    1. 2011-003218-17. Efficacy of topical tranexamic acid versus intravenous administration to reduce blood transfusion rate in total knee arthroplasty surgery: phase III, unicentric, controlled, double-blind, randomized non-inferiority clinical trial. clinicaltrialsregister.eu/ctr-search/search?query=2011-003218-17 (first received 12 July 2011).
    1. Gomez-Barrena E, Ortega-Andreu M, Padilla-Eguiluz NG, Perez-Chrzanowska H, Figueredo-Zalve R. Topical intra-articular compared with intravenous tranexamic acid to reduce blood loss in primary total knee replacement: a double-blind, randomized, controlled, noninferiority clinical trial. Journal of bone and Joint Surgery 2014;96(23):1937-44. - PubMed
Gonzalez Osuna 2021 {published data only}
    1. Gonzalez Osuna A, Rojas LF, Lamas C, Aguilera Roig X, Pla-Junca F, Videla S, et al. Population pharmacokinetics of intra-articular and intravenous administration of tranexamic acid in patients undergoing total knee replacement. Clinical Pharmacokinetics 2021;61:83-95. - PubMed
Good 2003 {published data only}
    1. Good L, Peterson E, Lisander B. Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. British Journal of Anaesthesia 2003;90(5):596-9. - PubMed
Goyal 2017 {published data only}
    1. ACTRN12614000582651. Comparison of different modes of tranexamic acid administration in patients undergoing total knee arthroplasty. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366396 (first received 23 May 2014).
    1. Goyal N, Chen DB, Harris IA, Rowden NJ, Kirsh G, MacDessi SJ. Intravenous vs intra-articular tranexamic acid in total knee arthroplasty: a randomized, double-blind trial. Journal of Arthroplasty 2016;32(1):28-32. [WEBSITE: https://www.arthroplastyjournal.org/article/S0883-5403(16)30359-X/fulltext] - PubMed
    1. Goyal N, Chen DB, Harris IA, Rowden NJ, Kirsh G, MacDessi SJ. Intravenous vs intra-articular tranexamic acid in total knee arthroplasty: a randomized, double-blind trial. Journal of Arthroplasty 2017;32(1):28-32. - PubMed
    1. Macdessi S, Chen D, Goyal N, Harris I, Kirsh G, Rowden N. Intravenous versus intra-articular tranexamic acid in patients undergoing primary unilateral total knee arthroplasty: A prospective randomized double blinded non-inferiority trial. Orthopaedic Journal of Sports Medicine 2016;4(2 Suppl 1):1.
Harley 2002 {published data only}
    1. Harley BJ, Beaupre LA, Cinats JG, Guenther CR, Jones CA. The effect of epsilon aminocaproic acid on blood loss in patients who undergo primary total hip replacement surgery. Journal of Bone and Joint Surgery 2001;83‐B(Suppl 1):21. - PMC - PubMed
    1. Harley BJ, Beaupre LA, Jones CA, Cinats JG, Guenther CR. The effect of epsilon aminocaproic acid on blood loss in patients who undergo primary total hip replacement: a pilot study. Canadian Journal of Surgery 2002;45(3):185-90. - PMC - PubMed
Hayes 1996 {published data only}
    1. Hayes A, Murphy DB, McCarroll M. The efficacy of single-dose aprotinin 2 million kiu in reducing blood loss and its impact on the incidence of deep venous thrombosis in patients undergoing total hip replacement surgery. Journal of Clinical Anesthesia 1996;8(5):357-60. - PubMed
Hiippala 1995 {published data only}
    1. Hiippala S, Strid L, Wennerstrand M, Arvela V, Mantyla S, Ylinen J, et al. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. British Journal of Anaesthesia 1995;74(5):534-7. - PubMed
Hiippala 1997 {published data only}
    1. Hiippala ST, Strid LJ, Wennerstrand MI, Arvela JV, Niemela HM, Mantyla SK, et al. Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty. Anesthesia and Analgesia 1997;84(4):839-44. - PubMed
Husted 2003 {published data only}
    1. Husted H, Blond L, Sonne-Holm S, Holm G, Jacobsen TW, Gebuhr P. Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients. Acta Orthopaedica Scandinavica 2003;74(6):665-9. - PubMed
Jansen 1999 {published data only}
    1. Jansen AJ, Andreica S, Claeys M, D'Haese J, Camu F, Jochmans K. Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty. British Journal of Anaesthesia 1999;83(4):596-601. - PubMed
    1. Sorin A, Claeys MA, Jansen A, D'Haese J, Camu F. Reduction of blood loss by tranexamic acid in total knee replacement. Journal of Bone and Joint Surgery 1999;81‐B(Suppl II):234.
Janssens 1994 {published data only}
    1. Janssens M, Joris J, David JL, Lemaire R, Lamy M. High-dose aprotinin reduces blood loss in patients undergoing total hip replacement surgery. Anesthesiology 1994;80(1):23-9. - PubMed
Jeserschek 2003 {published data only}
    1. Jeserschek R, Clar H, Aigner C, Rehak P, Primus B, Windhager R. Reduction of blood loss using high-dose aprotinin in major orthopaedic surgery: a prospective, double-blind, randomised and placebo-controlled study. Journal of Bone and Joint Surgery 2003;85(2):174-7. - PubMed
Johansson 2005 {published data only}
    1. Johansson T, Pettersson LG, Lisander B. Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients. Acta Orthopaedica 2005;76(3):314-9. - PubMed
Jules‐Elysee 2019 {published data only}
    1. Jules-Elysee KM, Tseng A, Sculco TP, Baaklini LR, McLawhorn AS, Pickard AJ, et al. Comparison of topical and intravenous tranexamic acid for total knee replacement: a randomized double-blinded controlled study of effects on tranexamic acid levels and thrombogenic and inflammatory marker levels. Journal of Bone and Joint Surgery. American Volume 2019;101(23):2120-8. - PMC - PubMed
    1. NCT02540226. Effect of topical and intravenous tranexamic acid (TXA) on thrombogenic markers in patients undergoing knee replacement. clinicaltrials.gov/ct2/show/NCT02540226 (first received 1 September 2015).
Kakar 2009 Bilateral TKR {published data only}
    1. Kakar PN, Gupta N, Govil P, Shah V. Efficacy and safety of tranexamic acid in control of bleeding following TKR: a randomized clinical trial. Indian Journal of Anaesthesia 2009;53(6):667-71. - PMC - PubMed
Kakar 2009 Unilateral TKR {published data only}
    1. Kakar PN, Gupta N, Govil P, Shah V. Efficacy and safety of tranexamic acid in control of bleeding following TKR: a randomized clinical trial. Indian Journal of Anaesthesia 2009;53(6):667-71. - PMC - PubMed
Kang 2021a {published data only}
    1. ChiCTR1900025013. Clinical observation of multiple dose use of tranexamic acid in patients with rheumatoid arthritis after total knee arthroplasty. www.chictr.org.cn/com/25/showprojen.aspx?proj=41375 2019.
    1. Kang BX, Xu H, Gao CX, Zhong S, Zhang J, Xie J, et al. Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study. BMC Musculoskeletal Disorders 2021;22(1):425. - PMC - PubMed
    1. Kang BX, Xu H, Gao X, Zhong S, Zhang J, Xie J, et al. Multiple-dose tranexamic acid for perioperative blood loss in total knee arthroplasty in patients with rheumatoid arthritis: a single-blinded, randomised, parallel-controlled study protocol in China. BMJ Open 2020;10(8):e034431. - PMC - PubMed
Kang 2021b {published data only}
    1. ChiCTR1900022737. Clinical observation for multiple use of tranexamic acid after total knee arthroplasty. www.chictr.org.cn/showproj.aspx?proj=38007 (first received 24 April 2019).
    1. Kang BX, Li YL, Xu H, Gao CX, Zhong S, Zhang J, et al. Effect of multiple doses of intravenous tranexamic acid on perioperative blood loss in total knee arthroplasty: a randomized controlled study. Orthopaedic Audio-Synopsis Continuing Medical Education 2021;13(1):126-33. - PMC - PubMed
Karnezis 1994 hip {published data only}
    1. Karnezis TA, Stulberg SD, Wixson RL, Reilly P. The hemostatic effects of desmopressin on patients who had total joint arthroplasty. A double-blind randomized trial. Journal of Bone and Joint Surgery. American Volume 1994;76(10):1545-50. - PubMed
Karnezis 1994 knee {published data only}
    1. Karnezis TA, Stulberg SD, Wixson RL, Reilly P. The hemostatic effects of desmopressin on patients who had total joint arthroplasty. A double-blind randomized trial. Journal of Bone and Joint Surgery. American Volume 1994;76(10):1545-50. - PubMed
Kayupov 2017a {published data only}
    1. Fillingham YA, Kayupov E, Plummer DR, Moric M, Gerlinger TL, Della Valle CJ. The James A. Rand young investigator's award: a randomized controlled trial of oral and intravenous tranexamic acid in total knee arthroplasty: The same efficacy at lower cost? Journal of Arthroplasty 2016;31(9 Suppl):26-30. - PubMed
Kayupov 2017b {published data only}
    1. Kayupov E, Fillingham YA, Okroj K, Plummer DR, Moric M, Gerlinger TL, et al. Oral and intravenous tranexamic acid are equivalent at reducing blood loss following total hip arthroplasty: a randomized controlled trial. Journal of Bone and Joint Surgery. American Volume 2017;99(5):373-8. - PubMed
    1. NCT02233101. Oral vs. intravenous TXA study proposal. clinicaltrials.gov/ct2/show/NCT02233101 (first received 26 June 2014).
King 2019 {published data only}
    1. King L, Randle R, Dare W, Bernaitis N. Comparison of oral vs. combined topical/intravenous/oral tranexamic acid in the prevention of blood loss in total knee arthroplasty: a randomised clinical trial. Orthopaedics & Traumatology, Surgery & Research 2019;105(6):1073-7. - PubMed
Langdown 2000 {published data only}
    1. Langdown AJ, Field J, Grote J, Himayat H. Aprotinin (Trasylol) does not reduce bleeding in primary total hip arthroplasty. Journal of Arthroplasty 2000;15(8):1009-12. - PubMed
Lei 2017 {published data only}
    1. Lei Y, Xie J, Xu B, Xie X, Huang Q, Pei F. The efficacy and safety of multiple-dose intravenous tranexamic acid on blood loss following total knee arthroplasty: a randomized controlled trial. International Orthopaedics 2017;41(10):2053-9. - PubMed
Lei 2018 {published data only}
    1. Lei Y, Huang Q, Huang Z, Xie J, Chen G, Pei F. Multiple-dose intravenous tranexamic acid further reduces hidden blood loss after total hip arthroplasty: a randomized controlled trial. Journal of Arthroplasty 2018;33(9):2940-5. - PubMed
Lei 2020 {published data only}
    1. ChiCTR-INR-16009288. Multi-bolus of IV-TXA to reduce hidden blood loss and inflammatory response in ERAS total hip and knee arthroplasty: a randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=15741 2016.
    1. Lei Y, Xie J, Huang Q, Huang W, Pei F. Additional benefits of multiple-dose tranexamic acid to anti-fibrinolysis and anti-inflammation in total knee arthroplasty: a randomized controlled trial. Archives of Orthopaedic and Trauma Surgery 2020;140(8):1087-95. - PubMed
Lemay 2004 {published data only}
    1. Lemay E, Guay J, Cote C, Roy A. Tranexamic acid reduces the need for allogenic red blood cell transfusions in patients undergoing total hip replacement. Canadian Journal of Anesthesia 2004;51(1):31-7. - PubMed
Levine 2014 {published data only}
    1. Levine BR, Haughom BD, Belkin MN, Goldstein ZH. Weighted versus uniform dose of tranexamic acid in patients undergoing primary, elective knee arthroplasty: a prospective randomized controlled trial. Journal of Arthroplasty 2014;29(9 Suppl):186-8. - PubMed
    1. NCT01651806. Weighted versus uniform dose of tranexamic acid in patients undergoing primary, knee arthroplasty. clinicaltrials.gov/ct2/show/NCT01651806 (first received 1 May 2012).
Llau 1998 {published data only}
    1. Llau JV, Aguilar G, Soliveres J, Minguez MF, Saz T, Belda FJ. Aprotinin administration reduces blood loss and transfusion requirements in patients undergoing total hip arthroplasty. Transfusion and Haemostasis 1998;80(Suppl 1):A271.
Lopez Picado 2017 {published data only}
    1. Barrachina B, Lopez-Picado A, Remon M, Fondarella A, Iriarte I, Bastida R, et al. Tranexamic acid compared with placebo for reducing total blood loss in hip replacement surgery: a randomized clinical trial. Anesthesia and Analgesia 2016;122(4):986-95. - PubMed
    1. Lopez-Picado A, Albinarrate A, Barrachina B. Determination of perioperative blood loss: accuracy or approximation? Anesthesia and Analgesia 2017;125(1):280-6. - PubMed
    1. NCT01199627. Tranexamic acid versus placebo for the reduction of blood loss in total hip replacement surgery. clinicaltrials.gov/ct2/show/NCT01199627 (first received 7 September 2010).
Luo 2022 {published data only}
    1. ChiCTR1900020498. Efficacy of tranexamic acid combined with carbazochrome sodium sulfonate on blood loss in primary total hip arthroplasty using a direct anterior approach: a prospective randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=34656 2019.
    1. Luo Y, Releken Y, Yang D, Yue Y, Liu Z, Kang P. Effects of carbazochrome sodium sulfonate combined with tranexamic acid on hemostasis and inflammation during perioperative period of total hip arthroplasty: a randomized controlled trial. Orthopaedics & Traumatology: Surgery & Research 2022;108(1):103092. - PubMed
Molloy 2007 {published data only}
    1. Molloy DO, Archbold HA, Ogonda L, McConway J, Wilson RK, Beverland DE. Comparison of topical fibrin spray and tranexamic acid on blood loss after total knee replacement: a prospective, randomised controlled trial. Journal of Bone and Joint Surgery 2007;89(3):306-9. - PubMed
    1. Molloy DO, McConway J, Archbold HAP, Ogonda L, Beverland MDE. Comparison of tranexamic acid and topical fibrin spray on blood loss following total knee arthroplasty, a randomised controlled trial. Orthopaedic Proceedings 2008;90‐B(Suppl II):320.
Morales‐Avalos 2021 {published data only}
    1. Morales-Avalos R, Ramos-Morales T, Garcia-Pedro JA, Espinoza-Galindo AM, Acosta-Olivo C, Morcos-Sandino M, et al. Tranexamic acid versus aminocaproic acid in multiple doses via the oral route for the reduction of postoperative bleeding in total primary hip arthroplasty: a prospective, randomized, double-blind, controlled study. Blood Coagulation and Fibrinolysis 2021;32(2):132-9. - PubMed
    1. NCT04187014. Oral tranexamic acid vs. oral aminocaproic acid to reduce blood loss after total hip replacement. clinicaltrials.gov/ct2/show/NCT04187014 (first received 2 December 2019).
Murkin 1995 {published data only}
    1. Murkin JM, Shannon NA, Bourne RB, Rorabeck CH, Cruickshank M, Wyile G. Aprotinin decreases blood loss in patients undergoing revision or bilateral total hip arthroplasty. Anesthesia and Analgesia 1995;80(2):343-8. - PubMed
Murkin 2000 {published data only}
    1. Murkin JM, Haig GM, Beer KJ, Cicutti N, McCutchen J, Comunale ME, et al. Aprotinin decreases exposure to allogeneic blood during primary unilateral total hip replacement. Journal of Bone and Joint Surgery 2000;82(5):675-84. - PubMed
NCT02922582 {published data only}
    1. NCT02922582. Study of local administration of depo TXA for reduced postsurgical bleeding in subjects undergoing TKA. clinicaltrials.gov/ct2/show/NCT02922582 (first received 28 September 2016).
Niskanen 2005 {published data only}
    1. Niskanen RO, Korkala OL. Tranexamic acid reduces blood loss in cemented hip arthroplasty: a randomized, double-blind study of 39 patients with osteoarthritis. Acta Orthopaedica 2005;76(6):829-32. - PubMed
North 2016 {published data only}
    1. NCT01683955. Topical tranexamic acid and acute blood loss in total hip arthroplasty. clinicaltrials.gov/ct2/show/NCT01683955 (first received 8 September 2012).
    1. North WT, Mehran N, Davis JJ, Silverton CD, Weir RM, Laker MW. Topical vs intravenous tranexamic acid in primary total hip arthroplasty: a double-blind, randomized controlled trial. Journal of Arthroplasty 2016;31(5):1022-6. - PubMed
Orpen 2006 {published data only}
    1. Orpen NM, Little C, Walker G, Crawfurd EJ. Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. The Knee 2006;13(2):106-10. - PubMed
Painter 2018 {published data only}
    1. ACTRN12613000323729. Tranexamic acid in lower limb arthroplasty pilot trial. trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12613000323729 (first received 22 March 2013).
    1. Painter TW, Daly DJ, Kluger R, Rutherford A, Ditoro A, Grant C, et al. Intravenous tranexamic acid and lower limb arthroplasty-a randomised controlled feasibility study. Anaesthesia and Intensive Care 2018;46(4):386-95. - PubMed
Peng 2021 {published data only}
    1. ChiCTR-INR-16010270. Peri-articular tranexamic acid injection in total knee/hip arthroplasty: a prospective randomized controlled trial. trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-INR-16010270 2016.
    1. Peng HM, Wang W, Lin J, Weng XS, Qian WW, Wang WD. Multimodal peri-articular injection with tranexamic acid can reduce postoperative blood loss versus intravenous tranexamic acid in total knee arthroplasty: a randomized controlled trial. Journal of Orthopaedic Surgery 2021;16(1):546. - PMC - PubMed
Petsatodis 2006 {published data only}
    1. Petsatodis G, Samoladas E, Christodoulou A, Hatzokos I, Pournaras I. Does aprotinin reduce blood loss in total hip arthroplasty? Orthopedics 2006;29(1):75-7. - PubMed
Ray 2005 {published data only}
    1. Ray M, Hatcher S, Crawford S, Crawford R, McLoughlin L. Aprotinin and epsilon aminocaproic acid are equally effective in reducing blood loss after primary total hip arthroplasty - a prospective randomised double blind placebo controlled study. Combined Orthopaedic Associations 2005;Suppl III:302‐30a. - PubMed
    1. Ray M, Hatcher S, Whitehouse SL, Crawford S, Crawford R. Aprotinin and epsilon aminocaproic acid are effective in reducing blood loss after primary total hip arthroplasty--a prospective randomized double-blind placebo-controlled study. Journal of Thrombosis and Haemostasis 2005;3(7):1421-7. - PubMed
Schott 1995 {published data only}
    1. Schott U, Sollen C, Axelsson K, Rugarn P, Allvin I. Desmopressin acetate does not reduce blood loss during total hip replacement in patients receiving dextran. Acta Anaesthesiologica Scandinavica 1995;39(5):592-8. - PubMed
Sershon 2020 {published data only}
    1. Fillingham YA, Darrith B, Calkins TE, Abdel MP, Malkani AL, Schwarzkopf R, et al. 2019 Mark Coventry Award: A multicentre randomized clinical trial of tranexamic acid in revision total knee arthroplasty: does the dosing regimen matter? The Bone and Joint Journal 2019;101-B(7 Suppl C):10-6. - PubMed
    1. NCT02877381. Tranexamic acid in revision total joint arthroplasty. www.clinicaltrials.gov/ct2/show/NCT02877381 (first received 14 April 2016).
    1. Sershon RA, Fillingham YA, Abdel MP, Malkani AL, Schwarzkopf R, Padgett DE, et al. The optimal dosing regimen for tranexamic acid in revision total hip arthroplasty: a multicenter randomized clinical trial. Journal of Bone and Joint Surgery. American Volume 2020;102(21):1883-90. - PubMed
Staniforth 2017 {published data only}
    1. NCT02393963. Intra-articular tranexamic acid in the reduction of blood transfusions in primary total hip and total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02393963 (first received 3 March 2015).
    1. Staniforth C, Aragola S. Does low dose intra-articular TXA reduce blood loss after primary THA and TKA? A randomized placebo control trial. Canadian Journal of Anesthesia 2017;64(1 Suppl 1):S130-1.
Stowers 2017 {published data only}
    1. NCT02278263. Tranexamic acid in knee joint surgery. clinicaltrials.gov/ct2/show/NCT02278263 (first received 18 September 2014).
    1. Stowers MDJ, Aoina J, Vane A, Poutawera V, Hill AG, Munro JT. Tranexamic acid in knee surgery study-a multicentered, randomized, controlled trial. Journal of Arthroplasty 2017;32(11):3379-84. - PubMed
Tanaka 2001 {published data only}
    1. Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, Ishii S. Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee. Journal of Bone and Joint Surgery 2001;83(5):702-5. - PubMed
Tsukada 2019 {published data only}
    1. Tsukada S, Kurosaka K, Nishino M, Maeda T, Yonekawa Y, Hirasawa N. Intra-articular tranexamic acid as an adjunct to intravenous tranexamic acid for simultaneous bilateral total knee arthroplasty: a randomized double-blind, placebo-controlled trial. BMC Musculoskeletal Disorders 2019;20(1):464. - PMC - PubMed
    1. UMIN000026137. Intravenous versus combined intravenous and intra-articular tranexamic acid for simultaneous bilateral total knee arthroplasty: randomized controlled trial. center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030035 (first received 14 February 2017).
Tsukada 2020 {published data only}
    1. Tsukada S, Kurosaka K, Nishino M, Maeda T, Hirasawa N, Matsue Y. Intraoperative intravenous and intra-articular plus postoperative intravenous tranexamic acid in total knee arthroplasty: a placebo-controlled randomized controlled trial. Journal of Bone and Joint Surgery. American volume 2020;102(8):687-92. - PubMed
    1. UMIN000030237. Additional postoperative intravenous tranexamic acid administration versus placebo administration for patients treated with intraoperative combined intravenous and intra-articular tranexamic acid in total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034537 (first received 3 December 2017).
Utada 1997 {published data only}
    1. Utada K, Matayoshi Y, Sumi C, Itaya M, Miyawaki H, Ito M, et al. Aprotinin 2 million kiu reduces perioperative blood loss in patients undergoing primary total hip replacement. Masui 1997;46(1):77-82. - PubMed
Veien 2002 {published data only}
    1. Veien M, Sorensen JV, Madsen F, Juelsgaard P. Tranexamic acid given intraoperatively reduces blood loss after total knee replacement: a randomized, controlled study. Acta Anaesthesiologica Scandinavica 2002;46(10):1206-11. - PubMed
Veien 2005 {published data only}
    1. Veien M, Juelsgaard P. A dose-response study of tranexamic acid. The effect on nausea and blood loss after total knee replacement. Ugeskr Laeger 2005;167(14):1513-6. - PubMed
Vles 2020 {published data only}
    1. Ghijselings S, Jacobs B, Driesen R, Corten K. Topical vs intravenous administration of tranexamic acid in direct anterior hip arthroplasty-a prospective randomized trial. Hip International 2015;25(Suppl 1):S93.
    1. NCT01940692. Topical and intravenous administration of TXA are equally effective in DAA THA. clinicaltrials.gov/ct2/show/NCT01940692 (first received 28 August 2013).
    1. Vles GF, Corten K, Driesen R, Elst C, Ghijselings SG. Hidden blood loss in direct anterior total hip arthroplasty: a prospective, double blind, randomized controlled trial on topical versus intravenous tranexamic acid. Musculoskeletal Surgery 2020;10:1-7. - PubMed
Wang 2018 {published data only}
    1. ChiCTR-IPR-17012265. Blood-sparing efficacy of multiple doses of oral tranexamic acid administration in enhanced-recovery primary total knee arthroplasty: a randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=20936 2017.
    1. Wang D, Wang HY, Luo ZY, Meng WK, Pei FX, Li Q, et al. Blood-conserving efficacy of multiple doses of oral tranexamic acid associated with an enhanced-recovery programme in primary total knee arthroplasty: A randomized controlled trial. The Bone and Joint Journal 2018;100-B(8):1025-32. - PubMed
Wang 2019a {published data only}
    1. ChiCTR-IPR-17012264. The clinical effect of 15-day oral tranexamic acid in total knee arthroplasty with no tourniquet. trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-IPR-17012264 2017.
    1. Wang HY, Wang L, Luo ZY, Wang D, Tang X, Zhou ZK, et al. Intravenous and subsequent long-term oral tranexamic acid in enhanced-recovery primary total knee arthroplasty without the application of a tourniquet: a randomized placebo-controlled trial. BMC Musculoskeletal Disorders 2019;20(1):478. - PMC - PubMed
Wang 2019b {published data only}
    1. ChiCTR-IPR-17012266. Multiple doses of oral tranexamic acid administration reduce total blood loss in primary total hip arthroplasty:a randomized controlled trial. trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-IPR-17012266 2017.
    1. Wang D, Wang HY, Luo ZY, Pei FX, Zhou ZK, Zeng WN. Finding the optimal regimen for oral tranexamic acid administration in primary total hip arthroplasty: a randomized controlled trial. Journal of Bone and Joint Surgery. American Volume 2019;101(5):438-45. - PubMed
Wang 2019c {published data only}
    1. Wang D, Yang Y, He C, Luo ZY, Pei FX, Li Q, et al. Effect of multiple doses of oral tranexamic acid on haemostasis and inflammatory reaction in total hip arthroplasty: a randomized controlled trial. Thrombosis and Haemostasis 2019;119(1):92-103. - PubMed
Wu 2018 {published data only}
    1. ChiCTR1800015265. Blood loss and cost-effective?of oral vs intravenous tranexamic acid in primary total hip arthroplasty: a randomized clinical trial. www.chictr.org.cn/searchprojen.aspx 2018. - PubMed
    1. Wu Y, Zeng Y, Hu Q, Li M, Bao X, Zhong J, et al. Blood loss and cost-effectiveness of oral vs intravenous tranexamic acid in primary total hip arthroplasty: a randomized clinical trial. Thrombosis Research 2018;171:143-8. - PubMed
Xie 2016 {published data only}
    1. Xie J, Ma J, Yao H, Yue C, Pei F. Multiple boluses of intravenous tranexamic acid to reduce hidden blood loss after primary total knee arthroplasty without tourniquet: a randomized clinical trial. Journal of Arthroplasty 2016;31(11):2458-64. - PubMed
Xie 2017 {published data only}
    1. Xie J, Hu Q, Ma J, Huang Q, Pei F. Multiple boluses of intravenous tranexamic acid to reduce hidden blood loss and the inflammatory response following enhanced-recovery primary total hip arthroplasty: a randomised clinical trial. Bone and Joint Journal 2017;99-B(11):1442-9. - PubMed
Xu 2023 {published data only}
    1. ChiCTR1900026092. Effects of tranexamic acid combined with dexamethasone on perioperative inflammatory response and fibrinolytic system in total knee arthroplasty: a prospective randomized controlled study. www.chictr.org.cn/showprojen.aspx?proj=43583 2019.
    1. Xu H, Xie J, Yang J, Huang Z, Wang D, Pei F. Synergistic effect of a prolonged combination course of tranexamic acid and dexamethasone involving high initial doses in total knee arthroplasty: a randomized controlled trial. Journal of Knee Surgery 2023;36(5):515-23. - PubMed
Xue 2021 {published data only}
    1. ChiCTR2000039368. Efficacy and safety of postoperative intravenous tranexamic acid in total knee arthroplasty: a prospective randomized controlled study. www.chictr.org.cn/showprojen.aspx?proj=63119 2020. - PMC - PubMed
    1. Xue CX, Yao YF, Lv H, Cheng L, Jing JH. Efficacy and safety of postoperative intravenous tranexamic acid in total knee arthroplasty: a prospective randomized controlled study. Orthopaedic Surgery 2021;13(8):2227-35. - PMC - PubMed
Yamasaki 2004 {published data only}
    1. Yamasaki S, Masuhara K, Fuji T. Tranexamic acid reduces blood loss after cementless total hip arthroplasty-prospective randomized study in 40 cases. International Orthopaedics 2004;28(2):69-73. - PMC - PubMed
Yang 2020 {published data only}
    1. ChiCTR-INR-16010287. Application of intra-articular injection of tranexamic acid combined with limb flexion in primary total knee arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=17493 2016.
    1. Yang J-Q, Yang L, Tan J-S, Huo K-P, Zhao L, Cai D-Z. Reduction of blood loss by intra-articular injection of tranexamic acid combined with knee and hip flexion at 45° during primary total knee arthroplasty: a randomized controlled trial. Orthopaedic Surgery 2020;12(6):1835-42. - PMC - PubMed
Yasli 2019 {published data only}
    1. NCT02094066. The effect of tranexamic acid for total hip arthroplasty. clinicaltrials.gov/ct2/show/NCT02094066 (first received 19 March 2014).
    1. Yasli SO, Tosun Z, Halici M, Kayaalti SK. Effects of high-dose tranexamic acid in total hip replacement: a prospective, double-blind, randomized controlled study. Journal of Surgery and Medicine 2019;3(1):39-43.
Yen 2017 {published data only}
    1. NCT02453802. Comparison of topical and infusion tranexamic acid after total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02453802 (first received 4 May 2015).
    1. Wang JW, Chen B, Lin P-C, Yen S-H, Huang C-C, Kuo F-C. The efficacy of combined use of rivaroxaban and tranexamic acid on blood conservation in minimally invasive total knee arthroplasty a double-blind randomized, controlled trial. In: Journal of Arthroplasty. 2016. - PubMed
    1. Yen SH, Lin PC, Chen B, Huang CC, Wang JW. Topical tranexamic acid reduces blood loss in minimally invasive total knee arthroplasty receiving rivaroxaban. BioMed Research International 2017;2017:9105645. - PMC - PubMed
Yen 2021 {published data only}
    1. NCT02865174. Topical tranexamic acid and Floseal® in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02865174 (first received 9 August 2016).
    1. Yen SH, Lin PC, Wu CT, Wang JW. Comparison of effects of a thrombin-based hemostatic agent and topical tranexamic acid on blood loss in patients with preexisting thromboembolic risk undergoing a minimally invasive total knee arthroplasty. a prospective randomized controlled trial. BioMed Research International 2021;2021:2549521. - PMC - PubMed
Zeng 2017 {published data only}
    1. ChiCTR-TRC-14004474. Intravenous combined with topical administration of tranexamic acid in primary total hip arthroplasty: a randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=5096 2014. - PMC - PubMed
    1. Zeng Y, Si HB, Shen B, Yang J, Zhou ZK, Kang PD, et al. Intravenous combined with topical administration of tranexamic acid in primary total hip arthroplasty: a randomized controlled trial. Orthopaedic Surgery 2017;9(2):174-9. - PMC - PubMed
Zeng 2018 {published data only}
    1. Zeng Y, Si H, Li C, Wu Y, Shen B. Effect of knee flexion position and combined application of tranexamic acid on blood loss following primary total knee arthroplasty: a prospective randomized controlled trial. International Orthopaedics 2018;42(3):529-35. - PubMed
Zhang 2007 {published data only}
    1. Zhang F, Gao Z, Yu J. Clinical comparative studies on effect of tranexamic acid on blood loss associated with total knee arthroplasty. Chinese Journal of Reparative & Reconstructive Surgery 2007;21(12):1302-4. - PubMed
Zhao 2018 {published data only}
    1. Zhao H, Xiang M, Xia Y, Shi X, Pei FX, Kang P. Efficacy of oral tranexamic acid on blood loss in primary total hip arthroplasty using a direct anterior approach: a prospective randomized controlled trial. International Orthopaedics 2018;42(11):2535-42. - PubMed
Zohar 2004 {published data only}
    1. Ellis M, Zohar E, Ifrach N, Stern A, Sapir O, Fredman B. Oral tranexamic acid in total knee replacement: results of a randomized study. Vox Sanguinis 2004;87(Suppl 3):50.
    1. Zohar E, Ellis M, Ifrach N, Stern A, Sapir O, Fredman B. The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement. Anesthesia and Analgesia 2004;99(6):1679-83. - PubMed

References to studies excluded from this review

Abdel 2018 {published data only}
    1. Abdel MP, Chalmers BP, Taunton MJ, Pagnano MW, Trousdale RT, Sierra RJ. Intravenous versus topical tranexamic acid in total knee arthroplasty: both effective in a randomized clinical trial of 640 patients. Journal of Bone and Joint Surgery 2018;100(12):1023-9. - PubMed
Abrisham 2018 {published data only}
    1. Abrisham SMJ, Sobhan MR, Golkar-Khouzani E, Sonbolestan SA. The effect of topical tranexamic acid versus injection into the clamped drain on postsurgical bleeding in knee arthroplasty surgery: a double-blind randomized clinical trial study. Journal of Isfahan Medical School 2018;36(499):1206-12.
ACTRN12613001043729 {published data only}
    1. ACTRN12613001043729. Novel use of tranexamic acid in major joint surgery. trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12613001043729 (first received 16 September 2013).
ACTRN12616000606482 {published data only}
    1. ACTRN12616000606482. Tranexamic acid use in total hip replacement - beyond blood loss: a randomised clinical trial of efficacy of tranexamic acid in improving postoperative inpatient functional outcomes following anterior total hip replacement. trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12616000606482 2014.
ACTRN12616000907448 {published data only}
    1. ACTRN12616000907448. Tranexamic acid trial intravenous versus intra articular tranexamic acid in primary hip arthroplasty: a prospective randomised double blinded non inferiority trial. trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12616000907448 2016.
ACTRN12617000617369 {published data only}
    1. ACTRN12617000617369. Oral tranexamic acid to reduce blood loss in patients undergoing total knee replacements. trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12617000617369 2017.
Aguilera 2012 {published data only}
    1. Aguilera X, Videla S, Almenara M, Fernandez JA, Gich I, Celaya F. Effectiveness of tranexamic acid in revision total knee arthroplasty. Acta Orthopaedica Belgica 2012;78(1):68-74. - PubMed
Aguilera 2013 {published data only}
    1. Aguilera X, Martinez-Zapata MJ, Bosch A, Urrutia G, Gonzalez JC, Jordan M, et al. Efficacy and safety of fibrin glue and tranexamic acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial. Journal of Bone & Joint Surgery: American Volume 2013;95(22):2001-7. - PubMed
Aguilera 2015 {published data only}
    1. Aguilera X, Martinez-Zapata MJ, Hinarejos P, Jordan M, Leal J, Gonzalez JC, et al. Topical and intravenous tranexamic acid reduce blood loss compared to routine hemostasis in total knee arthroplasty: a multicenter, randomized, controlled trial. Archives of Orthopaedic and Trauma Surgery 2015;135(7):1017-25. - PubMed
Ahmed 2018 {published data only}
    1. Ahmed S, Ahmed A, Ahmad S, Atiq uz Zaman, Javed S, Aziz A. Blood loss after intraarticular and intravenous tranexamic acid in total knee arthroplasty. Journal of the Pakistan Medical Association 2018;68(10):1434-7. - PubMed
Akgul 2016 {published data only}
    1. Akgul T, Buget M, Salduz A, Edipoglu IS, Ekinci M, Kucukay S, et al. Efficacy of preoperative administration of single high dose intravenous tranexamic acid in reducing blood loss in total knee arthroplasty: a prospective clinical study. Acta Orthopaedica et Traumatologica Turcica 2016;50(4):429-31. - PMC - PubMed
Alshryda 2013 {published data only}
    1. Alshryda S, Mason J, Sarda P, Nargol A, Cooke N, Ahmad H, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total hip replacement: a randomized controlled trial (tranx-h). Journal of Bone and Joint Surgery 2013;95(21):1969-74. - PubMed
Alshryda 2013a {published data only}
    1. Alshryda S, Mason J, Vaghela M, Sarda P, Nargol A, Maheswaran S, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total knee replacement: a randomized controlled trial (tranx-k). Journal of Bone and Joint Surgery 2013;95(21):1961-8. - PubMed
Amar 2003 {published data only}
    1. Amar D, Grant FM, Zhang H, Boland PJ, Leung DH, Healey JA. Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery. Anesthesiology 2003;98(2):337-42. - PubMed
Bali 2011 {published data only}
    1. Bali K, Dhillon M, Prabhakar S. Tranexamic acid for control of blood loss in bilateral total knee replacement in a single stage. Indian Journal of Orthopaedics 2011;45(2):148-52. - PMC - PubMed
Benoni 1997 {published data only}
    1. Benoni G, Lethagen S, Fredin H. The effect of tranexamic acid on local and plasma fibrinolysis during total knee arthroplasty. Thrombosis Research 1997;85(3):195-206. - PubMed
Bloomfield 2012 {published data only}
    1. Bloomfield MR, Klika AK, Molloy RM, Froimson MI, Krebs VE, Barsoum WK. Prospective randomized evaluation of a collagen/thrombin and autologous platelet hemostatic agent during total knee arthroplasty. Journal of Arthroplasty 2012;27(5):695-702. - PubMed
Bouali 2011 {published data only}
    1. Bouali Y, Rais K, Belhaj H, Jabri H, Kaabachi O. Continuous versus repeated bolus of tranexamic acid for total knee arthroplasty. Transfusion and Haemostasis 2011;48:89.
Cao 2015 {published data only}
    1. Cao WJ, Zhu SL, Liu XD, Tang CJ, Zheng JW, Chen XY, et al. Tranexamic acid reduces blood loss in total knee arthroplasty: effectiveness and safety. Chinese Journal of Tissue Engineering Research 2015;19(31):4944-8.
Cao 2018a {published data only}
    1. Cao G, Huang Z, Xie J, Huang Q, Xu B, Zhang S, et al. The effect of oral versus intravenous tranexamic acid in reducing blood loss after primary total hip arthroplasty: a randomized clinical trial. Thrombosis Research 2018;164:48-53. - PubMed
Cao 2018b {published data only}
    1. Cao G, Xie J, Huang Z, Huang Q, Chen G, Lei Y, et al. Efficacy and safety of multiple boluses of oral versus intravenous tranexamic acid at reducing blood loss after primary total knee arthroplasty without a tourniquet: a prospective randomized clinical trial. Thrombosis Research 2018;171:68-73. - PubMed
Capdevila 1998 {published data only}
    1. Capdevila X, Calvet Y, Biboulet P, Biron C, Rubenovitch J, d'Athis F. Aprotinin decreases blood loss and homologous transfusions in patients undergoing major orthopedic surgery. Anesthesiology 1998;88(1):50-7. - PubMed
Chareancholvanich 2011a {published data only}
    1. Charoencholvanich K, Siriwattanasakul P. Tranexamic acid reduces blood loss and blood transfusion after TKA: a prospective randomized controlled trial. Clinical Orthopaedics and Related Research 2011;469(10):2874-80. - PMC - PubMed
Chen 2014 {published data only}
    1. Chen X, Xie S, Wang K. Effectiveness of tranexamic acid in total knee arthroplasty. Chinese Journal of Reparative and Reconstructive Surgery 2014;28(11):1338-41. - PubMed
Chen 2016c {published data only}
    1. Chen X, Cao X, Yang C, Guo K, Zhu Q, Zhu J. Effectiveness and safety of fixed-dose tranexamic acid in simultaneous bilateral total knee arthroplasty: a randomized double-blind controlled trial. Journal of Arthroplasty 2016;31(11):2471-5. - PubMed
ChiCTR1800015839 {published data only}
    1. ChiCTR1800015839. Efficacy of tranexamic acid combined with carbazochrome sodium sulfonate on blood loss in primary total knee arthroplasty: a prospective randomized controlled trial. www.chictr.org.cn/com/25/showprojen.aspx?proj=26960 2018.
ChiCTR1800016494 {published data only}
    1. ChiCTR1800016494. The antifibrinolytic and anti-inflammatory effect and safety of a loading high-dose intravenous tranexamic acid followed by multiple doses in peri-operative period of total hip/knee arthroplasty: a prospective, randomized, controlled trial. www.chictr.org.cn/showprojen.aspx?proj=28035 2018.
ChiCTR1800016640 {published data only}
    1. ChiCTR1800016640. The hemostasis, anticoagulation, antifibrinolytic and anti-inflammatory effect of the concomitant use of tranexamic acid and other drugs in peri-operative period of total hip/knee arthroplasty: a prospective, randomized, controlled trial. www.chictr.org.cn/showprojen.aspx?proj=28321 2018.
ChiCTR1800017563 {published data only}
    1. ChiCTR1800017563. Effectiveness and safety of batroxobin, tranexamic acid in reduction of blood loss in arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=24505 2018.
ChiCTR1800018049 {published data only}
    1. ChiCTR1800018049. Assessment of safety and efficacy of Xiaozhongzhitong mixture and tranexamic acid in perioperative knee replacement. www.chictr.org.cn/showprojen.aspx?proj=30187 2018.
ChiCTR‐INR‐16008801 {published data only}
    1. ChiCTR-INR-16008801. Tranexamic acid administration in primary total knee arthroplasty: intravenous combined with topical vs. intravenous vs. topical? www.chictr.org.cn/showprojen.aspx?proj=14814 2016.
ChiCTR‐INR‐16009770 {published data only}
    1. ChiCTR-INR-16009770. Intravenous application of tranexamic acid and intravenous and oral combination enhanced recovery after surgery to reduce postoperative hidden hemorrhage and inflammatory reaction-a prospective randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=16663 2016.
ChiCTR‐INR‐17010826 {published data only}
    1. ChiCTR-INR-17010826. The comparative study of topical administration of tranexamic acid plus cocktail analgesic and cocktail analgesic for reducing blood loss during total knee arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=18425 2017.
ChiCTR‐IOR‐14005705 {published data only}
    1. ChiCTR-IOR-14005705. Evaluation the efficiency and safety of intravenous tranexamic acid protocol for reducing the hidden blood loss in primary unilateral total knee arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=10114 2014.
ChiCTR‐IPR‐14005247 {published data only}
    1. ChiCTR-IPR-14005247. Comparison of different dose of intravenous tranexamic acid on blood loss following cementless total hip arthroplasty: a double-blind randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=9534 2014.
ChiCTR‐IPR‐15005884 {published data only}
    1. ChiCTR-IPR-15005884. Tranexamic acid used in joint replacement operation in perioperative period. www.chictr.org.cn/showprojen.aspx?proj=10332 2015.
ChiCTR‐IPR‐17011669 {published data only}
    1. ChiCTR-IPR-17011669. Effect of multiple doses of oral tranexamic acid on perioperative hemostasis and inflammatory reaction following total hip arthroplasty: a randomized placebo-controlled trial. www.chictr.org.cn/showprojen.aspx?proj=19897 2017.
ChiCTR‐IPR‐17011896 {published data only}
    1. ChiCTR-IPR-17011896. Investigation of the standardized dosing regimen of tranexamic acid in perioperative period of total joint arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=17038 2017.
ChiCTR‐TRC‐14004379 {published data only}
    1. ChiCTR-TRC-14004379. To investigate the effects of different procoagulant drugs in combination anticoagulant for arthroplasty perioperative bleeding and the risk of thrombosis. www.chictr.org.cn/showprojen.aspx?proj=5191 2014.
ChiCTR‐TRC‐14004440 {published data only}
    1. ChiCTR-TRC-14004440. Intra-articular vs intravenous tranexamic acid in total knee arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=5130 2014.
ChiCTR‐TRC‐14004671 {published data only}
    1. ChiCTR-TRC-14004671. Tranexamic acid administration in primary total hip arthroplasty: intravenous combined with topical vs intravenous? A randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=4902 2014.
Choufani 2015 {published data only}
    1. Choufani C, Barbier O, Bajard X, Ollat D, Versier G. Medical and economic impact of a haemostatic sealant on the rate of transfusion after total knee arthroplasty. Transfusion Clinique et Biologique 2015;22(1):22-9. - PubMed
Cornell 2017 {published data only}
    1. Cornell CN. What is the ideal route of administration of tranexamic acid in TKA? A randomized controlled trial. Clinical Orthopaedics and Related Research 2017;475(8):1997-8. - PMC - PubMed
CTRI/2010/091/001260 {published data only}
    1. CTRI/2010/091/001260. Efficacy of intra-articular tranexamic acid in pulmonary unilateral total klnee arthroplasty: a preliminary study. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=2057&EncHid=&us... 2010.
CTRI/2015/09/006185 {published data only}
    1. CTRI/2015/09/006185. Prospective randomizeddouble-blinded placebo controlled trial studying efficacy in terms of blood loss abd safety in terms DVT if intra-articualr tranexamic acid in unilateral total knee arthroplasty. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=5904&EncHid=&us... 2015.
CTRI/2017/04/008401 {published data only}
    1. CTRI/2017/04/008401. Comparison of local versus systemic tranexamic acid in total knee replacement. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=18304&EncHid=&u... 2017.
CTRI/2017/07/009076 {published data only}
    1. CTRI/2017/07/009076. Comparison of local versus systemic tranexamic acid in total knee replacement. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19351&EncHid=&u... 2017.
CTRI/2018/03/012728 {published data only}
    1. CTRI/2018/03/012728. To compare two doses of tranexamic acid in reducing bleeding and transfusions in total knee arthroplasty. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=17603&EncHid=&u... 2018.
Cvachovec 2011 {published data only}
    1. Cvachovec K, Sechovska H, Berousek J, Popelka S, Hladikova M. Aprotinin (antilysin spofa)--its effect on decreasing hemorrhage in the postoperative period in hip arthroplasty. Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca 2001;68(5):311-4. - PubMed
DeNapoli 2016 {published data only}
    1. De Napoli G, Ottolenghi J, Melo LM. Comparison of bleeding and transfusions in primary hip and knee arthroplasties with single doses of tranexamic acid vs. placebo in a University Hospital. A prospective study. Revista Colombiana de Ortopedia y Traumatología 2016;30(3):101-6.
DeSandesKimura 2016 {published data only}
    1. De Sandes Kimura O, Freitas E, Linhares Garcia PB, Leal DDC, Cury Fernandes MB. Tranexamic acid in high risk transfusion group: a comparative study. HIP International 2016;26(Suppl 2):S42.
Dong 2017 {published data only}
    1. Dong YL, Qian YN, Zhong XQ, Shen GJ, Cai CY. Effects of tranexamic acid combined with temporary drain clamping on postoperative blood loss in total knee arthroplasty. China Journal of Orthopaedics and Traumatology 2017;30(4):329-33. - PubMed
DRKS00007564 {published data only}
    1. DRKS00007564. Randomized controlled trial to determine the efficacy of EVICEL® on blood loss in orthopaedic surgery after total knee replacement (TKR). www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DR... 2014.
Drosos 2016 {published data only}
    1. Drosos GI, Ververidis A, Valkanis C, Tripsianis G, Stavroulakis E, Vogiatzaki T, et al. A randomized comparative study of topical versus intravenous tranexamic acid administration in enhanced recovery after surgery (eras) total knee replacement. Journal of Orthopaedics 2016;13(3):127-31. - PMC - PubMed
EUCTR‐2009‐012043‐42‐UK {published data only}
    1. 2009-012043-42. The effect of a human surgical sealant on range of motion in total knee replacement. www.clinicaltrialsregister.eu/ctr-search/trial/2009-012043-42/GB 2011.
EUCTR‐2015‐000107‐94 {published data only}
    1. 2015-000107-94. Blood-sparing during hip prosthesis surgery with Exacyl® in patients treated with rivaroxaban (ESPER). www.clinicaltrialsregister.eu/ctr-search/search?query=2015-000107-94 2015.
Fernandez‐Collins 2017 {published data only}
    1. Fernandez-Cortinas AB, Quintans-Vazquez JM, Gomez-Suarez F, Murillo OS, Sanchez-Lopez BR, Pena-Gracia JM. Effect of tranexamic acid administration on bleeding in primary total hip arthroplasty [Efecto de dosis unica intravenosa de acido tranexamico sobre el sangrado en artroplastia total de cadera. Estudio prospectivo, controlado y aleatorizado]. Revista Española de Cirugía Ortopédica y Traumatología 2017;61(5):289-95. - PubMed
Fraval 2017 {published data only}
    1. Fraval A, Effeney P, Fiddelaers L, Smith B, Towell B, Tran P. Obtain A: Outcome benefits of tranexamic acid in hip arthroplasty. A randomized double-blinded controlled trial. Journal of Arthroplasty 2017;32(5):1516-9. - PubMed
Fraval 2019 {published data only}
    1. Fraval A, Duncan S, Murray T, Duggan J, Tirosh O, Tran P. Obtain E: Outcome benefits of tranexamic acid in hip arthroplasty with enoxaparin: a randomised double-blinded controlled trial. HIP International 2019;29(3):239-44. - PubMed
Freick 1983 {published data only}
    1. Freick H, Reuter HD, Piontek R. Supplementary preoperative prevention of thromboembolism through the use of aprotinin in alloplastic hip joint prosthesis? Die Medizinische Welt 1983;34(21):614-9. - PubMed
George 2018 {published data only}
    1. George J, Eachempati KK, Subramanyam KN, Gurava Reddy AV. The comparative efficacy and safety of topical and intravenous tranexamic acid for reducing perioperative blood loss in total knee arthroplasty- a randomized controlled non-inferiority trial. The Knee 2018;25(1):185-91. - PubMed
Gonzalez‐Osuna 2017 {published data only}
    1. 2015-003408-21. A phase II/III, randomized, controlled, single blind study to evaluate the haemostatic efficacy and safety of topically applied TT-173 in patients undergoing knee arthroplasty. www.clinicaltrialsregister.eu/ctr-search/trial/2015-003408-21/ES 2015.
    1. Gonzalez-Osuna A, Videla S, Canovas E, Urrutia G, Rojas S, Lopez R, et al. Hestat: Study protocol for a phase II/III, randomized, placebo-controlled, single blind study to evaluate the new hemostatic agent tt-173 in total knee arthroplasty. Contemporary Clinical Trials 2017;61:16-22. - PubMed
Guerreiro 2017 {published data only}
    1. Guerreiro JPF, Badaro BS, Balbino JRM, Danieli MV, Queiroz AO, Cataneo DC. Application of tranexamic acid in total knee arthroplasty - prospective randomized trial. Open Orthopaedics Journal 2017;11:1049-57. - PMC - PubMed
Haas 1984 {published data only}
    1. Haas S, Ketterl R, Stemberger A, Wendt P, Fritsche HM, Kienzle H, et al. The effect of aprotinin on platelet function, blood coagulation and blood lactate level in total hip replacement - a double blind clinical trial. Advances in Experimental Medicine and Biology 1984;167:287-97. - PubMed
    1. Haas S, Ketterl R, Stemberger A, Wendt P, Fritsche HM, Kienzle H, et al. The effect of aprotinin on platelet function, blood coagulation and blood lactate level in total hip replacement - a double blind clinical trial. Thrombosis and Haemostasis 1983;50(1):456. - PubMed
Hegde 2013 {published data only}
    1. Hegde C, Wasnik S, Kulkarni S, Pradhan S, Shetty V. Simultaneous bilateral computer assisted total knee arthroplasty: the effect of intravenous or intraarticular tranexamic acid. Journal of Arthroplasty 2013;28(10):1888-91. - PubMed
Heyse 2014 {published data only}
    1. Heyse TJ, Haas SB, Drinkwater D, Lyman S, Kim HJ, Kahn BA, et al. Intraarticular fibrinogen does not reduce blood loss in TKA: a randomized clinical trial knee. Clinical Orthopaedics and Related Research 2014;472(1):272-6. - PMC - PubMed
    1. NCT01235715. The use of Evicel to reduce blood loss in total knee replacement surgery. clinicaltrials.gov/ct2/show/NCT01235715 2010.
Hill 2018 {published data only}
    1. Hill J, Magill P, Dorman A, Hogg R, Eggleton A, Benson G et al. Assessment of the effect of addition of 24 hours of oral tranexamic acid post-operatively to a single intraoperative intravenous dose of tranexamic acid on calculated blood loss following primary hip and knee arthroplasty (trac-24): a study protocol for a randomised controlled trial. Trials 2018;19(1):413. [DOI: 10.1186/s13063-018-2784-3] - DOI - PMC - PubMed
Hou 2017 {published data only}
    1. Hou ZY, Sun Y L, Pang T, Lv D, Zhu B, Li Z et al. Effects of two different tranexamic acid administration methods on perioperative blood loss in total hip arthroplasty: study protocol for a prospective, open-label, randomized, controlled clinical trial [Chinese]. Zhonghua Yi Xue Za Zhi 2017;21(15):2314-9.
Hourlier 2014 {published data only}
    1. Hourlier H, Fennema P. Single tranexamic acid dose to reduce perioperative morbidity in primary total hip replacement: a randomised clinical trial. Hip International 2014;24(1):63-8. - PMC - PubMed
Hourlier 2015 {published data only}
    1. Hourlier H, Reina N, Fennema P. Single dose intravenous tranexamic acid as effective as continuous infusion in primary total knee arthroplasty: a randomised clinical trial. Archives of Orthopaedic and Trauma Surgery 2015;135:465-71. - PubMed
IRCT201009204780N1 Iranian Registry {published data only}
    1. IRCT201009204780N1. Effectiveness of oral tranexamic acid administration on blood loss after knee artroplasty. en.irct.ir/trial/5109. - PubMed
IRCT201012264784N2 Iranian Registry {published data only}
    1. IRCT201012264784N2. Effect of prophylactic administration of fibrinogen concentrate on volume of transfused packed RBC during and after totla hip arthroplasty in sina hospital during 2011-2012. en.irct.ir/trial/5126 2012.
IRCT201509056280N8 Iranian Registry {published data only}
    1. IRCT201509056280N8. The comparison of intravenous tranexamic acid and topical tranexamic acid efficacy on postoperative bleeding after total hip arthroplasty surgery. en.irct.ir/trial/6725 2015.
IRCT2016122730123N1 Iranian Registry {published data only}
    1. IRCT2016122730123N1. The effectiveness of topical tranexamic acid compare to injection into the clamp drain on the bleeding after knee arthroplasty surgery. en.irct.ir/trial/24034 2016.
IRCT20180411039272N1 Iranian Registry {published data only}
    1. IRCT20180411039272N1. Comparison of the efficacy of oral, intravenous and topical tranexamic acid in reducing bleeding after total knee arthroplasty. en.irct.ir/trial/30541 2018.
Iseki 2018 {published data only}
    1. Iseki T, Tsukada S, Wakui M, Yoshiya S. Intravenous tranexamic acid only versus combined intravenous and intra-articular tranexamic acid for perioperative blood loss in patients undergoing total knee arthroplasty. European Journal of Orthopaedic Surgery & Traumatology 2018;28:1397-402. - PubMed
Ishida 2011 {published data only}
    1. Ishida K, Tsumura N, Kitagawa A, Hamamura S, Fukuda K, Dogaki Y, et al. Intra-articular injection of tranexamic acid reduces not only blood loss but also knee joint swelling after total knee arthroplasty. International Orthopaedics 2011;35(11):1639-45. - PMC - PubMed
ISRCTN43363116 {published data only}
    1. ISRCTN43363116. Effects of tranexamic acid in total knee arthroplasty - pilot study. www.isrctn.com/ISRCTN43363116 2005.
ISRCTN58790500 {published data only}
    1. ISRCTN58790500. Investigating the influence of intravenous and oral tranexamic acid on blood loss for patients undergoing primary hip and knee replacements. www.isrctn.com/ISRCTN58790500 2016.
ISRCTN59245192 {published data only}
    1. ISRCTN59245192. Topical tranexamic acid in total hip replacement. www.isrctn.com/ISRCTN59245192 2012.
ISRCTN68578366 {published data only}
    1. ISRCTN68578366. Topical tranexamic acid in total knee replacement. doi.org/10.1186/ISRCTN68578366 2012.
Janatmakan 2021 {published data only}
    1. Janatmakan F, Javaherforooshzadeh F, Khorrami M, Jarirahmadi S, Khademali H. Is intra-articular administration of fibrinogen effective in postoperative total knee arthroplasty blood loss? A randomized clinical trial. Anesthesiology and Pain Medicine 2021;11(1):e107431. - PMC - PubMed
Joyce 2015 {published data only}
    1. Joyce DM, Klika AK, Mutnal A, Krebs V, Molloy R, Knothe U et al. Prospective randomised evaluation of a collagen/thrombin and autologous platelet haemostatic agent during cementless total hip arthroplasty. Blood Transfusion 2015;13(3):456-63. - PMC - PubMed
Karampinas 2019 {published data only}
    1. Karampinas PK, Megaloikonomos PD, Lampropoulou-Adamidou K, Papadelis EG, Mavrogenis AF, Vlamis JA et al. Similar thromboprophylaxis with rivaroxaban and low molecular weight heparin but fewer hemorrhagic complications with combined intra-articular and intravenous tranexamic acid in total knee arthroplasty. European Journal of Orthopaedic Surgery & Traumatologie 2019;29(2):455-60. - PubMed
KCT0003084 {published data only}
    1. KCT0003084. The effect of biodegradable bone hemostatic on the bleeding and functional restoration in total knee arthroplasty patients. trialsearch.who.int/Trial2.aspx?TrialID=KCT0003084 2018.
Ketterl 1982 {published data only}
    1. Ketterl R, Haas S, Wendt P, Stemberger A, Fritsche HM. The influence of aprotinin on the blood lactate level, the platelet function and on parameters of coagulation following total hip replacement [Einflufl von Aprotinin auf den Blut-Lactatspiegel und auf Gerinnungsparameter beim alloarthroplastischen Hiiftgelenkersatz: Eine Doppelblindstudie]. Langenbecks Archiv fur Chirurgie 1982;12(Suppl 2):68.
Kim 2012 {published data only}
    1. Kim HJ, Fraser MR, Kahn B, Lyman, S, Figgie MP. The efficacy of a thrombin-based hemostatic agent in unilateral total knee arthroplasty: a randomized controlled trial. Journal of Bone and Joint Surgery 2012;94(13):1160-5. - PubMed
Kim 2018 {published data only}
    1. Kim YH, Pandey K, Park JW, Kim J. Comparative efficacy of intravenous with intra-articular versus intravenous only administration of tranexamic acid to reduce blood loss in knee arthroplasty. Orthopedics 2018;41(6):e827-30. - PubMed
Kim  2020 {published data only}
    1. Kim JK, Park JY, Lee DY, Ro DH, Han HS, Lee MC. Optimal dose of topical tranexamic acid considering efficacy and safety in total knee arthroplasty: a randomized controlled study. Knee Surgery, Sports Traumatology, Arthroscopy 2020;31(1):3409-17. - PubMed
Kim 2021 {published data only}
    1. Kim JK, Ro DH, Han SM, Lee MC, Han HS. Efficacy and safety of bioabsorbable bone hemostatic agent in total knee arthroplasty: a prospective randomized controlled trial. Clinical and Applied Thrombosis and Hemostasis 2021;27:1-6. - PMC - PubMed
Kim 2021a {published data only}
    1. Kim KI, Bae JK, Kim JH, Gwak HG, Lee SH. Tranexamic acid in a periarticular multimodal cocktail injection for blood management in total knee arthroplasty: a prospective randomized study. BMC Musculoskeletal Disorders 2021;22:675. - PMC - PubMed
Kluba 2012 {published data only}
    1. Kluba T, Fiedler K, Kunze B, Ipach I, Suckel A. Fibrin sealants in orthopaedic surgery: practical experiences derived from use of quixil in total knee arthroplasty. Knee Arthroplasty 2012;132(8):1147-52. - PubMed
Kraft 1999 {published data only}
    1. Kraft V, Opel R, Reineke H, Trepte CT. Aprotinin as a foreign blood saving measure in knee end prosthetic operations. Osteosynthese International 1999;7(Suppl 2):174-6.
Kumar 2018 {published data only}
    1. Kumar A. Outcomes of intraoperative hemostasis in total hip arthroplasty using IV tranexamic acid, topical feracrylum and epinephrine. In: Orthopaedic World Congress. 2018.
Kyriakopoulos 2019 {published data only}
    1. Kyriakopoulos G, Oikonomou L, Panagopoulos A, Kotsarinis G, Vlachou M, Anastopoulos G et al. Transfusion rate, hospital stay and cost-effectiveness of intravenous or local administration of tranexamic acid in total hip and knee arthroplasty: A single-center randomized controlled clinical study. Orthopedic Reviews 2019;11(2):70-4. - PMC - PubMed
Lanoiselee 2018 {published data only}
    1. Lanoiselee J, Zufferey PJ, Ollier E, Hodin S, Delavenne X. Is tranexamic acid exposure related to blood loss in hip arthroplasty? A pharmacokinetic-pharmacodynamic study. British Journal of Clinical Pharmacology 2018;84(2):310-9. - PMC - PubMed
Laoruengthana 2019 {published data only}
    1. Laoruengthana A, Rattanaprichavej P, Chaibhuddanugul N, Varakornpipat P, Galassi M, Pongpirul K. Blood loss reduction: effect of different knee prosthesis designs and use of tranexamic acid-a randomized controlled trial. European Journal of Orthopaedic Surgery & Traumatologie 2019;29(8):1519-24. - PubMed
Laoruengthana 2019a {published data only}
    1. Laoruengthana A, Rattanaprichavej P, Rasamimongkol S, Galassi M, Weerakul S, Pongpirul K. Intra-articular tranexamic acid mitigates blood loss and morphine use after total knee arthroplasty. A randomized controlled trial. Journal of Arthroplasty 2019;34(5):877-81. - PubMed
Lassen 2006 {published data only}
    1. Lassen MR, Solgaard S, Kjersgaard AG, Olsen C, Lind B, Mittet K et al. A pilot study of the effects of vivostat patient-derived fibrin sealant in reducing blood loss in primary hip arthroplasty. 2006 12;3:352-7. - PubMed
Lee 2017b {published data only}
    1. Lee QJ, Chang WY, Wong YC. Blood-sparing efficacy of oral tranexamic acid in primary total hip arthroplasty. Journal of Arthroplasty 2017;32(1):139-42. - PubMed
Leino 2010 {published data only}
    1. Leinojmn KA, Palve HK, Tiusanen HT, Tuppurainen TT. The effect of desmopressin on blood loss in patients with rheumatoid arthritis undergoing hip arthroplasty. Acta Anaesthesiology Scandinavia 2010;54(7):863-70. - PubMed
Li 2020 {published data only}
    1. Li MM, Kwok JY, Chung KY, Cheung KW, Chiu KH, Chau WW, et al. Prospective randomized trial comparing efficacy and safety of intravenous and intra-articular tranexamic acid in total knee arthroplasty. Knee Surgery and Related Research 2020;32(1):62. - PMC - PubMed
Lin 2011 {published data only}
    1. Lin PC, Hsu CH, Chen WS, Wang JW. Does tranexamic acid save blood in minimally invasive total knee arthroplasty? Clinical Orthopedic Related Research 2011;469(7):1995-2002. - PMC - PubMed
Lin 2012 {published data only}
    1. Lin PC, Hsu CH, Huang CC, Chen WS, Wang JW. The blood-saving effect of tranexamic acid in minimally invasive total knee replacement: is an additional pre-operative injection effective? Journal of Bone and Joint Surgery 2012;94(7):932-6. - PubMed
Lo 2020 {published data only}
    1. Lo STAk J, Gallo J, Bal Az L, Zapletalo, AJ. Optimal route for tranexamic acid in diabetics and obese patients undergoing primary total knee arthroplasty - a data from randomized study. Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca 2020;87(6):429-37. - PubMed
Lostak 2020 {published data only}
    1. Lostak J, Gallo J, Balaz L, Zapletalova J. Combined and intravenous administration of TXA reduces blood loss more than topical adinistration in primary total knee arthroplasty: a randomized clinical trial. Biomedical Papers of the Medical Faculty of Palacky University in Olomouc, Czech Republic 2020;164:1-9. - PubMed
Lostak 2020a {published data only}
    1. Lostak J, Gallo J, Slavik L, Zapletalova J, Balaz L. Monitoring of fibrinolytic system activity with plasminogen, D-dimers and FDP in primary total knee arthroplasty (TKA) after topical, intravenous or combined administration of tranexamic acid. Biomedical Papers of the Medical Faculty of Palacky University in Olomouc, Czech Republic 2020;164(2):168-76. - PubMed
Lum 2018 {published data only}
    1. Lum ZC, Manoukian MAC, Pacheco CS, Nedopil AJ, Giordani M, Meehan JP. Intravenous tranexamic acid versus topical aminocaproic acid: which method has the least blood loss and transfusion rates? Journal of the American Academy of Orthopedic Surgeons 2018;2(11):e072. - PMC - PubMed
Luo 2012 {published data only}
    1. Luo DF, Chen YP, Gao H, Chen L, Li SZ. Application of microporous polysaccharide hemospheres in total hip arthroplasty. Chinese Journal of Tissue Engineering Research 2012;16(26):4792-5.
Luo 2018a {published data only}
    1. Luo ZY, Wang HY, Wang D, Zhou K, Pei FX, Zhou ZK. Oral vs intravenous vs topical tranexamic acid in primary hip arthroplasty: a prospective, randomized, double-blind, controlled study. Journal of Arthroplasty 2018;33(3):786-93. - PubMed
Magill 2021 {published data only}
    1. Magill P, Hill JC, Bryce L, Martin U, Dorman A, Hogg R et al. Oral tranexamic acid for an additional 24 hours postoperatively versus a single preoperative intravenous dose for reducing blood loss in total hip arthroplasty: results of a randomized controlled trial (TRAC-24). The Bone and Joint Journal 2021;103-B(7):1197-205. - PubMed
Maniar 2017 {published data only}
    1. Maniar RN, Singhi T, Patil A, Kumar G, Maniar P, Singh J. Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty - a prospective randomized controlled study. The Knee 2017;24(1):100-6. - PubMed
Martin 2014 {published data only}
    1. Martin JG, Cassatt KB, Kincaid-Cinnamon KA, Westendorf DS, Garton AS, Lemke JH. Topical administration of tranexamic acid in primary total hip and total knee arthroplasty. Journal of Arthroplasty 2014;29(5):889-94. - PubMed
McConnell 2011 {published data only}
    1. McConnell JS, Shewale S, Munro NA, Shah K, Deakin AH, Kinninmonth AW. Reduction of blood loss in primary hip arthroplasty with tranexamic acid or fibrin spray. Acta Orthopaedica 2011;82(6):660-3. - PMC - PubMed
McConnell 2012 {published data only}
    1. McConnell JS, Shewale S, Munro NA, Shah K, Deakin AH, Kinninmonth AW. Reducing blood loss in primary knee arthroplasty: a prospective randomised controlled trial of tranexamic acid and fibrin spray. The Knee 2012;19(4):295-8. - PubMed
Mehta 2019a {published data only}
    1. Mehta N, Goel N, Goyal A, Joshi D, Chaudhary D. A prospective comparative study between intravenous and intraarticular tranexamic acid administration in decreasing the perioperative blood loss in total knee arthroplasty. Journal of Arthroscopy and Joint Surgery 2019;6(1):70-3.
Melo 2017 {published data only}
    1. Melo GLR, Lages DS, Madureira Junior JL, Pellucci GP, Pellucci JWJ. The use of tranexamic acid in patients submitted to primary total hip arthroplasty: an evaluation of its impact in different administration protocols. Revista Brasileria Ortopedia 2017;52(Suppl 1):34-9. - PMC - PubMed
Mena 2002 {published data only}
    1. Mean M, Cabrera MC, Labbe M, Bermuidez E, Lehuede M, Santelices E. Tranexamic acid in knee replacement [Acido Tranexamico en Recambio de Rodilla]. Revisita Chilena Anestesia 2002;31(12):176.
Mercuriali 2004 {published data only}
    1. Mercuriali F, Inghilleri G, Aloni A, Santoleri L, Angeloro D, Capitani D et al. Autologous fibrin glue (AFG) reduces blood loss in patients submitted to total hip replacement (THR). Vox Sanguinis 2004;87(Suppl 3):35.
Meshram 2020 {published data only}
    1. Meshram P, Palanisamy JV, Seo JY, Lee JG, Kim TK. Combined intravenous and intraarticular tranexamic acid does not offer additional benefit compared with intraarticular use alone in bilateral TKA: a randomized controlled trial. Clinical Orthopaedics and Related Research 2020;478(1):45-54. - PMC - PubMed
Morales‐Avalos 2021a {published data only}
    1. Morales-Avalos R, Ramos-Morales TM, Espinoza-Galindo AM, Garay-Mendoza D, Pena-Martinez VM, Marfil-Rivera LJ et al. First comparative study of the effectiveness of the use of tranexamic acid against epsilon-aminocaproic acid via the oral route for the reduction of postoperative bleeding in TKA: a clinical trial. Journal of Knee Surgery 2021;34(4):383-405. - PubMed
Morales Santias 2020 {published data only}
    1. Morales Santias M, Mas Martinez J, Sanz-Reig J, Martinez Gimenez E, Verdu Roman C, Bustamante Suarez de Puga D. Topical tranexamic acid in cemented primary total knee arthroplasty without tourniquet: a prospective randomized study. European Journal of Orthopaedic Surgery & Traumatologie 2020;30(6):1003-8. - PubMed
Mortazavi 2020 {published data only}
    1. Mortazavi SJ, Sattartabar B, Moharrami A, Kalantar SH. Intra-articular versus intravenous tranexamic acid in total knee arthroplasty: a randomized clinical trial. Archives of Bone and Joint Surgery 2020;8(3):355-62. - PMC - PubMed
Motififard 2015 {published data only}
    1. Motififard M, Tahririan MA, Saneie M, Badiei S, Nemati A. Low dose perioperative intravenous tranexamic acid in patients undergoing total knee arthroplasty: a double-blind randomized placebo controlled clinical trial. Journal of Blood Transfusion 2015;1:1-5. - PMC - PubMed
Munoz Gomez 2013 {published data only}
    1. Munoz Gomez M, Paramo Fernandez JA. Intravenous administration of tranexamic acid to decrease bleeding and transfusion in knee and hip prosthetic surgery: is it safe and cost-effective? Medicina Clinica 2013;141(5):207-9. - PubMed
Najafi 2014 {published data only}
    1. Najafi A, Shariat Moharari R, Orandi AA, Etezadi F, SanatkarM Khajavi MR, et al. Prophylactic administration of fibrinogen concentrate in perioperative period of total hip arthroplasty: a randomized clinical trial study. Acta Medica Iranica 2014;52(11):804-10. - PubMed
NCT00161902 {published data only}
    1. NCT00161902. Efficacy and safety of fibrin sealant vapor heated solvent/detergent treated (FS VH S/D) for hemostasis in subjects undergoing total hip replacement. clinicaltrials.gov/ct2/show/NCT00161902.
NCT00167895 {published data only}
    1. NCT00167895. The use of platelet derived growth factors in total knee arthroplasty, a randomized trial. clinicaltrials.gov/ct2/show/NCT00167895.
NCT00375440 {published data only}
    1. NCT00375440. Tranexamic acid study. clinicaltrials.gov/ct2/show/NCT00375440.
NCT00378872 {published data only}
    1. NCT00378872. Tranexamic acid vs. Quixil - reducing blood loss in joint replacement. clinicaltrials.gov/ct2/show/NCT00378872 2006.
NCT00440921 {published data only}
    1. NCT00440921. Clinical trial for fibrin sealant in knee surgery. clinicaltrials.gov/ct2/show/NCT00440921.
NCT00668031 {published data only}
    1. NCT00668031. Effect of aprotinin on transfusion requirements and blood loss in patients undergoing elective primary total hip replacement. clinicaltrials.gov/ct2/show/NCT00668031.
NCT00985920 {published data only}
    1. NCT00985920. Topical tranexamic acid for total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT00985920.
NCT00990288 {published data only}
    1. NCT00990288. The use of Floseal to reduce bleeding in total knee replacement surgery. clinicaltrials.gov/ct2/show/NCT00990288.
NCT01027286 {published data only}
    1. NCT01027286. Prospective evaluation of vitagel for reduction in blood loss and pain following unilateral total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT01027286.
NCT01285024 {published data only}
    1. NCT01285024. A prospective study to evaluate the effectiveness of a haemostatic agent in primary unilateral total hip arthroplasty. clinicaltrials.gov/ct2/show/NCT01285024.
NCT01410240 {published data only}
    1. NCT01410240. Efficacy and safety of FLOSEAL for hemostasis in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT01410240.
NCT01449552 {published data only}
    1. NCT01449552. Temporary clamping of drains combined with tranexamic acid reduce blood loss after TKA: a prospective RCT. clinicaltrials.gov/ct2/show/NCT01449552.
NCT01472913 {published data only}
    1. NCT01472913. Fibrin sealant in bilateral simultaneous total knee arthroplasty with focus on blood loss, pain, swelling and strength. clinicaltrials.gov/ct2/show/NCT01472913.
NCT01656759 {published data only}
    1. NCT01656759. Use of a novel fibrin sealant in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT01656759.
NCT01816282 {published data only}
    1. NCT01816282. The use of fibrin sealant to reduce bleeding after total knee replacement. clinicaltrials.gov/ct2/show/NCT01816282.
NCT01850394 {published data only}
    1. NCT01850394. Efficacy of low-dose intra-articular tranexamic acid in total knee replacement. clinicaltrials.gov/ct2/show/NCT01850394.
NCT01866943 {published data only}
    1. NCT01866943. Role of topical tranexamic acid in total hip arthroplasty (TXA). clinicaltrials.gov/ct2/show/NCT01866943.
NCT01881568 {published data only}
    1. NCT01881568. Efficacy comparison of topical and intravenous tranexamic acid to reduce the number of blood transfusions in TKA (TRANEX1). clinicaltrials.gov/ct2/show/NCT01881568.
NCT01891461 {published data only}
    1. NCT01891461. Study to compare the addition of Floseal to our standard of care to control post operative bleeding in TKR. clinicaltrials.gov/ct2/show/NCT01891461.
NCT01937559 {published data only}
    1. NCT01937559. Topical tranexamic acid (TXA) in joint arthroplasty. clinicaltrials.gov/ct2/show/NCT01937559.
NCT01940523 {published data only}
    1. NCT01940523. Randomized controlled trial of tranexamic acid in total knee arthroplasty: intravenous vs. topical. clinicaltrials.gov/ct2/show/NCT01940523.
NCT02152917 {published data only}
    1. NCT02152917. Comparison of Floseal® and tranexamic acid on bleeding control after total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02152917.
NCT02252497 {published data only}
    1. NCT02252497. Tranexamic acid in total hip arthroplasty. (PORTO). clinicaltrials.gov/ct2/show/NCT02252497.
NCT02312440 {published data only}
    1. NCT02312440. Comparison of topical and intravenous tranexamic acid in total hip arthroplasty. clinicaltrials.gov/ct2/show/NCT02312440.
NCT02323373 {published data only}
    1. NCT02323373. Topical versus intravenous tranexamic acid in total knee arthroplasty (TRANEXTKA). clinicaltrials.gov/ct2/show/NCT02323373.
NCT02327117 {published data only}
    1. NCT02327117. Low dose peri- operative intra venous teranexamic acid reduces blood loss after total knee arthroplasty: a double blind randomized placebo controlled clinical trial. clinicaltrials.gov/ct2/show/NCT02327117.
NCT02374398 {published data only}
    1. NCT02374398. Clinical trial comparing tranexamic acid (TXA) with aquamantys sealer in total knee arthroplasty (TKA). clinicaltrials.gov/ct2/show/NCT02374398.
NCT02393300 {published data only}
    1. NCT02393300. Comparison of topical versus intravenous tranexamic acid in TKA. clinicaltrials.gov/ct2/show/NCT02393300.
NCT02427412 {published data only}
    1. NCT02427412. Evaluation of intraarticular tranexamic acid to reduction of total blood loss following knee-arthroplasty. clinicaltrials.gov/ct2/show/NCT02427412.
NCT02458729 {published data only}
    1. NCT02458729. The blood saving effect of tranexamic acid in total knee arthroplasty with rivaroxaban as thromboprophylaxis. clinicaltrials.gov/ct2/show/NCT02458729.
NCT02504125 {published data only}
    1. NCT02504125. The efficacy and safety of using tranexamic acid to reduce blood loss in simultaneous bilateral total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02504125.
NCT02553122 {published data only}
    1. NCT02553122. The combined efficacy of Evicel and tranexamic acid on total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02553122.
NCT02584725 {unpublished data only}
    1. NCT02584725. Tranexamic acid dose and perioperative blood loss in total hip and knee arthroplasty: a prospective, randomized, double-blind tria. clinicaltrials.gov/ct2/show/NCT02584725.
NCT02644473 {published data only}
    1. NCT02644473. Safety of topical tranexamic acid in total joint arthroplasty in high risk patients. clinicaltrials.gov/ct2/show/NCT02644473.
NCT02650856 {published data only}
    1. NCT02650856. Blood loss reduction after total knee arthroplasty. Comparison topical tranexamic acid vs platelet rich plasma. clinicaltrials.gov/ct2/show/NCT02650856.
NCT02687399 {published data only}
    1. NCT02687399. Determine the efficacy of TT-173. Reducing the the total blood loss associated with total knee arthroplasty (HESTAT). clinicaltrials.gov/ct2/show/NCT02687399.
NCT02829346 {published data only}
    1. NCT02829346. Peri-articular tranexamic acid injection in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02829346.
NCT02860221 {published data only}
    1. NCT02860221. Intravenous versus topical administration of low dose epinephrine plus combined administration of intravenous and topical tranexamic acid (TXA) for primary total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02860221.
NCT03019198 {published data only}
    1. NCT03019198. Tranexamic acid in patients undergoing total hip arthroplasty in a Brazilian reference orthopedic center: a randomized controlled trial. clinicaltrials.gov/ct2/show/NCT03019198.
NCT03044041 {published data only}
    1. NCT03044041. Comparison between low dose and high dose intra-articular tranexamic acid in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT03044041.
NCT03074994 {published data only}
    1. NCT03074994. The comparative efficacy of peri-articular and intraarticular tranexamic acid in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT03074994.
NCT03183583 {published data only}
    1. NCT03183583. Tissue adhesive in hip and knee arthroplasty, a cost -effectiveness analysis. clinicaltrials.gov/ct2/show/NCT03183583.
NCT03328832 {published data only}
    1. NCT03328832. Combined topical tranexamic acid with Floseal® in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT03328832.
NCT03359525 {published data only}
    1. NCT03359525. Study comparing topical versus intravenous tranexamic acid in anterior total hip arthroplasty. clinicaltrials.gov/ct2/show/NCT03359525.
NCT03365999 {published data only}
    1. NCT03365999. Oral tranexamic acid vs. oral aminocaproic acid to reduce blood loss and transfusion after total knee replacement. clinicaltrials.gov/ct2/show/NCT03365999.
NCT03690037 {published data only}
    1. NCT03690037. Investigating the effect of intravenous and oral tranexamic acid on blood loss after primary hip and knee arthroplasty (TRAC-24). clinicaltrials.gov/ct2/show/NCT03690037.
Nielsen 2016 {published data only}
    1. Nielsen CS, Jans O, Orsnes T, Foss NB, Troelsen A, Husted H. Combined intra-articular and intravenous tranexamic acid reduces blood loss in total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. Journal of Bone and Joint Surgery 2016;98(10):835-41. - PubMed
NTR6464 Netherlands Trials Register {published data only}
    1. NTR6464. CoKnie. trialsearch.who.int/Trial2.aspx?TrialID=NTR6464 2017.
Ollivier 2016 {published data only}
    1. Ollivier JE, Van Driessche S, Billuart F, Beldame J, Matsoukis J. Tranexamic acid and total hip arthroplasty: optimizing the administration method. Annals of Translational Medicine 2016;4(24):530-3. - PMC - PubMed
Oremus 2014 {published data only}
    1. Oremus K, Sostaric S, Haspl M. Tranexamic acid obviates need for postoperatively salvaged autologous drainage blood retransfusion as part of a blood management programme for total hip and knee arthroplasty. In: European Journal of Anesthesiology. Vol. 30. 2013:6AP3-11.
    1. Oremus K, Sostaric S, Trkulja V, Haspl M. Influence of tranexamic acid on postoperative autologous blood retransfusion in primary total hip and knee arthroplasty: a randomized controlled trial. Transfusion 2014;54(1):31-41. - PubMed
Pachauri 2014 {published data only}
    1. Pachauri A, Acharya KK, Tiwari AK. The effect of tranexamic acid on hemoglobin levels during total knee arthroplasty. Ameroican Journal of Therapeutics 2014;21(5):366-70. - PubMed
Palija 2021 {published data only}
    1. Palija S, Bijeljac S, Manojlovic S, Jovicic Z, Jovanovic M, Cvijic, P et al. Effectiveness of different doses and routes of administration of tranexamic acid for total hip replacement. International Orthopaedics 2021;45(4):865-70. - PubMed
Pathan 2020 {published data only}
    1. Pathan S, Cruz JE, Curtin P. Comparison of the effects of intravenous and oral tranexamic acid on perioperative hemoglobin levels during total knee arthroplasty. Annals of Pharmacotherapy 2020;54(2):138-43. - PubMed
Pavao 2019 {published data only}
    1. Pavao DM, Palhares GM, Albuquerque RSPE, Sousa EB, Barretto JM. Prospective study on the impact of the use of human fibrin sealant free of clot-stabilizing agents in total knee arthroplasty. Revista Brasileira de Ortopedia 2019;54(3):322-8. - PMC - PubMed
Perez‐Jimeno 2018 {published data only}
    1. Perez-Jimeno N, Munoz M, Mateo J, Mayoral AP, Herrera A. Efficacy of topical tranexamic acid within a blood-saving programme for primary total hip arthroplasty: a pragmatic, open-label randomised study. Blood Transfusion 2018;16(6):490-7. - PMC - PubMed
Pinsornsak 2016 {published data only}
    1. Pinsornsak P, Rojanavijitkul S, Chumchuen S. Peri-articular tranexamic acid injection in total knee arthroplasty: a randomized controlled trial. BMC Musculoskeletal Disorders 2016;17:313. - PMC - PubMed
Pinsornsak 2021 {published data only}
    1. Pinsornsak P, Phunphakchit J, Boontanapibul K. Efficacy and systemic absorption of peri-articular versus intra-articular administration of tranexamic acid in total knee arthroplasty: a prospective randomized controlled trial. Arthroplasty Today 2021;11:1-5. - PMC - PubMed
Prakash 2016 {published data only}
    1. Prakash J, Chand S. Topical vs intravenous tranexamic acid in primary total hip arthroplasty: a double-blind, randomized controlled trial. Journal of Arthroplasty 2016;31(4):927-8. - PubMed
Qin 2020 {published data only}
    1. Qin JZ, Wang SJ, Zheng XP, Zhao HH, Lin Y, Shi L et al. Comparison of hemocoagulase atrox versus tranexamic acid used in primary total knee arthroplasty: a randomized controlled trial. Thrombosis Research 2020;188:39-43. - PubMed
Rajesparan 2009 {published data only}
    1. Rajesparan K, Biant LC, Ahmad M, Field RE. The effect of an intravenous bolus of tranexamic acid on blood loss in total hip replacement. Journal of Bone and Joint Surgery 2009;91(6):776-83. - PubMed
Randelli 2010 {published data only}
    1. Randelli F, Banci L, Visentin O, Ragone V, Pavesi M, Randelli G. A randomized prospective double blind controlled trial on effects of fibrin sealant in cementless hip replacement. HIP International 2010;20(3):358.
Randelli 2013 {published data only}
    1. EUCTR2008-002024-28-IT. Quixil validation in hip replacement first implant - ND. trialsearch.who.int/?TrialID=EUCTR2008-002024-28-IT.
    1. Randelli F, Banci L, Ragone V, Pavesi M, Randelli G. Effectiveness of fibrin sealant after cementless total hip replacement: a double-blind randomized controlled trial. International Journal of Immunopathology and Pharmacology 2013;26(1):189-97. - PubMed
Randelli 2014 {published data only}
    1. Randelli F, D'Anchise R, Ragone V, Serrao L, Cabitza P, Randelli P. Is the newest fibrin sealant an effective strategy to reduce blood loss after total knee arthroplasty? A randomized controlled study. Journal of Arthroplasty 2014;29(8):1516-20. - PubMed
Roy 2012 {published data only}
    1. Roy SP, Tanki UF, Dutta A, Jain SK, Nagi ON. Efficacy of intra-articular tranexamic acid in blood loss reduction following primary unilateral total knee arthroplasty. Knee Surgery Sports Traumatology Arthroscopy 2012;20(12):2494-501. - PubMed
Ruiz‐Moyano 1997 {published data only}
    1. Ruíz-Moyano J. Surgery without blood. Aprotinin in hip replacement. Revista Espanola de Anesthesiologia y Reanimacion 1997;44(Suppl 1):117.
Sahin 2019 {published data only}
    1. Sahin IG, Akalin Y, Cevik N, Otuzbir A, Ozkan Y, Ozturk A. Tranexamic acid in total knee replacement which protocol? Which application form? A prospective randomised study. Acta Orthopaedica Belgica 2019;85(4):484-93. - PubMed
Samama 2002 {published data only}
    1. Samama CM, Langeron O, Rosencher N, Capdevila X, Rouche P, Pegoix M, et al. Aprotinin versus placebo in major orthopedic surgery: a randomized, double-blinded, dose-ranging study. Anesthesia and Analgesia 2002;95(2):287-93. - PubMed
Sa‐Ngasoongsong 2011 {published data only}
    1. Sa-Ngasoongsong P, Channoom T, Kawinwonggowit V, Woratanarat P, Chanplakorn P, Wibulpolprasert B et al. Postoperative blood loss reduction in computer-assisted surgery total knee replacement by low dose intra-articular tranexamic acid injection together with 2-hour clamp drain: A prospective triple-blinded randomized controlled trial. Orthopedic Reviews 2011;3(e12):51-6. - PMC - PubMed
Sa‐Ngasoongsong 2013 {published data only}
    1. Sa-Ngasoongsong P, Wongsak S, Chanplakorn P, Woratanarat P, Wechmongkolgorn S, Wibulpolprasert B, et al. Efficacy of low-dose intra-articular tranexamic acid in total knee replacement; a prospective triple-blinded randomized controlled trial. BMC Musculoskeletal Disorders 2013;14(340):1-8. - PMC - PubMed
Seol 2016 {published data only}
    1. Seol YJ, Seon JK, Lee SH, Jin C, Prakash J, Park YJ, et al. Effect of tranexamic acid on blood loss and blood transfusion reduction after total knee arthroplasty. Knee Surgery and Related Research 2016;28(3):188-93. - PMC - PubMed
Seviciu 2016 {published data only}
    1. Seviciu A, Gross I, Fathima S, Walsh SM. Effects of tranexamic acid and bipolar sealer alone or in combination in primary total knee arthroplasty: a prospective, randomized, controlled trial. Arthroplasty Today 2016;2(2):77-82. - PMC - PubMed
Shah 2006 {published data only}
    1. Shah N, Wadia F, Frayne M, Pendry K, Porter M. Tranexamic acid in revision hip arthroplasty. British Hip Society 2006;88-B(Suppl II):239-23d.
Shihab 2021 {published data only}
    1. Shihab EM, Shareef SM, Abbas SN, Wahhab MS, Yaseen NN. Efficacy of combined use of intravenous and topical versus only topical tranexamic acid in primary total knee arthroplasty. International Journal of Pharmaceutical Research 2021;13(2):4448-53.
Skovgaard 2013 {published data only}
    1. Skovgaard C, Holm B, Troelsen A, Lunn TH, Gaarn-Larsen L, Kehlet H, et al. No effect of fibrin sealant on drain output or functional recovery following simultaneous bilateral total knee arthroplasty: a randomized, double-blind, placebo-controlled study. Acta Orthopaedica 2013;84(2):153-8. - PMC - PubMed
SouzaNeto 2020 {published data only}
    1. Souza Neto EP, Usandizaga G. Comparison of two doses of intra-articular tranexamic acid on postoperative bleeding in total knee arthroplasty: a randomized clinical trial. Brazilian Journal of Anesthesiology 2020;70(4):318-24. - PMC - PubMed
Stutz 2004 {published data only}
    1. Stutz H, Hempelmann HCG. The use of autologous fibrin glue to reduce perioperative blood loss in total knee arthroplasty - results of a controlled study. Orthopädische Praxis 2004;40(12):1-3.
Suarez 2014 {published data only}
    1. Suarez JC, Slotkin EM, Alvarez AM, Szubski CR, Barsoum WK, Patel PD. Prospective, randomized trial to evaluate efficacy of a thrombin-based hemostatic agent in total knee arthroplasty. The Journal of Arthroplasty 2014;29(10):1950-5. - PubMed
Subramanyam 2018 {published data only}
    1. Subramanyam KN, Khanchandani P, Tulajaprasad PV, Jaipuria J, Mundargi AV. Efficacy and safety of intra-articular versus intravenous tranexamic acid in reducing perioperative blood loss in total knee arthroplasty: a prospective randomized double-blind equivalence trial. The Bone and Joint Journal 2018;100:152-60. - PubMed
Tammachote 2019 {published data only}
    1. Tammachote N, Raphiphan R, Kanitnate S. High-dose (3 g) topical tranexamic acid has higher potency in reducing blood loss after total knee arthroplasty compared with low dose (500 mg): a double-blind randomized controlled trial. European Journal of Orthopaedic Surgery & Traumatologie 2019;29(8):1729-35. - PubMed
Tandogan 2021 {published data only}
    1. Tandogan RN, Polat M, Beyzadeoglu T, Karabulut E, Yildirim K, Kayaalp A. Topical co-delivery of platelet rich fibrin and tranexamic acid does not decrease blood loss in primary total knee arthroplasty compared to the standard of care: a prospective, randomized, controlled trial. Knee Surgery, Sports Traumatology, Arthroscopy 2021;29(2):519-28. - PubMed
Tavares Sanchez‐Monge 2018 {published data only}
    1. Tavares Sanchez-Monge FJ, Aguado Maestro I, Banuelos Diaz A, Martin Ferrero MA, Garcia Alonso MF. Efficacy and safety of the topical application of tranexamic acid in primary cementless hip arthroplasty: prospective, randomised, double-blind and controlled study [Eficacia y seguridad de la aplicacion del acido tranexamico topico en la artroplastia primaria no cementada de cadera: estudio prospectivo, aleatorizado, doble ciego y controlado]. Revista Española de Cirugía Ortopédica y Traumatología 2018;62(1):47-54. - PubMed
TCTR20170503003 Thai Clinical Trials Registry {published data only}
    1. TCTR20170503003. Comparison on the effectiveness of regimens with combination of intravenous and intra-articular applications of tranexamic acid for the significant reduction of blood loss in primary knee osteoarthritis undergoing total knee arthroplasty: a randomized clinical trial study. www.thaiclinicaltrials.org/.
TCTR20170618001 Thai Clinical Trials Registry {published data only}
    1. TCTR20170618001. Blood loss reduction: effect of tranexamic acid routes in different knee prosthesis: a randomized controlled trial. www.thaiclinicaltrials.org/ 2017.
TCTR20200511002 {published data only}
    1. TCTR20200511002. Effectiveness of intraosseous tranexamic acid combined with intravenous tranexamic acid in hip arthroplasty. www.thaiclinicaltrials.org/show/TCTR20200511002 2020.
Thipparampall 2017 {published data only}
    1. Thipparampall AK, Gurajala I, Gopinath R. The effect of different dose regimens of tranexamic acid in reducing blood loss during hip surger. Indian Journal Anaesthesiology 2017;61(3):235-9. - PMC - PubMed
Thorpe 1994 {published data only}
    1. Thorpe CM, Murphy WG, Logan M. Use of aprotinin in knee replacement surgery. British Journal of Anaesthesia 1994;73(3):408-10. - PubMed
Torkaman 2020 {published data only}
    1. Torkaman A, Rostami A, Sarshar MR, Akbari Aghdam H, Motaghi P, Yazdi H. The efficacy of intravenous versus topical use of tranexamic acid in reducing blood loss after primary total knee arthroplasty: a randomized clinical trial. Archives of Bone & Joint Surgery 2020;8(3):363-7. - PMC - PubMed
Tripathy 2020 {published data only}
    1. Tripathy SK, Rao PB, Nanda SN, Nayak C, Samal BP, Jain M, et al. Safety and efficacy of epsilon aminocaproic acid (EACA) as an antihemorrhagic drug in bilateral one stage total knee arthroplasty: a double-blind randomized controlled trial. Knee 2020;27(1):229-34. - PubMed
Tzatzairis 2016 {published data only}
    1. NCT03656445. Tranexamic acid in total knee replacement. clinicaltrials.gov/ct2/show/NCT03656445.
    1. Tzatzairis TK, Drosos GI, Kotsios SE, Ververidis AN, Vogiatzaki TD, Kazakos KI. Intravenous vs topical tranexamic acid in total knee arthroplasty without tourniquet application: a randomized controlled study. Journal of Arthroplasty 2016;31(11):2465-70. - PubMed
U1111‐1172‐0797 Brazilian Clinical Trials Registry {published data only}
    1. U1111-1172-0797. Tranexamic acid in primary non-cemented total hip arthroplasty [Acido Tranexâmico em artroplastia total primária não-cimentada de quadril]. ensaiosclinicos.gov.br/rg/RBR-75bwry.
U1111‐1187‐8385 Brazilian Clinical Trials Registry {published data only}
    1. U1111-1187-8385. Platelet rich plasma (PRP) and tranexamic acid (TXA) applied in total knee arthroplasty [Plasma Rico em Plaquetas (PRP) e Ácido Tranexâmico (ATN) aplicados na artroplastia total do joelho]. ensaiosclinicos.gov.br/trial/4514/1.
U1111‐1207‐0408 Brazilian Clinical Trials Registry {published data only}
    1. U1111-1207-0408. Epsilon aminocaproic acid(EACA) and tranexamic acid(TXA) in total knee arthroplasty [Ácido Épsilon Aminocapróico(AEAC) e Ácido Tranexâmico(ATX) na Artroplastia Total do Joelho]. ensaiosclinicos.gov.br/rg/RBR-4c6s7s.
Van Elst 2013 {published data only}
    1. NCT01622946. The effect of topical application of tranexamic acid in total hip arthroplasty through the direct anterior approach. clinicaltrials.gov/ct2/show/NCT01622946 2012.
    1. Van Elst C, Vanbiervliet J, Simon JP, Corten K. The effect of topical application of tranexamic acid in total hip arthroplasty through the direct anterior apporach. In: American Academy of Orthopaedic Surgeons. 2013:P093.
Vela 2012 {published data only}
    1. Vela E, Alvarez JC, Vollmer I, Maiques J, Puig L, Santiveri FX. Tranexamic acid reduces blood transfusion without increases in thrombotic complications in joint replacement surgery. In: European Journal of Anesthesiology. Vol. 50. 2012:6AP2-6.
Wang 2001 {published data only}
    1. Wang GJ, Hungerford DS, Savory CG, Rosenberg AG, Mont MA, Burks SG, et al. Use of fibrin sealant to reduce bloody drainage and hemoglobin loss after total knee arthroplasty: a brief note on a randomized prospective trial. Journal of Bone and Joint Surgery 2001;83-A(10):1503-4. - PubMed
Wang 2003 {published data only}
    1. Wang GJ, Goldthwaite CAJr, Burks SG, Spotnitz WD. Experience improves successful use of fibrin sealant in total knee arthroplasty: implications for surgical education. Journal of Long-term Effects of Medical Implants 2003;13(5):389-97. - PubMed
Wang 2017a {published data only}
    1. Wang JW, Chen B, Lin PC, Yen SH, Huang CC, Kuo FC. The efficacy of combined use of rivaroxaban and tranexamic acid on blood conservation in minimally invasive total knee arthroplasty a double-blind randomized, controlled trial. Journal of Arthroplasty 2017;32(3):801-6. - PubMed
Wang 2018a {published data only}
    1. Wang D, Luo ZY, Yu ZP, Liu LX, Chen C, Meng WK, et al. The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial. Journal of Thrombosis and Haemostasis 2018;16(12):2442-53. - PubMed
Wang 2018b {published data only}
    1. Wang D, Wang HY, Cao C, Li LL, Meng WK, Pei FX, et al. Tranexamic acid in primary total knee arthroplasty without tourniquet: a randomized, controlled trial of oral versus intravenous versus topical administration. Nature 2018;8(1):1-9. - PMC - PubMed
Wang 2018c {published data only}
    1. Wang D, Zhu H, Meng WK, Wang HY, Luo ZY, Pei FX, et al. Comparison of oral versus intra-articular tranexamic acid in enhanced-recovery primary total knee arthroplasty without tourniquet application: a randomized controlled trial. BMC Musculoskeletal Disorders 2018;19(1):85. - PMC - PubMed
Wei 2018 {published data only}
    1. Wei W, Dang S, Duan D, Wei L. Comparison of intravenous and topical tranexamic acid in total knee arthroplasty. BMC Musculoskeletal Disorders 2018;19(1):191. - PMC - PubMed
Wollinsky 1991 {published data only}
    1. Wollinsky KH, Mehrkens HH, Freytag T, Geiger P, Weindler M. Does aprotinin lessen intraoperative blood loss? Ansthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 1991;26(4):208-10. - PubMed
Wong 2010 {published data only}
    1. Abrishami A, Wong J, El-Beheiry H, Hasan SM, Chung F. Intra-articular application of tranexamic acid for perioperative blood loss in total knee arthroplasty: a randomized controlled trial. Canadian Journal of Anesthesia 2009;56:S138.
    1. Abrishami A. Timing and volume of topical tranexamic acid administration for postoperative blood loss in total knee arthroplasty. In: Canadian Journal of Anesthesia. Vol. 57. 2010:S142-3.
    1. Wong J, Abrishami A, De Silva Y, Hasan SM, Mahomed N, Chung F. A randomized controlled trial of topical tranexamic acid for postoperative blood loss in total knee arthroplasty. Anesthesia and Analgesia 2009;108:S-22.
    1. Wong J, Abrishami A, El Beheiry H, Mahomed NN, Roderick Davey J, Gandhi, R, et al. Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. Journal of Bone and Joint Surgery 2010;92(15):2503-13. - PubMed
Xu 2015 {published data only}
    1. Xu X, Li X, Liu W, Wang Z. Longtime soaking of high concentration tranexamic acid in total hip arthroplasty: a prospective randomized controlled trial in 224 patients. Pakistani Journal of Medical Science 2015;31(6):1306-11. - PMC - PubMed
Yi 2016 {published data only}
    1. Yi Z, Bin S, Jing Y, Zongke Z, Pengde K, Fuxing P. Tranexamic acid administration in primary total hip arthroplasty: a randomized controlled trial of intravenous combined with topical versus single-dose intravenous administration. Journal of Bone and Joint Surgery 2016;98(12):983-91. - PubMed
Yuan 2017 {published data only}
    1. Yuan X, Li B, Wang Q, Zhang X. Comparison of 3 routes of administration of tranexamic acid on primary unilateral total knee arthroplasty: a prospective, randomized, controlled study. Journal of Arthroplasty 2017;32(9):2738-43. - PubMed
Yuan 2018 {published data only}
    1. Yuan X, Wang J, Wang Q, Zhang X. Synergistic effects of intravenous and intra-articular tranexamic acid on reducing hemoglobin loss in revision total knee arthroplasty: a prospective, randomized, controlled study. Transfusion 2018;58(4):982-8. - PubMed
Zecker 2016 {published data only}
    1. Zekcer A, Del Priori R, Tieppo C, da Silva RS, Severino NR. Topical vs. Intravenous administration of tranexamic acid in knee arthroplasty and prevalence of deep venous thrombosis: a randomized clinical trial. Journal of Vascular Brasillia 2016;15(2):120-5. - PMC - PubMed
Zecker 2017 {published data only}
    1. Zekcer A, Del Priori R, Tieppo C, da Silva RS, Severino NR. Comparative study of topical vs. intravenous tranexamic acid regarding blood loss in total knee arthroplasty. Revista Brasileria de Ortopedia 2017;52(5):589-95. - PMC - PubMed
Zeng 2018a {published data only}
    1. Zeng WN, Liu JL, Wang FY, Chen C, Zhou Q, Yang L. Low-dose epinephrine plus tranexamic acid reduces early postoperative blood loss and inflammatory response: a randomized controlled trial. Journal of Bone and Joint Surgery 2018;100(4):295-304. - PubMed
Zhang 2020c {published data only}
    1. Zhang S, Xu H, Xie J, Cao G, Lei Y, Pei F. Tranexamic acid attenuates inflammatory effect and modulates immune response in primary total knee arthroplasty: a randomized, placebo-controlled, pilot trial. Inflammopharmacology 2020;28(4):839-49. - PubMed
Zhang 2021 {published data only}
    1. Zhang S, Wang F, Wang C, Chu P, Shi L, Xue Q. Are the applications of tranexamic acid in reverse hybrid total knee arthroplasty (TKA) the same as those in fully cemented TKA?: A randomized controlled trial. Advances in Therapy 2021;38(5):2542-57. - PubMed
Zhang 2021a {published data only}
    1. Zhang, S, Xie J, Cao G, Lei Y, Huang Q, Pei F. Six-dose intravenous tranexamic acid regimen further inhibits postoperative fibrinolysis and reduces hidden blood loss following total knee arthroplasty. Journal of Knee Surgery 2021;34(2):224-32. - PubMed
Zhou 2018 {published data only}
    1. Zhou KD, Wang HY, Wang Y, Liu ZH, He C, Feng JM. Is topical or intravenous tranexamic acid preferred in total hip arthroplasty? A randomized, controlled, noninferiority clinical trial. Plos One 2018;13(10):1-13. - PMC - PubMed
Zufferey 2017 {published data only}
    1. Zufferey PJ, Lanoiselee, J, Chapelle C, Borisov DB, Bien JY, Lambert P. Intravenous tranexamic acid bolus plus infusion is not more effective than a single bolus in primary hip arthroplasty: a randomized controlled trial. Anesthesiology 2017;127(3):413-22. - PubMed

References to studies awaiting assessment

Abdallah 2020 {published data only}
    1. Abdallah AA, Sallam AA, Arafa MS, Henawy AT. Topical tranexamic acid in total knee arthroplasty: does it augment the effect of the intravenous administration in patients with moderate-to-high risk of bleeding? a randomized clinical trial. Journal of Knee Surgery 2021;34(14):1570-8. - PubMed
Adravanti 2018 {published data only}
    1. Adravanti P, Di Salvo E, Calafiore G, Vasta S, Ampollini A, Rosa MA. A prospective, randomized, comparative study of intravenous alone and combined intravenous and intraarticular administration of tranexamic acid in primary total knee replacement. Arthroplasty Today 2017;Not stated:Not stated. - PMC - PubMed
    1. Adravanti P, Di Salvo E, Calafiore G, Vasta S, Ampollini A, Rosa MA. A prospective, randomized, comparative study of intravenous alone and combined intravenous and intraarticular administration of tranexamic acid in primary total knee replacement. Arthroplasty Today 2018;4(1):85-8. - PMC - PubMed
Aggarwal 2016 {published data only}
    1. Aggarwal AK, Singh N, Sudesh P. Topical vs intravenous tranexamic acid in reducing blood loss after bilateral total knee arthroplasty: a prospective study. Journal of Arthroplasty 2016;31(7):1442-8. - PubMed
Alipour 2013 {published data only}
    1. Alipour M, Tabari M, Keramati M, Zarmehri AM, Makhmalbaf H. Effectiveness of oral tranexamic acid administration on blood loss after knee artroplasty: a randomized clinical trial. Transfusion and Apheresis Science 2013;49(3):574-7. - PubMed
Almeida 2018 {published data only}
    1. Almeida MDC, Albuquerque RPE, Palhares GM, Almeida JPC, Barretto JM, Cavanellas N. Evaluation of the use of tranexamic acid in total knee arthroplasty. Revista Brasileira de Ortopedia 2018;53(6):761-7. - PMC - PubMed
Amin 2020 {published data only}
    1. Amin MS, Habib MK, Rehman AU. Comparison of blood loss between intra-articular and intra-venous administration of tranexamic acid in primary total knee arthroplasty. SICOT-J 2020;6(20):1-5. - PMC - PubMed
Anon 2016 {published data only}
    1. Anon. Comparison of perioperative blood loss and transfusion rate in primary unilateral total hip arthroplasty by topical, intravenous application or combined application of tranexamic acid. Chinese Journal of Tissue Engineering Research 2016;20(4):459-64.
Antinolfi 2014 {published data only}
    1. Antinolfi P, Innocenti B, Caraffa A, Cerulli G. Blood loss in total knee arthroplasty: Mechanical vs pharmacological approach. In: 23rd National Congress of the Italian Society of Young Surgeon (SPIGC). Vol. 45(3-4). 2010:293.
    1. Antinolfi P, Innocenti B, Caraffa A, Peretti G, Cerulli G. Post-operative blood loss in total knee arthroplasty: knee flexion versus pharmacological techniques. Knee Surgery, Sports Traumatology, Arthroscopy 2014;22(11):2756-62. - PubMed
Arora 2018 {published data only}
    1. Arora M, Singh S, Gupta V, Dongre A, Shetty V. Comparing the efficacy of intravenous or intra-articular tranexamic acid in reducing blood loss in simultaneous bilateral knee replacement surgery without the use of tourniquet. European Journal of Orthopaedic Surgery and Traumatology 2018;28(7):1417-20. - PubMed
Arslan 2018 {published data only}
    1. Arslan A, Gormeli G. Using intra-articular tranexamic acid in total knee replacement surgery with and without bleeding control: a prospective randomized double blind study. European Review for Medical and Pharmacological Sciences 2018;22(18):6127-32. - PubMed
Bae 2014 {published data only}
    1. Bae KC, Cho CH, Lee KJ, Son ES, Lee SW, Lee SJ, et al. Efficacy of intra-articular injection of thrombin-based hemostatic agent in the control of bleeding after primary total knee arthroplasty. Knee Surgery and Related Research 2014;26(4):236-40. - PMC - PubMed
Balasubramanian 2016 {published data only}
    1. Balasubramanian N, Natarajan GB, Prakasam S. Prospective study to compare intra-articular versus intravenous tranexemic acid in reducing post-operative blood loss in staged bilateral total knee arthroplasty. Malaysian Orthopaedic Journal 2016;10(3):7-11. - PMC - PubMed
Bao 2019 {published data only}
    1. Bao HB, Sun L, Tian XB, Chen L, Li SL, Yang XT, et al. Relationship between intra-articular infusion combined with peri-articular injection of tranexamic acid and postoperative blood loss after total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2019;23(36):5747-52.
Bidolegui 2014 {published data only}
    1. Bidolegui F, Arce G, Lugones A, Pereira S, Vindver G. Tranexamic acid reduces blood loss and transfusion in patients undergoing total knee arthroplasty without tourniquet: a prospective randomized controlled trial. Open Orthopaedics Journal 2014;8:250-4. - PMC - PubMed
Borisov 2011 {published data only}
    1. Borisov D, Yudin S, Krylov O, Markov B, Istomina N. Tranexamic acid in hip arthroplasty: a dose-response study. Transfusion and Haemostasis 2011;48:88.
Bowman 2018 {published data only}
    1. Bowman EN, McCabe MP, Cleveland KB. Effectiveness of thrombin-collagen and autologous platelet-rich plasma in total hip arthroplasty hemostasis: a prospective, randomized, controlled trial. Journal of Surgical Orthopaedic Advances 2018;27(2):136-41. - PubMed
Bradshaw 2012 {published data only}
    1. Bradshaw AR, Monoghan J, Campbell D. Oral tranexamic acid reduces blood loss in total knee replacement arthroplasty. Current Orthopaedic Practice 2012;23(3):209-12.
Canata 2012 {published data only}
    1. Canata GL, Casale V, Chiey A. Management of post-operative pain and bleeding in knee replacements. Journal of Orthopaedics and Traumatology volume 2012;13(Suppl 1):S30-1.
Cankaya 2017 {published data only}
    1. Cankaya D, Dasar U, Satilmis AB, Basaran SH, Akkaya M, Bozkurt M. The combined use of oral and topical tranexamic acid is a safe, efficient and low-cost method in reducing blood loss and transfusion rates in total knee arthroplasty. Journal of Orthopaedic Surgery 2017;25(1):1-6. - PubMed
Carvalho 2015 {published data only}
    1. Carvalho LH Jr, Frois Temponi E, Machado Soares LF, Goncalves MB, Paiva Costa L, Tavares de Souza ML. Bleeding reduction after topical application of tranexamic acid together with betadine solution in total knee arthroplasty. A randomised controlled study. Orthopaedics & Traumatology: Surgery and Research 2015;101(1):83-7. - PubMed
Castro‐Menendez 2016 {published data only}
    1. Castro-Menendez M, Pena-Paz S, Rocha-Garcia F, Rodriguez-Casas N, Huici-Izco R, Montero-Vieites A. Efficacy of 2 grammes of intravenous transexamic acid in the reduction of post-surgical bleeding after total hip and knee replacement. Revista Española de Cirugía Ortopédica y Traumatología 2016;60(5):315-24. - PubMed
Cavusoglu 2015 {published data only}
    1. Cavusoglu AT, Ayanoglu T, Esen E, Atalar H, Turanli S. is intraarticular administration of tranexamic acid efficient and safe as systemic administration in total knee arthroplasty? Single center, randomized, controlled trial. Eklem Hastalık Cerrahisi 2015;26(3):164-7. - PubMed
Chai 2015 {published data only}
    1. Chai XY, Su CZ, Pang T, Lv D, Zhu B, Hou ZY, et al. Effects of intravenous versus topical application of tranexamic acid on blood loss following total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2015;19(35):5604-9.
Chen 2016a {published data only}
    1. Chen JY, Chin PL, Moo IH, Pang HN, Tay DK, Chia SL, et al. Intravenous versus intra-articular tranexamic acid in total knee arthroplasty: a double-blinded randomised controlled noninferiority trial. The Knee 2016;23(1):152-6. - PubMed
Chen 2018 {published data only}
    1. Chen GH, Qin L, Huang H, Wang Z, Ma JC, Xu Y. Intravenous versus articular injection of tranexamic acid for reducing hemorrhage after unilateral total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2018;22(3):351-5.
ChiCTR1800015834 {published data only}
    1. ChiCTR1800015834. Efficacy of tranexamic acid combined with carbazochrome sodium sulfonate on blood loss in primary total hip arthroplasty using a direct anterior approach: a prospective randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=26931 2018.
ChiCTR1900026092 {published data only}
    1. ChiCTR1900026092. Effects of tranexamic acid combined with dexamethasone on perioperative inflammatory response and fibrinolytic system in total knee arthroplasty: a prospective randomized controlled study. www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR1900026092.
ChiCTR1900027416 {published data only}
    1. ChiCTR1900027416. Effects of tranexamic acid and dexamethasone on immune function and complement in patients undergoing total hip replacement: a randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=45688 2019.
ChiCTR2000032271 {published data only}
    1. ChiCTR2000032271. Epsilon-aminocaproic acid versus tranexamic acid in reducing blood loss in total hip/knee arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=52241 2020.
ChiCTR‐INR‐16010188 {published data only}
    1. ChiCTR-INR-16010188. Intravenous remedial application of tranexamic acid enhanced recovery after surgery to reduce postoperative hidden hemorrhage and inflammatory reaction-a prospective randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=17351 2016.
ChiCTR‐INR‐16010270 {published data only}
    1. ChiCTR-INR-16010270. Peri-articular tranexamic acid injection in total knee/hip arthroplasty: a prospective randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=17193 2016.
ChiCTR‐INR‐17010951 {published data only}
    1. ChiCTR-INR-17010951. Effects of knee position and tranexamic acid in primary total knee arthroplasty: a randomized, controlled trial. www.chictr.org.cn/showprojen.aspx?proj=18630 2017.
ChiCTR‐IOR‐15007198 {published data only}
    1. ChiCTR-IOR-15007198. Influence of intravenous and topical application of tranexamic acid on postoperative blood loss and VTE in primary total knee arthroplasty: a prospective randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=12138 2015.
ChiCTR‐IPR‐17011848 {published data only}
    1. ChiCTR-IPR-17011848. The clinical effect of oral tranexamic acid in peri-operative period of total knee arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=19894 2017.
ChiCTR‐IPR‐17012265 {published data only}
    1. ChiCTR-IPR-17012265. Blood-sparing efficacy of multiple doses of oral tranexamic acid administration in enhanced-recovery primary total knee arthroplasty: a randomized controlled trial. www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-IPR-17012265.
CTRI/2018/02/012030 {published data only}
    1. CTRI/2018/02/012030. Trial to compare efficiency of a drug used to reduce blood loss in surgical procedures when given through veins before start of surgery versus when sprayed at the site of surgery. www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=23219&EncHid... 2018.
CTRI/2018/05/013588 {published data only}
    1. CTRI/2018/05/013588. A trial to compare efficiency of a drug used to reduce blood loss in surgical procedures when given through veins at different timings before, during and after surgery. trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2018/05/013588 2018.
CTRI/2018/08/015421 {published data only}
    1. CTRI/2018/08/015421. Role of tranexamic acid in reducing blood loss in total hip replacement surgeries. trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2018/08/015421 (first received 2018).
CTRI/2019/01/017105 {published data only}
    1. CTRI/2019/01/017105. To assess the effect of the drug tranexamic acid on the blood loss and rate of blood transfusion by infiltrating it into the joint and by giving it directly into the vein in patients undergoing total knee replacement surgery. www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=30550&EncHid... 2019.
CTRI/2019/09/021302 {published data only}
    1. CTRI/2019/09/021302. To use a drug tranexamic acid to reduce blood loss during femur and hip surgeries. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=26588&EncHid=&u... 2019.
CTRI/2021/09/036855 {published data only}
    1. CTRI/2021/09/036855. The efficacy of tranexamic acid which is a drug that promotes clotting of blood, in preventing blood loss in patients undergoing surgeries in and around hip joint. trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2021/09/036855.
DiFrancesco 2013 {published data only}
    1. Di Francesco A, Flamini S, Fiori F, Mastri F. Hemostatic matrix effects on blood loss after total knee arthroplasty: a randomized controlled trial. Indian Journal of Orthopaedics 2013;47(5):474-81. - PMC - PubMed
Digas 2015 {published data only}
    1. Antonopoulou E, Digas G, Meletiadis G, Koutsogiannis I, Netzadin N, Tanasidis A. The effectiveness of tranexamic acid in total knee replacement. Regional Anaesthesia & Pain Therapy (ESRA) Congress 2013;38(5 Suppl 1):E177.
    1. Digas G, Koutsogiannis I, Meletiadis G, Antonopoulou E, Karamoulas V, Bikos C. Intra-articular injection of tranexamic acid reduce blood loss in cemented total knee arthroplasty. European Journal of Orthopaedic Surgery and Traumatology 2015;25(7):1181-8. - PubMed
EUCTR‐2013‐003169‐33‐DK {published data only}
    1. EUCTR-2013-003169-33-DK. Evaluation of intra articular tranexamic acid for reduction of total blood loss in total knee unilateral arthroplasty. www.clinicaltrialsregister.eu/ctr-search/trial/2013-003169-33/DK 2013.
Falez 2013 {published data only}
    1. Falez F, Meo A, Panegrossi G, Favetti F, La Cava F, Casella F. Blood loss reduction in cementless total hip replacement with fibrin spray or bipolar sealer: a randomised controlled trial on ninety five patients. International Orthopaedics 2013;37(7):1213-7. - PMC - PubMed
Fleischmann 2011 {published data only}
    1. Fleischmann F, Matuschek C, Orth K, Gerber PA, Knoefel WT, Peiper M, et al. Aprotinin and classic wound drainage are unnecessary in total hip replacement-a prospective randomized trial. European Journal of Medical Research 2011;17:21. - PMC - PubMed
    1. Fleischmann F, Matuschek C, Orth K, Gerber PA, Mota R, Knoefel WT, et al. Aprotinin and classic wound drainage are unnecessary in total hip replacement - a prospective randomized trial. European Journal of Medical Research 2011;16(1):20-8. - PMC - PubMed
Gautam 2011 {published data only}
    1. Gautam PL, Katyal S, Yamin M, Singh A. Effect of tranexamic acid on blood loss and transfusion requirement in total knee replacement in the Indian population: a case series. Indian Journal of Anaesthesia 2011;55(6):590-3. - PMC - PubMed
Gautam 2013 {published data only}
    1. Gautam VK, Sambandam B, Singh S, Gupta P, Gupta R, Maini L. The role of tranexamic acid in reducing blood loss in total knee replacement. Journal of Clinical Orthopaedics and Trauma 2013;4(1):36-9. - PMC - PubMed
Gomez Barbero 2019 {published data only}
    1. Gomez Barbero P, Gomez Aparicio MS, Blas Dobon JA, Pelayo de Tomas JM, Morales Suarez-Varela M, Rodrigo Perez JL. Which route of administration of acid tranexamic, intravenous or intra-articular, is more effective in the control of post-surgical bleeding after a total hip arthroplasty? A prospective, controlled and randomized study. Revista Espanola De Cirugia Ortopedica Y Traumatologia 2019;63(2):138-45. - PubMed
Gulabi 2019 {published data only}
    1. Gulabi D, Yuce Y, Erkal KH, Saglam N, Camur S. The combined administration of systemic and topical tranexamic acid for total hip arthroplasty: is it better than systemic? Acta Orthopaedica et Traumatologica Turcica 2019;53(4):297-300. - PMC - PubMed
Guzel 2016 {published data only}
    1. Guzel Y, Gurcan OT, Golge UH, Dulgeroglu TC, Metineren H. Topical tranexamic acid versus autotransfusion after total knee arthroplasty. Journal of Orthopaedic Surgery 2016;24(2):179-82. - PubMed
Hongshun 2019 {published data only}
    1. Hongshun Z, Jiancuo A, Shunhong G, Yonggang L, Liping G. Intraoperative and postoperative blood loss and levels of c-reactive protein and interleukin-6 after local application of tranexamic acid in total hip arthroplasty. Chinese Journal of Tissue Engineering Research 2019;23(4):493-8.
Hou 2015 {published data only}
    1. Hou ZY, Su CZ, Pang T, Lv D, Zhu B, Sun YL, et al. Primary unilateral cemented total knee arthroplasty: effect of tranexamic acid usage on blood loss. Chinese Journal of Tissue Engineering Research 2015;19(9):1329-34.
Hsu 2015 {published data only}
    1. Hsu CH, Lin PC, Kuo FC, Wang JW. A regime of two intravenous injections of tranexamic acid reduces blood loss in minimally invasive total hip arthroplasty: a prospective randomised double-blind study. The Bone & Joint Journal 2015;97-B(7):905-10. - PubMed
Hu 2018 {published data only}
    1. Hu W-H. Efficacy of intravenous versus topical administration of tranexanmic acid in primary total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2018;22(3):356-61.
Huang 2014 {published data only}
    1. Huang Z, Ma J, Shen B, Pei F. Combination of intravenous and topical application of tranexamic acid in primary total knee arthroplasty: a prospective randomized controlled trial. The Journal of Arthroplasty 2014;29(12):2342-6. - PubMed
Imai 2012 {published data only}
    1. Imai N, Dohmae Y, Suda K, Miyasaka D, Ito T, Endo N. Tranexamic acid for reduction of blood loss during total hip arthroplasty. Journal of Arthroplasty 2012;27(10):1838-43. - PubMed
IRCT20120910010800N3 {published data only}
    1. Determining the preventive effect of venous fibrinogen on the amount of bleeding during hip arthroplasty surgery. en.irct.ir/trial/62685.
Jain 2016 {published data only}
    1. Jain NP, Nisthane PP, Shah NA. Combined administration of systemic and topical tranexamic acid for total knee arthroplasty: can it be a better regimen and yet safe? A randomized controlled trial. Journal of Arthroplasty 2016;31(2):542-7. - PubMed
Jaszczyk 2015 {published data only}
    1. Jaszczyk M, Kozerawski D, Kolodziej L, Kazimierczak A, Sarnecki P, Sieczka L. Effect of single preoperative dose of tranexamic acid on blood loss and transfusion in hip arthroplasty. Ortopedia, Traumatologia, Rehabilitacja 2015;17(3):265-73. - PubMed
Jia 2019 {published data only}
    1. Jia J. Combined use of intravenous and topical tranexamic acid in patients aged over 70 years old undergoing total hip arthroplasty. Journal of Orthopaedic Surgery 2019;14(1):345. - PMC - PubMed
Karaaslan 2015 {published data only}
    1. Karaaslan F, Karaoglu S, Mermerkaya MU, Baktir A. Reducing blood loss in simultaneous bilateral total knee arthroplasty: combined intravenous-intra-articular tranexamic acid administration. A prospective randomized controlled trial. The Knee 2015;22(2):131-5. - PubMed
    1. Karaaslan F, Mermerkaya MU, Karaoglu S, Baktir A. Reducing blood loss in simultaneous bilateral total knee arthroplasty: combined intravenous intra-articular tranexamic acid administration. Orthopaedic Journal of Sports Medicine 2014;2(11):Suppl 3. - PubMed
Kazemi 2010 {published data only}
    1. Kazemi SM, Mosaffa F, Eajazi A, Kaffashi M, Daftari Besheli L, Bigdeli MR, et al. The effect of tranexamic acid on reducing blood loss in cementless total hip arthroplasty under epidural anesthesia. Orthopedics 2010;33(1):17-22. - PubMed
Keyhani 2016 {published data only}
    1. Keyhani S, Esmailiejah AA, Abbasian MR, Safdari F. Which route of tranexamic acid administration is more effective to reduce blood loss following total knee arthroplasty? Archives of Bone & Joint Surgery 2016;4(1):65-9. - PMC - PubMed
Kim 2014 {published data only}
    1. Kim TK, Chang CB, Kang YG, Seo ES, Lee JH, Yun JH, et al. Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial. Knee Surgery, Sports Traumatology, Arthroscopy 2014;22(8):1870-8. - PubMed
Kundu 2015 {published data only}
    1. Kundu R, Das A, Basunia SR, Bhattacharyya T, Chattopadhyay S, Mukherjee A. Does a single loading dose of tranexamic acid reduce perioperative blood loss and transfusion requirements after total knee replacement surgery? A randomized, controlled trial. Journal of Natural Science, Biology and Medicine 2015;6(1):94-9. - PMC - PubMed
Kusuma 2013 {published data only}
    1. Kusuma SK, Sheridan KC, Wasielewski RC. Use of bovine thrombin to reduce blood loss in primary total knee arthroplasty: a controlled randomized trial. Journal of Arthroplasty 2013;28(8):1278-81. - PubMed
Lacko 2017 {published data only}
    1. Lacko M, Cellar R, Schreierova D, Vasko G. Comparison of intravenous and intra-articular tranexamic acid in reducing blood loss in primary total knee replacement. Eklem Hastalik Cerrahisi 2017;28(2):64-71. - PubMed
Lee 2013 {published data only}
    1. Lee YC, Park SJ, Kim JS, Cho CH. Effect of tranexamic acid on reducing postoperative blood loss in combined hypotensive epidural anesthesia and general anesthesia for total hip replacement. Journal of Clinical Anesthesia 2013;25(5):393-8. - PubMed
Lee 2013a {published data only}
    1. Lee SH, Cho KY, Khurana S, Kim KI. Less blood loss under concomitant administration of tranexamic acid and indirect factor xa inhibitor following total knee arthroplasty: a prospective randomized controlled trial. Knee Surgery, Sports Traumatology, Arthroscopy 2013;21(11):2611-7. - PubMed
Lee 2017 {published data only}
    1. Lee SY, Chong S, Balasubramanian D, Na YG, Kim TK. What is the ideal route of administration of tranexamic acid in TKA? A randomized controlled trial. Clinical Orthopaedics and Related Research 2017;475(8):1987-96. - PMC - PubMed
Lee 2017a {published data only}
    1. Lee QJ, Ching WY, Wong YC. Blood sparing efficacy of oral tranexamic acid in primary total knee arthroplasty: a randomized controlled trial. Knee Surgery & Related Research 2017;29(1):57-62. - PMC - PubMed
Lei 2020a {published data only}
    1. ChiCTR2000029720. Effects of preemptive antifibrinolysis of tranexamic acid in total knee arthroplasty under enhanced recovery after surgery. www.chictr.org.cn/showproj.aspx?proj=49163 (first received 10 February 2020).
    1. Effects of preemptive antifibrinolysis of tranexamic acid in total knee arthroplasty under enhanced recovery after surgery. www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR2000029720.
    1. Lei Y, Liu J, Liang X, Hu N, Pei F, Huang W. Effectiveness of preemptive antifibrinolysis with tranexamic acid in rheumatoid arthritis patients undergoing total knee arthroplasty: a study protocol for a randomized controlled trial. BMC Musculoskeletal Disorders 2020;21(1):465. - PMC - PubMed
Liebelt 2013 {published data only}
    1. Liebelt DA, Levy BJ, Kadimcher PK, Krystal JD, Li R, Lall A, et al. Effects of intraoperative use of the topical hemostatic matrix agent, Floseal, in primary unilateral total knee arthroplasty. Current Orthopaedic Practice 2013;24(5):509-12.
Lin 2015 {published data only}
    1. Lin SY, Chen CH, Fu YC, Huang PJ, Chang JK, Huang HT. The efficacy of combined use of intraarticular and intravenous tranexamic acid on reducing blood loss and transfusion rate in total knee arthroplasty. Journal of Arthroplasty 2015;30(5):776-80. - PubMed
Li‐Qing 2018 {published data only}
    1. Li-Qing Z, Kai-Bin W, Ben-Ke Z, Qiang W, Chun-Pu L. Rational application of tranexamic acid and drainage tube in total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2018;22(27):4282-7.
Liu 2018 {published data only}
    1. Liu W, Yang C, Huang X, Liu R. Tranexamic acid reduces occult blood loss, blood transfusion, and improves recovery of knee function after total knee arthroplasty: a comparative study. In: Journal of Knee Surgery. 2017. - PubMed
    1. Liu W, Yang C, Huang X, Liu R. Tranexamic acid reduces occult blood loss, blood transfusion, and improves recovery of knee function after total knee arthroplasty: a comparative study. Journal of Knee Surgery 2018;31(3):239-46. - PubMed
Liu 2021 {published data only}
    1. Liu JL, Yin L, Zhang Y, Wang HT, Li ZY, Xia PG, et al. Effects of intravenous tranexamic acid combined with periarticular multipoint injection of tranexamic acid cocktail on blood loss and pain after total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2021;25(18):2833-9.
Lopez‐Hualda 2018 {published data only}
    1. Lopez-Hualda A, Dauder-Gallego C, Ferreno-Marquez D, Martinez-Martin J. Efficacy and safety of topical tranexamic acid in knee arthroplasty. Medicina Clínica 2018;151(11):431-4. - PubMed
Luo 2018 {published data only}
    1. Luo ZY, Wang D, Meng WK, Wang HY, Pan H, Pei FX, et al. Oral tranexamic acid is equivalent to topical tranexamic acid without drainage in primary total hip arthroplasty: a double-blind randomized clinical trial. Thrombosis Research 2018;167:1-5. - PubMed
Ma 2014 {published data only}
    1. Ma JH, Sun W, Gao FQ, Wang YT, Li ZR. Blood loss and limb circumference changes in patients undergoing unilateral total knee arthroplasty after intra-articular injection of tranexamic acid: a randomized controlled trial.. Journal of Clinical Rehabilitative Tissue Engineering Research 2014;18(35):5577-82.
MacGillivray 2011 {published data only}
    1. MacGillivray RG, Tarabichi SB, Hawari MF, Raoof NT. Tranexamic acid to reduce blood loss after bilateral total knee arthroplasty: a prospective, randomized double blind study. Journal of Arthroplasty 2011;26(1):24-8. - PubMed
Malhotra 2011 {published data only}
    1. Malhotra R, Kumar V, Garg B. The use of tranexamic acid to reduce blood loss in primary cementless total hip arthroplasty. European Journal of Orthopaedic Surgery & Traumatology 2011;21(2):101-4.
Maniar 2012 {published data only}
    1. Maniar RN, Kumar G, Singhi T, Nayak RM, Maniar PR. Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients. Clinical Orthopaedics and Related Research 2012;470(9):2605-12. - PMC - PubMed
May 2016 {published data only}
    1. May JH, Rieser GR, Williams CG, Markert RJ, Bauman RD, Lawless MW. The assessment of blood loss during total knee arthroplasty when comparing intravenous vs intracapsular administration of tranexamic acid. Journal of Arthroplasty 2016;31(11):2452-7. - PubMed
McDonald 2017 {published data only}
    1. McDonald CK, Feeley I, Sheehan E. The effect of oral transexamic acid on postoperative knee arthroplasty patients; a prospective randomised control trial. Irish Journal of Medical Science 2017;186((2 Suppl 1)):S117.
McDonald 2022 {published data only}
    1. EUCTR-2017-002403-96-IE. The addition of oral tranexamic acid to knee arthroplasty patients does not further improve blood loss: a double blinded randomized control trial. www.clinicaltrialsregister.eu/ctr-search/search?query=2017-002403-96. - PubMed
    1. McDonald C, Feeley I, Flynn S, Farrell A, Kelly M, Sheehan E. The addition of oral Tranexamic acid to knee arthroplasty patients does not further improve blood loss: a double blinded randomized control trial. Acta Orthopaedica Belgica 2022;88(2):335-41. [DOI: 10.52628/88.2.8383.] - DOI - PubMed
Mehta 2019 {published data only}
    1. Mehta N, Goel N, Goyal A, Joshi D, Chaudhary D. A prospective comparative study between intravenous and intraarticular tranexamic acid administration in decreasing the perioperative blood loss in total knee arthroplasty. Journal of Arthroscopy and Joint Surgery 2019;6(1):70-3.
Min 2015 {published data only}
    1. Min P, Peng YX, Hu JH, Gu ZC. Efficacy and safety of tranexamic acid on blood loss after unilateral total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2015;19(17):2655-60.
Moo 2017 {published data only}
    1. Moo IH, Chen JYQ, Pagkaliwaga EH, Tan SW, Poon KB. Bone wax is effective in reducing blood loss after total knee arthroplasty. In: Journal of Arthroplasty. 2016. - PubMed
    1. Moo IH, Chen JYQ, Pagkaliwaga EH, Tan SW, Poon KB. Bone wax is effective in reducing blood loss after total knee arthroplasty. Journal of Arthroplasty 2017;32(5):1483-7. - PubMed
Na 2016 {published data only}
    1. Na HS, Shin HJ, Lee YJ, Kim JH, Koo KH, Do SH. The effect of tranexamic acid on blood coagulation in total hip replacement arthroplasty: rotational thromboelastographic (rotem) analysis. Anaesthesia 2016;71(1):67-75. - PubMed
Nambiar 2019 {published data only}
    1. Nambiar HR, Kamath SS. Comparison of efficacy of tranexamic acid 10 mg/kg and 15 mg/kg in reducing bleeding and transfusions in total knee arthroplasty. Asian Journal of Pharmaceutical and Clinical Research 2019;12(3):535-8.
NCT00983112 {published data only}
    1. EUCTR2009-010802-12-FR. Etude de l’impact d’une colle biologique sur le saignement péri-opératoire lors d’une chirurgie pour pose de Prothèse Totale de Genou (PTG). Etude EVICEL®. - Evicel study. trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2009-010802-12-FR 2009.
    1. NCT00983112. Evicel study on the peri-operative bleeding in total knee prothesis surgery. clinicaltrials.gov/ct2/show/NCT00983112 2009.
NCT01260818 {published data only}
    1. NCT01260818. Topical application of tranexamic acid reduces postoperative blood loss in total hip arthroplasty. www.clinicaltrials.gov/ct2/show/NCT01260818 2010.
NCT01391182 {published data only}
    1. NCT01391182. Epsilon aminocaproic acid (EACA) for the reduction of blood loss in total hip arthroplasty (THA). clinicaltrials.gov/ct2/show/NCT01391182 2011.
NCT01527968 {published data only}
    1. NCT01527968. Epsilon aminocaproic acid vs. tranexamic acid vs. placebo for prevention of blood loss in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT01527968 2012.
NCT02056444 {published data only}
    1. NCT02056444. Efficacy of intravenous versus topical tranexamic acid in primary total hip arthroplasty. clinicaltrials.gov/ct2/show/NCT02056444 2014.
NCT02117128 {published data only}
    1. NCT02117128. The efficacy and safety of using tranexamic acid by different means to reduce blood loss during total knee replacement. clinicaltrials.gov/ct2/show/NCT02117128 2014.
NCT02286973 {published data only}
    1. NCT02286973. Combined administration of intravenous and topical tranexamic acid in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT02286973 2014.
NCT02438566 {published data only}
    1. NCT02438566. Non-inferiority trial of oral tranexamic acid vs. intravenous tranexamic acid in joint replacement surgery. clinicaltrials.gov/ct2/show/NCT02438566 2015.
NCT02587845 {published data only}
    1. NCT02587845. Use of transexamic acid in hip replacement. clinicaltrials.gov/ct2/show/NCT02587845 2015.
NCT02938962 {published data only}
    1. NCT02938962. Intravenous vs. topical tranexamic acid in revision THA (VITALITY-X). clinicaltrials.gov/ct2/show/NCT02938962 2016.
NCT03109652 {published data only}
    1. NCT03109652. Serial use of intravenous and oral tranexamic acid in primary total knee arthroplasty patients. clinicaltrials.gov/ct2/show/NCT03109652.
NCT03310060 {published data only}
    1. NCT03310060. Reducing blood loss using Tisseel in TKA. clinicaltrials.gov/ct2/show/NCT03310060 2017.
NCT03386656 {published data only}
    1. NCT03386656. Efficacy and safety of topical application of tranexamic acid for saving blood losses in patients subjected to prosthetic knee surgery. clinicaltrials.gov/ct2/show/NCT03386656 2017.
NCT03822793 {published data only}
    1. NCT03822793. A dose-response study of tranexamic acid in total hip arthroplasty. clinicaltrials.gov/ct2/show/NCT03822793 2019.
NCT0393407 {published data only}
    1. NCT03934047. Visual field infiltration of tranexamic acid reduced the blood loss in total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT03934047 2019.
Ni 2016 {published data only}
    1. Ni JR, Wang LX, Chen XJ. Comparison of different modes of using tranexamic acid administration on reducing hidden blood loss in total hip arthroplasty. China Journal of Orthopaedics and Traumatology 2016;29(8):713-7. - PubMed
Notarnicola 2012 {published data only}
    1. Notarnicola A, Moretti L, Martucci A, Spinarelli A, Tafuri S, Pesce V, et al. Comparative efficacy of different doses of fibrin sealant to reduce bleeding after total knee arthroplasty. Blood Coagulation & Fibrinolysis 2012;23(4):278-84. - PubMed
Obaidur 2014 {published data only}
    1. Obaid ur R, Hafeez S, Amin MS, Syed HM, Shah WA, Talha M, et al. Preventing the preventable: role of transamine in total knee arthroplasty. Journal of Pakistan Medical Association 2014;64((12 Suppl 2)):S44-8. - PubMed
Oztas 2015 {published data only}
    1. Oztas S, Ozturk A, Akalin Y, Sahin N, Ozkan Y, Otuzbir A. The effect of local and systemic application of tranexamic acid on the amount of blood loss and allogeneic blood transfusion after total knee replacement. Acta Orthopaedica Belgica 2015;81(4):698-707. - PubMed
Pan 2019 {published data only}
    1. Pan DQ, Chen LL, Sun B, Yu Z, Ge JB, Miao MF. Effect of tranexamic acid combined flexion position of hip and knee on perioperative bleeding following unilateral total knee arthroplasty. Zhongguo Gushang 2019;32(8):759-64. - PubMed
Patel 2014 {published data only}
    1. Patel JN, Spanyer JM, Smith LS, Huang J, Yakkanti MR, Malkani AL. Comparison of intravenous versus topical tranexamic acid in total knee arthroplasty: a prospective randomized study. Journal of Arthroplasty 2014;29(8):1528-31. - PubMed
Patni 2012 {published data only}
    1. Patni P, Khanna R, Dewangan S, Mody B. Role of tranexamic acid in reducing blood loss in total knee arthroplasty prosceptive, randomized, double-blinded study on perfectly matched group. Journal of Orthopaedics 2012;9(1):e13.
Piolanti 2018 {published data only}
    1. Piolanti N, Del Chiaro A, Matassi F, Graceffa A, Nistri L Marcucci M. Clinical and instrumental evaluation of two different regimens of tranexamic acid in total hip arthroplasty: a single-centre, prospective, randomized study with 80 patients. European Journal of Orthopaedic Surgery & Traumatology 2018;28:233-7. - PubMed
Prabhu 2015 {published data only}
    1. Prabhu T, Deepak M, Harish R, Narasimhan V. Efficacy of tranexamic acid in conservation of blood loss in total knee arthroplasty patients. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2015;6(2):987-92.
Prakash 2018 {published data only}
    1. Prakash J, Seon JK, Park YJ, Jin C, Song EK. A randomized control trial to evaluate the effectiveness of intravenous, intra-articular and topical wash regimes of tranexamic acid in primary total knee arthroplasty. Journal of Orthopaedic Surgery 2017;25(1):2309499017693529. - PubMed
    1. Prakash J, Seon JK, Song EK, Lee DH, Yang HY, Jin C. Is combined administration of tranexamic acid better than both intravenous and topical regimes for total loss, hidden loss and post-operative swelling? A randomized control trial. Indian Journal of Orthopaedics 2018;52(2):117-23. - PMC - PubMed
    1. Song EK, Seon JK, Prakash J, Seol YJ, Park YJ, Jin C. Combined administration of iv and topical tranexamic acid is not superior to either individually in primary navigated TKA. The Journal of Arthroplasty 2017;32(1):37-42. - PubMed
Raviraj 2012 {published data only}
    1. Raviraj A, Anand A, Chakravarthy M, Kumarswamy S, Prabhu A, Pai S. Tranexamic acid reduces blood loss in simultaneous bilateral total knee arthroplasty: a randomized control trial. European Journal of Orthopaedic Surgery & Traumatology volume 2012;22(5):381-6.
Rizzo 2020 {published data only}
    1. Rizzo M, Russo AP, Guarino A, Izzo A, Mariconda M. A comparative study of combined intravenous and topical administration of tranexamic acid with topical tranexamic acid alone for blood loss reduction after primary uncemented total hip arthroplasty. Journal of Biological Regulators & Homeostatic Agents. Advances in Musculoskeletal Diseases and Infections - SOTIMI 2020;34(3 Suppl 2):16. - PubMed
Sarzaeem 2014 {published data only}
    1. Sarzaeem MM, Razi M, Kazemian G, Moghaddam ME, Rasi AM, Karimi M. Comparing efficacy of three methods of tranexamic acid administration in reducing hemoglobin drop following total knee arthroplasty. Journal of Arthroplasty 2014;29(8):1521-4. - PubMed
Seo 2013 {published data only}
    1. Seo JG, Moon YW, Park SH, Kim SM, Ko KR. The comparative efficacies of intra-articular and iv tranexamic acid for reducing blood loss during total knee arthroplasty. Knee Surgery, Sports Traumatology, Arthroscopy 2013;21(8):1869-74. - PubMed
Shen 2015 {published data only}
    1. Shen PF, Hou WL, Chen JB, Wang B, Qu YX. Effectiveness and safety of tranexamic acid for total knee arthroplasty: a prospective randomized controlled trial. Medical Science Monitor 2015;21:576-81. - PMC - PubMed
Shinde 2015 {published data only}
    1. Shinde A, Sobti A, Maniar S, Mishra A, Gite R, Shetty V. Tranexamic acid reduces blood loss and need of blood transfusion in total knee arthroplasty: a prospective, randomized, double-blind study in Indian population. Asian Journal of Transfusion Science 2015;9(2):168-72. - PMC - PubMed
Singh Sidhu 2021 {published data only}
    1. Singh Sidhu GA, Marya SKS, Singh C, Kacker S, Singh S. Efficacy of topical versus intravenous tranexamic acid in bilateral total knee arthroplasty. Journal of Arthroscopy and Joint Surgery 2021;8(4):346-9.
Soni  2014 {published data only}
    1. Soni A, Saini R, Gulati A, Paul R, Bhatty S, Rajoli SR. Comparison between intravenous and intra-articular regimens of tranexamic acid in reducing blood loss during total knee arthroplasty. Journal of Arthroplasty 2014;29(8):1525-7. - PubMed
Specchiulli 2011 {published data only}
    1. Specchiulli F, Rendina M, Berardi M. Reduction of blood loss using tranexamic acid in total knee and hip arthroplasties. In: Journal of Orthopaedics and Traumatology. Vol. 12. 2011:S87.
Sun 2016 {published data only}
    1. Sun SW, Yang L, Xie SA, Wang J, Xu RB. Combined use of intraarticular and intravenous tranexamic acid in total hip arthroplasty. Chinese Journal of Tissue Engineering Research 2016;20(48):7149-55.
Sun 2017 {published data only}
    1. Sun Q, Yu X, Nie X, Gong J, Cai M. The efficacy comparison of tranexamic acid for reducing blood loss in total knee arthroplasty at different dosage time. Journal of Arthroplasty 2017;32(1):33-6. - PubMed
    1. Sun Q, Yu X, Wu J, Ge W, Cai M, Li S. Efficacy of a single dose and an additional dose of tranexamic acid in reduction of blood loss in total knee arthroplasty. Journal of Arthroplasty 2017;32(7):2108-12. - PubMed
Taheriazam 2018 {published data only}
    1. Taheriazam A, Safdari F, Sahebalzamani MA. Local tranexamic acid plus diluted epinephrine vs. intravenous tranexamic acid for reducing bleeding in revision total hip arthroplasty. HIP International 2016;26(Suppl 2):S45.
    1. Taheriazam A, Safdari F. Local tranexamic acid plus diluted epinephrine vs. Intravenous tranexamic acid for reducing bleeding in revision total hip arthroplasty. HIP International 2018;28(Suppl 1):140.
    1. Taheriazam A, Safdari F. Using tranexamic acid to decrease postoperative hemorrhage: local versus intravenous administration. HIP International 2015;1:S90.
    1. Taheriazam A, Safdari F. Using tranexamic acid to decrease postoperative hemorrhage: local versus intravenous administration. HIP International 2016;26(Suppl 2):S41.
Taheriazam 2019 {published data only}
    1. Taheriazam A, Safdari F. Local tranexamic acid plus diluted epinephrine vs. intravenous tranexamic acid for reducing bleeding in revision total hip arthroplasty. In: SICOT 40th Orthopaedic World Congress. 2019.
Tang 2019 {published data only}
    1. Tang Y, Wen Y, Li W, Li H, Yang Y, Liu Y. The efficacy and safety of multiple doses of oral tranexamic acid on blood loss, inflammatory and fibrinolysis response following total knee arthroplasty: a randomized controlled trial. International Journal of Surgery 2019;65:45-51. - PubMed
Triyudanto 2016 {published data only}
    1. Triyudanto AN, Lubis AMT. The effects of intra-articular tranexamic acid given intraoperatively and intravenous tranexamic acid given preoperatively on post surgical bleeding and transfusion rate post total knee arthroplasty. Medical Journal of Indonesia 2016;25(4):234-9.
Tzatzairis 2019 {published data only}
    1. Tzatzairis T, Drosos GI, Vogiatzaki T, Tilkeridis K, Ververidis A, Kazakos K. Multiple intravenous tranexamic acid doses in total knee arthroplasty without tourniquet: a randomized controlled study. Archives of Orthopaedic and Trauma Surgery 2019;139(6):859-68. - PubMed
Ugurlu 2017 {published data only}
    1. Ugurlu M, Aksekili MA, Caglar C, Yuksel K, Sahin E, Akyol M. Effect of topical and intravenously applied tranexamic acid compared to control group on bleeding in primary unilateral total knee arthroplasty. Journal of Knee Surgery 2017;30(2):152-7. - PubMed
UMIN000029797 {published data only}
    1. UMIN000029797. Intravenous versus combined intravenous and intra-articular tranexamic acid for simultaneous bilateral total hip arthroplasty: randomized controlled trial. center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_his_list.cgi?recptno=R000033781 2017.
Vandesande 2015 {published data only}
    1. Vandesande W, Haenen F. Topical use of tranexamic acid in total hip arthroplasty. A prospective randomized controlled trial. HIP International 2015;25(Suppl 1):S34.
Volquind 2016 {published data only}
    1. Volquind D, Zardo RA, Winkler BC, Londero BB, Zanelatto N, Leichtweis GP. Use of tranexamic acid in primary total knee replacement: effects on perioperative blood loss. Brazilian Journal of Anesthesiology 2016;66(3):254-8. - PubMed
Wang 2015 {published data only}
    1. Wang R, Tian SQ, Ha CZ, Song RX, Sun K. Efficacy and safety of tranexamic acid on reducing blood loss in bilateral total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2015;19(22):3451-6.
Wang 2015a {published data only}
    1. Wang G, Wang D, Wang B, Lin Y, Sun S. Efficacy and safety evaluation of intra-articular injection of tranexamic acid in total knee arthroplasty operation with temporarily drainage close. International Journal of Clinical and Experimental Medicine 2015;8(8):14328-34. - PMC - PubMed
Wang 2015b {published data only}
    1. Wang CG, Sun ZH, Liu J, Cao JG, Li ZJ. Safety and efficacy of intra-articular tranexamic acid injection without drainage on blood loss in total knee arthroplasty: a randomized clinical trial. International Journal of Surgery 2015;20:1-7. - PubMed
Wang 2016 {published data only}
    1. Wang C, Kang P, Ma J, Yue C, Xie J, Pei F. Single-dose tranexamic acid for reducing bleeding and transfusions in total hip arthroplasty: a double-blind, randomized controlled trial of different doses. Thrombosis Research 2016;141:119-23. - PubMed
Wang 2017 {published data only}
    1. Wang J, Wang Q, Zhang X, Wang Q. Intra-articular application is more effective than intravenous application of tranexamic acid in total knee arthroplasty: a prospective randomized controlled trial. Journal of Arthroplasty 2017;32(11):3385-9. - PubMed
Wei 2014 {published data only}
    1. Wei W, Wei B. Comparison of topical and intravenous tranexamic acid on blood loss and transfusion rates in total hip arthroplasty. Journal of Arthroplasty 2014;29(11):2113-6. - PubMed
Wu 2016a {published data only}
    1. Wu YG, Zeng Y, Yang TM, Si HB, Cao F, Shen B. The efficacy and safety of combination of intravenous and topical tranexamic acid in revision hip arthroplasty: a randomized, controlled trial. Journal of Arthroplasty 2016;31(11):2548-53. - PubMed
Wu 2018a {published data only}
    1. Wu J, Li G, Chen Y, Deng J, Zhang C. Comparison of combined intravenous and topical use of tranexamic acid with different dosage in primary total knee arthroplasty. Chinese Journal of Rehabilitation and Reconstructive Surgery 2018;32(11):1397-401. - PMC - PubMed
Wu 2019 {published data only}
    1. Wu XY, Zhang GR, Liu T, Zhou CH. Intravenous and intraarticular tranexamic acid can reduce blood loss and inflammatory response during cemented posterior cruciate ligament-retaining unilateral total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2019;23(36):5753-9.
Wu 2019a {published data only}
    1. Wu J, Feng S, Chen X, Lv Z, Qu Z, Chen H, et al. Intra-articular injection of tranexamic acid on perioperative blood loss during unicompartmental knee arthroplasty. Medical Science Monitor 2019;25:5068-74. - PMC - PubMed
Wu 2020 {published data only}
    1. Wu XF, Yin ZF, Sun BF, Dong F, Qian PK, Zhang JB, et al. Analysis of hemostatic effect of intra-articular injection of tranexamic acid after minimally invasive unicompartmental knee arthroplasty. Zhongguo Gushang 2020;33(11):1068-71. - PubMed
Wu 2020a {published data only}
    1. Wu J, Zhou YQ, Deng JH, Han YG, Zhu YC, Qian QR. Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: a prospective, randomized and controlled study. Annals of Translational Medicine 2020;8(21):1353. - PMC - PubMed
Xiaofei 2020 {published data only}
    1. Xiaofei L, Xuan W, Jinliang W. Effect of tranexamic acid on ischemia-reperfusion injury caused by application of tourniquet in the surgery of total knee arthroplasty. Orthopaedic Journal of Sports Medicine. Conference: DKG International Knee Day 2020;8(9 Suppl 7).
Xie 2016a {published data only}
    1. Xie J, Ma J, Yue C, Kang P, Pei F. Combined use of intravenous and topical tranexamic acid following cementless total hip arthroplasty: a randomised clinical trial. HIP International 2016;26(1):36-42. - PubMed
Xu 2016 {published data only}
    1. Xu J, Ha CZ, Tian SQ, Wang YH, Liu NN, Sun K. Intra-articular and intravenous injection of tranexamic acid effectively reduces blood loss after total knee arthroplasty. Chinese Journal of Tissue Engineering Research 2016;20(17):2437-42.
Xu 2019b {published data only}
    1. Xu X, Jiang J, Liu W, Li X, Lu H. Application of thromboelastography to evaluate the effect of different routes administration of tranexamic acid on coagulation function in total hip arthroplasty. Journal of Orthopaedic Surgery 2019;14(1):430. - PMC - PubMed
Yang 2015 {published data only}
    1. Yang Y, Lv YM, Ding PJ, Li J, Ying-Ze Z. The reduction in blood loss with intra-articular injection of tranexamic acid in unilateral total knee arthroplasty without operative drains: a randomized controlled trial. European Journal of Orthopaedic Surgery & Traumatology 2015;25(1):135-9. - PubMed
Ye 2019 {published data only}
    1. Ye X, Chen Y, Lin K, Zheng Y, Jiang C. Clinical study of the optimal dose of intravenous tranexamic acid guided by thrombelastogram during the perioperative period of total knee arthroplasty. International Journal of Clinical and Experimental Medicine 2019;12(6):6989-98.
Yue 2014 {published data only}
    1. Yue C, Kang P, Yang P, Xie J, Pei F. Topical application of tranexamic acid in primary total hip arthroplasty: a randomized double-blind controlled trial. Journal of Arthroplasty 2014;29(12):2452-6. - PubMed
Zeng 2016 {published data only}
    1. Zeng B, Liu G, He ZS, Zheng LJ, Jing FB, Lv H. Effects of intraarticular tranexamic acid injection combined with 3-hour drainage tube occlusion postoperatively on blood loss in unicompartmental knee arthroplasty. Chinese Journal of Tissue Engineering Research 2016;20(22):3197-204.
Zhang 2015 {published data only}
    1. Zhang CH, Liu Y, Zhao JN, Meng J, Yuan T, Ni-Rong B. Intravenous drip and topical application using tranexamic acid decrease hidden blood loss after total hip arthroplasty. Chinese Journal of Tissue Engineering Research 2015;19(44):7071-6.
Zhang 2016 {published data only}
    1. Zhang Y, Zhang L, Ma X, Jia Y, Wang H, Zhu Y, et al. What is the optimal approach for tranexamic acid application in patients with unilateral total hip arthroplasty? Der Orthopäde 2016;45(7):616-21. - PubMed
Zhang 2018 {published data only}
    1. Zhang F. The effect of intra-articular tranexamic acid injection on unicompartmental knee arthroplasty patients' blood loss volume in perioperative period. Osteoporosis International 2018;29((1 Suppl 1)):S208.
Zhang 2019 {published data only}
    1. Zhang YM, Yang B, Sun XD, Zhang Z. Combined intravenous and intra-articular tranexamic acid administration in total knee arthroplasty for preventing blood loss and hyperfibrinolysis: a randomized controlled trial. Medicine 2019;98(7):e14458. - PMC - PubMed
Zhang 2019a {published data only}
    1. Zhang S, Wang C, Shi L, Xue Q. Multi-route applications of tranexamic acid to reduce blood loss after total knee arthroplasty: a randomized controlled trial. Medicine 2019;98(30):e16570. - PMC - PubMed
Zhang 2020 {published data only}
    1. Zhang Y, Qian XJ, Dong YP, Ji WF, Shen J. Efficacy and safety of tranexamic acid in total hip arthroplasty via direct anterior approach. Zhongguo Gushang 2020;33(11):1037-41. - PubMed
Zhang 2020a {published data only}
    1. Zhang X, Ma D, Wen L, Pan J. Better treatment values in local application of tranexamic acid (TXA) than intravenous application with the same dose in total hip arthroplasty. Advances in Therapy 2020;37(10):4346-55. - PubMed
Zhang 2020b {published data only}
    1. Zhang XC, Sun MJ, Pan S, Rui M, Zhao FC, Zha GC, et al. Intravenous administration of tranexamic acid in total hip arthroplasty does not change the blood coagulopathy: a prospective thrombelastography analysis. Journal of Orthopaedic Surgery 2020;28(3):2309499020959516. - PubMed
Zhaohui 2014 {published data only}
    1. Zhaohui L, Wanshou G, Qidong Z, Guangduo Z. Topical hemostatic procedures control blood loss in bilateral cemented single-stage total knee arthroplasty. Journal of Orthopaedic Science 2014;19(6):948-53. - PubMed

References to ongoing studies

ChiCTR1800016960 {published data only}
    1. ChiCTR1800016960. Multiple boluses of oral tranexamic acid to reduce hidden blood loss after primary medial unicompartmental knee arthroplasty without tourniquet: a randomized clinical trial. www.chictr.org.cn/showproj.aspx?proj=28842 2018.
ChiCTR1800017038 {published data only}
    1. ChiCTR1800017038. Multiple boluses of oral tranexamic acid to reduce hidden blood loss after primary knee arthroplasty: a randomized clinical trial. www.chictr.org.cn/showproj.aspx?proj=28966 2018.
ChiCTR1800017094 {published data only}
    1. ChiCTR1800017094. Multiple boluses of oral and topical tranexamic acid to reduce hidden blood loss after primary hip arthroplasty: a randomized clinical trial. www.chictr.org.cn/showproj.aspx?proj=29083 2018.
ChiCTR1800017095 {published data only}
    1. ChiCTR1800017095. Multiple boluses of oral and iv tranexamic acid to reduce hidden blood loss after primary total hip arthroplasty: a randomized clinical trial. www.chictr.org.cn/showproj.aspx?proj=29084 2018.
ChiCTR1800018100 {published data only}
    1. ChiCTR1800018100. Multiple boluses of oral tranexamic acid (TXA) to reduce hidden blood loss after primary total hip arthroplasty using a direct anterior approach: a randomized clinical trial. www.chictr.org.cn/showproj.aspx?proj=30586 2018.
ChiCTR1800018751 {published data only}
    1. ChiCTR1800018751. Assessment of safety and effect on tranexamic acid in total knee arthroplasty. www.chictr.org.cn/showproj.aspx?proj=31701 2018.
ChiCTR1800019261 {published data only}
    1. ChiCTR1800019261. The blood sparing, anti-fibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty: a randomized controlled trial. www.chictr.org.cn/showproj.aspx?proj=32410 2018.
ChiCTR1900020498 {published data only}
    1. ChiCTR1900020498. Efficacy of tranexamic acid combined with carbazochrome sodium sulfonate on blood loss in primary total hip arthroplasty using a direct anterior approach: a prospective randomized controlled trial. www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR1900020498.
ChiCTR2000035271 {published data only}
    1. ChiCTR2000035271. Analgesic effects of tranexamic acid: intra-articular injection versus not——a randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=40681 2020.
ChiCTR2000039368 {published data only}
    1. ChiCTR2000039368. Efficacy and safety of postoperative intravenous tranexamic acid in total knee arthroplasty: a prospective randomized controlled study. www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR2000039368. - PMC - PubMed
ChiCTR2100045474 {published data only}
    1. Effect of tranexamic acid on blood protection in patients undergoing total hip arthroplasty. www.chictr.org.cn/showprojen.aspx?proj=125218.
ChiCTR‐INR‐16008762 {published data only}
    1. ChiCTR-INR-16008762. Is tourniquet really necessary when multiple uses of intravenous and topical tranexamic acid are applied in primary total knee arthroplasty? A prospective randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=14780 2016.
ChiCTR‐INR‐16010030 {published data only}
    1. ChiCTR-INR-16010030. Optimized cocktail therapy during operation in ERAS total hip and knee arthroplasty: a prospective randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=17061 2016.
ChiCTR‐INR‐17013711 {published data only}
    1. ChiCTR-INR-17013711. The clinical effect of multiple high-dose intravenous tranexamic acid in peri-operative period of total hip/knee arthroplasty under the management of enhanced recovery after surgery: a prospective, randomized, controlled study. www.chictr.org.cn/showprojen.aspx?proj=23448 2017.
ChiCTR‐IPC‐14005579 {published data only}
    1. ChiCTR-IPC-14005579. Intravenous versus intravenous combined with topical administration of tranexamic acid in primary total knee arthroplasty: a randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=9971 2104.
ChiCTR‐IPR‐16008175 {published data only}
    1. ChiCTR-IPR-16008175. The cocktail therapy control the blood loss and pain after total hip arthroplasty: a randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=13151 2016.
ChiCTR‐IPR‐16008176 {published data only}
    1. ChiCTR-IPR-16008176. The cocktail therapy control the blood loss and pain after total knee arthroplasty: a randomized controlled trial. www.chictr.org.cn/showprojen.aspx?proj=13159 2016.
CTRI/2022/03/041001 {published data only}
    1. CTRI/2022/03/041001. Study on the effectiveness of tranexamic acid(drug) in reducing blood loss during hip surgeries. trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2022/03/041001.
EUCTR‐2008‐007110‐29‐FR {published data only}
    1. EUCTR-2008-007110-29. An international randomised, double-blind, placebo-controlled study to assess the efficacy and safety of 2 dosing regimens of FIBRINOGENE T1 in the treatment of peri-operative bleeding associated with revision total hip arthroplasty. www.clinicaltrialsregister.eu/ctr-search/trial/2008-007110-29/FR 2009.
EUCTR‐2016‐000071‐24‐ES {published data only}
    1. EUCTR-2016-000071-24-ES. Time of administration of tranexamic acid to prevent bleeding in total knee arthroplasty. www.clinicaltrialsregister.eu/ctr-search/trial/2016-000071-24/ES 2016.
EUCTR‐2018‐003537‐15 {published data only}
    1. EUCTR-2018-003537-15-AT. Different dosing of tranexamic acid in patients undergoing elective total hip or knee arthroplasty. A randomized, controlled, double-blinded clinical trial.. www.clinicaltrialsregister.eu/ctr-search/trial/2018-003537-15/AT (first received 2019).
EUCTR‐2020‐003321‐32‐DK {published data only}
    1. EUCTR-2020-003321-32-DK. Does tranexamic acid, a medicine used in treating and preventing bleeding problems, reduce the blood loos when it is injected directly into the hip joint after insertion of a total hip prosthesis. trialsearch.who.int/?TrialID=EUCTR2020-003321-32-DK 2020.
EUCTR‐2020‐004167‐29‐BE {published data only}
    1. EUCTR-2020-004167-29-BE. Evaluation of equivalence between oral versus intravenous administration of tranexamic acid in total hip replacement surgery. www.clinicaltrialsregister.eu/ctr-search/trial/2020-004167-29/BE (first received 8 February 2021).
NCT03623789 {published data only}
    1. NCT03623789. Blood-saving effect of combined intravenous tranexamic acid with topical Floseal® application total hip arthroplasty. clinicaltrials.gov/ct2/show/NCT03623789 (first received 2018).
NCT03897621 {published data only}
    1. NCT03897621. The effect of tranexamic acid on blood coagulation in total hip arthroplasty surgery. clinicaltrials.gov/ct2/show/NCT03897621 (first received 2019).
NCT04691362 {published data only}
    1. NCT04691362. Noninferiority oral tranexamic acid vs intravenous administration in total hip arthroplasty. www.clinicaltrials.gov/ct2/show/NCT04691362 (first received 2020).
NCT04992052 {published data only}
    1. NCT04992052. Bone wax use for hemostasis during primary unilateral total knee arthroplasty. clinicaltrials.gov/ct2/show/NCT04992052 (first received 2021).
NCT05099276 {published data only}
    1. NCT05099276. Extended postoperative oral tranexamic acid in knee replacement. clinicaltrials.gov/ct2/show/record/NCT05099276 (first received 2021).
UMIN000047607 {published data only}
    1. Randomized control trial for suppression of perioperative bleeding byetween tranexamic acid and surge cell. center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054288.
Yang 2021 {published data only}
    1. ChiCTR2000030624. A prospective, randomized, controlled study on the efficacy and safety of different strategies of tranexamic acid in patients undergoing total knee arthroplasty. www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR2000030624 (first received 2020).
    1. Yang Y, Wang Z, Wang F, Zhao X, Yang K, He J, et al. Prospective, randomised, controlled study on the efficacy and safety of different strategies of tranexamic acid with total blood loss, blood transfusion rate and thrombogenic biomarkers in total knee arthroplasty: study protocol. BMJ Open 2021;11(2):e038399. - PMC - PubMed

Additional references

Aleman 2014
    1. Aleman MM, Byrnes JR, Wang J-G, Tran R, Lam WA, Di Paola J, et al. Factor XIII activity mediates red blood cell retention in venous thrombi. Journal of Clinical Investigation 2014;124(8):3590-600. - PMC - PubMed
Baird 2015
    1. Baird EO, McAnany SJ, Lu Y, Overley SC, Qureshi SA. Hemostatic agents in spine surgery: a critical analysis review. JBJS Reviews 2015;3(1):1-8. - PubMed
Basques 2015
    1. Basques B, Toy J, Bohl D, Golinvaux N, Grauer J. General compared with spinal anesthesia for total hip arthroplasty. Journal of Bone and Joint Surgery 2015;97(6):455-61. - PMC - PubMed
BNF 2022
    1. Joint Formulary Committee. British National Formulary. 76 edition. London (UK): BMJ Group and Pharmaceutical Press, 2022.
Broughton 2021
    1. Broughton SL, Wilkinson J, Bero L. When beauty is but skin deep: dealing with problematic studies in systematic reviews (Editorial). Cochrane Database of Systematic Reviews 2021, Issue 6. [DOI: 10.1002/14651858.ED000152] - DOI - PMC - PubMed
Bucher 1997
    1. Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. Journal of Clinical Epidemiology 1997;50(6):683-91. - PubMed
BUGSnet
    1. Béliveau A, Boyne DJ, Slater J, Brenner D, Arora P. BUGSnet: an R package to facilitate the conduct and reporting of Bayesian network meta-analyses. BMC Medical Research Methodology 2019;19(1):196. [DOI: 10.1186/s12874-019-0829-2] - DOI - PMC - PubMed
Caldwell 2005
    1. Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 2005;331(7521):897-900. - PMC - PubMed
Carless 2003
    1. Carless PA, Henry DA, Anthony DM. Fibrin sealant use for minimising peri‐operative allogeneic blood transfusion. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No: CD004171. [DOI: 10.1002/14651858.CD004171] - DOI - PMC - PubMed
Carlisle 2021
    1. Carlisle JB. False individual patient data and zombie randomised controlled trials submitted to Anaesthesia. Anaesthesia 2021;76(4):472-9. [DOI: 10.1111/anae.15263] - DOI - PubMed
Clevenger 2015
    1. Clevenger B, Richards T. Pre-operative anaemia. Anaesthesia 2015;70:20-8, e6-8. - PubMed
Cochrane policy
    1. Cochrane Editors. Managing potentially problematic studies. Cochrane Database of Systematic Reviews: Editorial Policies. Available from https://www.cochranelibrary.com/cdsr/editorial-policies#problematic-studies 2020.
Cross 2014
    1. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Annals of the Rheumatic Diseases 2014;73:1323-30. - PubMed
Danninger 2015
    1. Danninger T, Memtsoudis SG. Tranexamic acid and orthopedic surgery - the search for the holy grail of blood conservation. Annals of Translational Medicine 2015;3(6):77. - PMC - PubMed
Desborough 2017a
    1. Desborough MJ, Oakland KA, Landoni G, Crivellari M, Doree C, Estcourt LJ, et al. Desmopressin for treatment of platelet dysfunction and reversal of antiplatelet agents: a systematic review and meta‐analysis of randomized controlled trials. Journal of Thrombosis and Haemostasis 2017;15(2):263-72. - PubMed
Desborough 2017b
    1. Desborough MJ, Oakland K, Brierley C, Bennett S, Doree C, Trivella M, et al. Desmopressin use for minimising perioperative blood transfusion. Cochrane Database of Systematic Reviews 2017, Issue 7. Art. No: CD001884. [DOI: 10.1002/14651858.CD001884.pub3] - DOI - PMC - PubMed
Dias 2010
    1. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Statistics in Medicine 2010;29:932-44. - PubMed
Dias 2018
    1. Dias S, Ades AE, Welton NJ, Jansen JP, Sutton AJ. Network Meta-Analysis for Decision Making. John Wiley & Sons Ltd, 2018.
Fillingham 2018
    1. Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, et al. The efficacy of tranexamic acid in total hip arthroplasty: a network meta-analysis. Journal of Arthroplasty 2018;33(10):3083-9.e4. - PubMed
Fillingham 2018a
    1. Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, et al. The efficacy of tranexamic acid in total knee arthroplasty: a network meta-analysis. Journal of Arthroplasty 2018;33(10):3090-8.e1. - PubMed
Fischer 2011
    1. Fischer CP, Wood CG, Shen J, Batiller J, Hart JC, Patel B, et al. A randomized trial of aprotinin-free fibrin sealant versus absorbable hemostat. Clinical and Applied Thrombosis/Hemostatis 2011;17(6):572-7. - PubMed
Franchini 2012
    1. Franchini M, Lippi G. Fibrinogen replacement therapy: a critical review of the literature. Blood Transfusion 2012;10(1):23-7. - PMC - PubMed
Gibbs 2023
    1. Gibbs VN, Geneen LJ, Champaneria R, Raval P, Dorée C, Brunskill SJ, et al. Pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic and long bone fractures. Cochrane Database of Systematic Reviews 2023, Issue 6. Art. No: CD013499. [DOI: 10.1002/14651858.CD013499] - DOI - PMC - PubMed
Henry 2011
    1. Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, et al. Anti‐fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No: CD001886. [DOI: 10.1002/14651858.CD001886.pub4] - DOI - PubMed
Higgins 2011a
    1. Higgins JP, Deeks JJ. Chapter 7: Selecting studies and collecting data. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Higgins 2011b
    1. Higgins JP, Altman DG, Sterne JA on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Higgins 2016
    1. Higgins JP, Sterne JA, Savović J, Page MJ, Hróbjartsson A, Boutron I, et al. A revised tool for assessing risk of bias in randomized trials. In: Chandler J, Clarke M, McKenzie J, Boutron I, Welch V (editors). Cochrane Methods. Cochrane Database of Systematic Reviews 2016;10(Suppl 1). [DOI: 10.1002/14651858.CD201601] - DOI
Higgins 2022
    1. Higgins JP, Eldridge S, Li T, editor(s). Chapter 23: Including variants on randomized trials. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
Hoaglin 2011
    1. Hoaglin DC, Hawkins N, Jansen JP, Scott DA, Itzler R, Cappelleri JC, et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR task force on indirect treatment comparisons good research practices: Part 2. Value in Health 2011;14(4):429-37. - PubMed
Jansen 2011
    1. Jansen JP, Fleurence R, Devine B, Itzler R, Barrett A, Hawkins N, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: Part 1. Value in Health 2011;14(4):417-28. - PubMed
Jansen 2013
    1. Jansen JP, Naci H. Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers. BMC Medicine 2013;11:159. - PMC - PubMed
Kasivisvanathan 2016
    1. Kasivisvanathan R, Ramesh V, Rao Baikady R, Nadaraja S. Preoperative anaemia is associated with increased allogeneic pack red cell transfusion in revision hip and knee joint arthroplasty: a retrospective analysis of 5387 patients over a 10-year period at a single high volume centre. Transfusion Medicine 2016;26(4):271-7. - PubMed
Kim 2017
    1. Kim JL, Park JH, Han SB, Cho IY, Jang KM. Allogeneic blood transfusion is a significant risk factor for surgical-site infection following total hip and knee arthroplasty: a meta-analysis. Journal of Arthroplasty 2017;32(1):320-5. - PubMed
Krahn 2013
    1. Krahn U, Binder H, Konig J. A graphical tool for locating inconsistency in network meta-analyses. BMC Medical Research Methodology 2013;13:35. - PMC - PubMed
Kumar 2014
    1. Kumar N, Chen Y, Zaw A, Nayak D, Ahmed Q, Soong R, et al. Use of intraoperative cell-salvage for autologous blood transfusions in metastatic spine tumour surgery: a systematic review. Lancet Oncology 2012;15:e33-41. - PubMed
Lasocki 2015
    1. Lasocki S, Krauspe R, Heymann C, Mezzacasa A, Chainey S, Spahn DR. PREPARE: the prevalence of perioperative anaemia and need for patient blood management in elective orthopaedic surgery: a multicentre, observational study. European Journal of Anaesthesiology 2015;32(3):160-7. - PubMed
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J, on behalf of the Cochrane Information Retrieval Methods Group. Chapter 6: Searching for studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Levy 2018
    1. Levy JH, Koster A, Quinones QJ, Milling TJ, Key NS. Antifibrinolytic therapy and perioperative considerations. Anesthesiology 2018;128:657-70. - PMC - PubMed
Li 2016
    1. Li J, Li HB, Zhai XC, Qin L, Jiang XQ, Zhang ZH. Topical use of topical fibrin sealant can reduce the need for transfusion, total blood loss and the volume of drainage in total knee and hip arthroplasty: A systematic review and meta-analysis of 1489 patients. International Journal of Surgery (London, England) 2016;36:127-37. - PubMed
Lu 2004
    1. Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Statistics in Medicine 2004;23(20):3105-24. - PubMed
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Journal of Clinical Epidemiology 2009;62(10):1006-12. - PubMed
Monsef 2014
    1. Monsef JB, Della Valle AG, Mayman DJ, Marx RG, Ranawat AS, Boettner F. The impact of blood management on length of stay after primary total knee arthroplasty. Open Orthopaedics Journal 2014;8:108-13. - PMC - PubMed
Munoz 2017
    1. Munoz M, Laso-Morales MJ, Gómez-Ramírez S, Cadellas M, Núñez-Matas MJ, García-Erce JA. Pre-operative haemoglobin levels and iron status in a large multicentre cohort of patients undergoing major elective surgery. Anaesthesia 2017;72(7):826-34. - PubMed
Myers 2019
    1. Myers SP, Kutcher ME, Rosengart MR, Sperry JL, Peitzman AB, Brown JB, et al. Tranexamic acid administration is associated with an increased risk of post-traumatic venous thromboembolism. Journal of Trauma and Acute Care Surgery 2019;86(1):20-7. [DOI: 10.1097/TA.0000000000002061] - DOI - PubMed
NCABT 2017
    1. The Patient Blood Management in Elective Surgery Working Group, on behalf of the National Comparative Audit in Blood Transfusion (NCABT) Steering Group. 2016 Patient blood management in adults undergoing elective, scheduled surgery. National Comparative Audit in Blood Transfusion (NCABT) Steering Group 2017.
NHSBT
    1. Portfolio and prices - Hospitals and Science - NHSBT (blood.co.uk). hospital.blood.co.uk/components/portfolio-and-prices/.
Nikolakopoulou 2020
    1. Nikolakopoulou A, Higgins JPT, Papakonstantinou T, Chaimani A, Del Giovane C, Egger M, et al. CINeMA: An approach for assessing confidence in the results of a network meta-analysis. PLOS Medicine 2020;17(4):e1003082. [PMID: ] - PMC - PubMed
NJR 2017a
    1. National Joint Registry. Public and Patient Guide to the NJR's 14th Annual Report 2017 Hip Replacement Edition. Report 2017:1-11.
NJR 2017b
    1. National Joint Registry. Public and Patient Guide to the NJR's 14th Annual Report 2017 Knee Replacement Edition. Report 2017:1-11.
NJR 2018
    1. National Joint Registry. 15th Annual Report 2018 National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. Report 2018:1-220.
Okamoto 1997
    1. Okamoto S, Hijikata‐Okunomiya A, Wanaka K, Okada Y, Okamoto U. Enzyme‐controlling medicines: introduction. Seminars in Thrombosis and Hemostasis 1997;23(6):492-501. - PubMed
Okholm 2022
    1. Okholm SH, Krog J, Hvas A-M. Tranexamic acid and its potential anti-inflammatory effect: a systematic review. In: Seminars in Thrombosis and Hemostasis. Thieme Medical Publishers, Inc., 2022. - PubMed
Pabinger 2015
    1. Pabinger C, Lothaller H, Geissler A. Utilization rates of knee-arthroplasty in OECD countries. Osteoarthritis and Cartilage 2015;23(10):1664-73. - PubMed
Pabinger 2018
    1. Pabinger C, Lothaller H, Portner N, Geissler A. Projections of hip arthroplasty in OECD countries up to 2050. HIP International 2018;28(5):498-506. - PubMed
Page 2021
    1. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. - PMC - PubMed
Palmer 2020
    1. Palmer AJR, Lloyd TD, Gibbs VN, Shah A, Dhiman P, Booth R, et al. The role of intra-operative cell salvage in patient blood management for revision hip arthroplasty: a prospective cohort study. Anaesthesia 2020;75(4):479-86. - PubMed
Park 2013
    1. Park JH, Rasouli MR, Mortazavi SM, Tokarski AT, Maltenfort MG, Parvizi J. Predictors of perioperative blood loss in total joint arthroplasty. Journal of Bone and Joint Surgery. American Volume 2013;95(19):1777-83. - PubMed
Pearson 2016
    1. Pearson K, Jensen H, Kander T, Schött U. Desmopressin in vitro effects on platelet function, monitored with Multiplate, ROTEM and Sonoclot. Scandinavian Journal of Clinical and Laboratory Investigation 2016;76(4):282-90. - PubMed
Review Manager Web [Computer program]
    1. Review Manager Web (RevMan Web). Version 7.1.1. The Cochrane Collaboration, 2023. Available at revman.cochrane.org.
Riaz 2019
    1. Riaz O, Aqil A, Asmar S, Vanker R, Hahnel J, Brew C, et al. Epsilon-aminocaproic acid versus tranexamic acid in total knee arthroplasty: a meta-analysis study. Journal of Orthopaedics and Traumatology 2019;20(1):28. - PMC - PubMed
Roberts 2013
    1. Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technology Assessment 2013;17(10):1-79. - PMC - PubMed
Roberts 2015
    1. Roberts I, Edwards P, Beecher D, Manno D, Sydenham E. The knowledge system underpinning healthcare is not fit for purpose and must change. BMJ 2015;350:h2463. - PubMed
Salanti 2014
    1. Salanti G, Del Giovane C, Chaimani A, Caldwell DM, Higgins JP. Evaluating the quality of evidence from a network meta-analysis. PLOS One 2014;9(7):e99682. - PMC - PubMed
Schulman 2012
    1. Schulman S. Pharmacologic tools to reduce bleeding in surgery. Hematology American Society of Hematology Education Program 2012;2012:517-21. - PubMed
Schünemann 2022
    1. Schünemann HJ, Higgins JPT, Vist GE, Glasziou P, Akl EA, Skoetz N et al. Chapter 14: Completing ‘Summary of findings’ tables and grading the certainty of the evidence. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
Simpson 2012
    1. Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C. Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database of Systematic Reviews 2012, Issue 3. Art. No: CD005011. [DOI: 10.1002/14651858.CD005011.pub4] - DOI - PMC - PubMed
Song 2003
    1. Song F, Altman DG, Glenny A-M, Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 2003;326(7387):472. - PMC - PubMed
Stokes 2011
    1. Stokes ME, Ye X, Shah M, Mercaldi K, Reynolds MW, Rupnow MF, et al. Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients. BMC Health Services Research 2011;11:135. - PMC - PubMed
Sutton 2008
    1. Sutton A, Ades AE, Cooper N, Abrams K. Use of indirect and mixed treatment comparisons for technology assessment. PharmacoEconomics 2008;26(9):753-67. - PubMed
Tinegate 2016
    1. Tinegate H, Pendry K, Murphy M, Babra P, Grant‐Casey J, Hopkinson C, et al. Where do all the red blood cells (RBCs) go? Results of a survey of RBC use in England and North Wales in 2014. Transfusion 2016;56:139-45. - PubMed
van der Valk 2009
    1. Valk R, Webers CA, Lumley T, Hendrikse F, Prins MH, Schouten JS. A network meta-analysis combined direct and indirect comparisons between glaucoma drugs to rank effectiveness in lowering intraocular pressure. Journal of Clinical Epidemiology 2009;62(12):1279-83. - PubMed
Walpole 2012
    1. Walpole SC, Prieto-Merino D, Edwards P, Cleland J, Stevens G, Roberts I. The weight of nations: an estimation of adult human biomass. BMC Public Health 2012;12(1):439. - PMC - PubMed
WHO Factsheet 2017
    1. Global Status Report on Blood Safety and Availability 2016. World Health Organization 2017 (accessed 1 November 2018).
Xu 2019a
    1. Xu S, Chen JY, Zheng Q, Lo NN, Chia SL, Tay KJD, et al. The safest and most efficacious route of tranexamic acid administration in total joint arthroplasty: a systematic review and network meta-analysis. Thrombosis Research 2019;176:61-6. - PubMed
Yepes‐Nuñez 2019
    1. Yepes-Nuñez JJ, Li SA, Guyatt G, Jack SM, Brozek JL, Beyene J, et al. Development of the summary of findings table for network meta-analysis. Journal of Clinical Epidemiology 2019;115:1-13. - PubMed
Zhang 2014
    1. Zhang W, Li N, Chen S, Tan Y, Al-Aidaros M, Chen L. The effects of a tourniquet used in total knee 706 arthroplasty: a meta-analysis. Journal of Orthopaedic Surgery and Research 2014;9:13. - PMC - PubMed

References to other published versions of this review

Gibbs 2019
    1. Gibbs VN, Champaneria R, Palmer A, Doree C, Estcourt LJ. Pharmacological interventions for the prevention of bleeding in people undergoing elective hip or knee surgery: a systematic review and network meta‐analysis. Cochrane Database of Systematic Reviews 2019, Issue 3. Art. No: CD013295. [DOI: 10.1002/14651858.CD013295] - DOI - PMC - PubMed

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