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Meta-Analysis
. 2023 Jun 5;6(6):CD013499.
doi: 10.1002/14651858.CD013499.pub2.

Pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic and long bone fractures

Victoria N Gibbs #  1 , Louise J Geneen #  1   2 , Rita Champaneria  1   2 , Parag Raval  3 , Carolyn Dorée  1   2 , Susan J Brunskill  1   2 , Alex Novak  4 , Antony Jr Palmer  5 , Lise J Estcourt  6
Affiliations
Meta-Analysis

Pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic and long bone fractures

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

Abstract

Background: Pelvic, hip, and long bone fractures can result in significant bleeding at the time of injury, with further blood loss if they are treated with surgical fixation. People undergoing surgery are therefore at risk of requiring a blood transfusion and may be at risk of peri-operative anaemia. Pharmacological interventions for blood conservation may reduce the risk of requiring an allogeneic blood transfusion and associated complications.

Objectives: To assess the effectiveness of different pharmacological interventions for reducing blood loss in definitive surgical fixation of the hip, pelvic, and long bones.

Search methods: We used a predefined search strategy to search CENTRAL, MEDLINE, PubMed, Embase, CINAHL, Transfusion Evidence Library, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) from inception to 7 April 2022, without restrictions on language, year, or publication status. We handsearched reference lists of included trials to identify further relevant trials. We contacted authors of ongoing trials to acquire any unpublished data.

Selection criteria: We included randomised controlled trials (RCTs) of people who underwent trauma (non-elective) surgery for definitive fixation of hip, pelvic, and long bone (pelvis, tibia, femur, humerus, radius, ulna and clavicle) fractures only. There were no restrictions on gender, ethnicity, or age. We excluded planned (elective) procedures (e.g. scheduled total hip arthroplasty), and studies published since 2010 that had not been prospectively registered. Eligible interventions included: antifibrinolytics (tranexamic acid, aprotinin, epsilon-aminocaproic acid), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants, and non-fibrin sealants.

Data collection and analysis: Two review authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using GRADE. We did not perform a network meta-analysis due to lack of data.

Main results: We included 13 RCTs (929 participants), published between 2005 and 2021. Three trials did not report any of our predefined outcomes and so were not included in quantitative analyses (all were tranexamic acid versus placebo). We identified three comparisons of interest: intravenous tranexamic acid versus placebo; topical tranexamic acid versus placebo; and recombinant factor VIIa versus placebo. We rated the certainty of evidence as very low to low across all outcomes. Comparison 1. Intravenous tranexamic acid versus placebo Intravenous tranexamic acid compared to placebo may reduce the risk of requiring an allogeneic blood transfusion up to 30 days (RR 0.48, 95% CI 0.34 to 0.69; 6 RCTs, 457 participants; low-certainty evidence) and may result in little to no difference in all-cause mortality (Peto odds ratio (Peto OR) 0.38, 95% CI 0.05 to 2.77; 2 RCTs, 147 participants; low-certainty evidence). It may result in little to no difference in risk of participants experiencing myocardial infarction (risk difference (RD) 0.00, 95% CI -0.03 to 0.03; 2 RCTs, 199 participants; low-certainty evidence), and cerebrovascular accident/stroke (RD 0.00, 95% CI -0.02 to 0.02; 3 RCTs, 324 participants; low-certainty evidence). We are uncertain if there is a difference between groups for risk of deep vein thrombosis (Peto OR 2.15, 95% CI 0.22 to 21.35; 4 RCTs, 329 participants, very low-certainty evidence), pulmonary embolism (Peto OR 1.08, 95% CI 0.07 to 17.66; 4 RCTs, 329 participants; very low-certainty evidence), and suspected serious drug reactions (RD 0.00, 95% CI -0.03 to 0.03; 2 RCTs, 185 participants; very low-certainty evidence). No data were available for number of red blood cell units transfused, reoperation, or acute transfusion reaction. We downgraded the certainty of the evidence for imprecision (wide confidence intervals around the estimate and small sample size, particularly for rare events), and risk of bias (unclear or high risk methods of blinding and allocation concealment in the assessment of subjective measures), and upgraded the evidence for transfusion requirement for a large effect. Comparison 2. Topical tranexamic acid versus placebo We are uncertain if there is a difference between topical tranexamic acid and placebo for risk of requiring an allogeneic blood transfusion (RR 0.31, 95% CI 0.08 to 1.22; 2 RCTs, 101 participants), all-cause mortality (RD 0.00, 95% CI -0.10 to 0.10; 1 RCT, 36 participants), risk of participants experiencing myocardial infarction (Peto OR 0.15, 95% CI 0.00 to 7.62; 1 RCT, 36 participants), cerebrovascular accident/stroke (RD 0.00, 95% CI -0.06 to 0.06; 1 RCT, 65 participants); and deep vein thrombosis (Peto OR 1.11, 95% CI 0.07 to 17.77; 2 RCTs, 101 participants). All outcomes reported were very low-certainty evidence. No data were available for number of red blood cell units transfused, reoperation, incidence of pulmonary embolism, acute transfusion reaction, or suspected serious drug reactions. We downgraded the certainty of the evidence for imprecision (wide confidence intervals around the estimate and small sample size, particularly for rare events), inconsistency (moderate heterogeneity), and risk of bias (unclear or high risk methods of blinding and allocation concealment in the assessment of subjective measures, and high risk of attrition and reporting biases in one trial). Comparison 3. Recombinant factor VIIa versus placebo Only one RCT of 48 participants reported data for recombinant factor VIIa versus placebo, so we have not presented the results here.

Authors' conclusions: We cannot draw conclusions from the current evidence due to lack of data. Most published studies included in our analyses assessed the use of tranexamic acid (compared to placebo, or using different routes of administration). We identified 27 prospectively registered ongoing RCTs (total target recruitment of 4177 participants by end of 2023). The ongoing trials create six new comparisons: tranexamic acid (tablet + injection) versus placebo; intravenous tranexamic acid versus oral tranexamic acid; topical tranexamic acid versus oral tranexamic acid; different intravenous tranexamic acid dosing regimes; topical tranexamic acid versus topical fibrin glue; and fibrinogen (injection) versus placebo.

PubMed Disclaimer

Conflict of interest statement

VNG: funded by an NIHR Cochrane Programme Grant for a series of reviews

RC: funded by an NIHR Cochrane Programme Grant for a series of reviews

LJG: none

PR: none

CD: none

SJB: none. SJB is a Cochrane editor (with Cochrane Haematology) and was not involved with the editorial process for this review.

AN: none

AJRP: none

LJE: none. LJE is a Cochrane editor (with Cochrane Haematology) and was not involved with the editorial process for this review.

Figures

1
1
Study flow diagram
2
2
Methodological quality summary: review authors' risk of bias judgements about each methodological quality item for each included study.
3
3
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies
4
4
Four‐node network for included studies. Node size represents sample size, solid lines represent direct comparisons (thickness depicting more studies contributing to the comparison), and dashed lines depict potential indirect comparisons. This is an original image, created by one author (LJG)
1.1
1.1. Analysis
Comparison 1: TXA (IV) vs placebo, Outcome 1: Risk of requiring allogeneic blood transfusion (30 days)
1.2
1.2. Analysis
Comparison 1: TXA (IV) vs placebo, Outcome 2: All‐cause mortality (30 days)
1.3
1.3. Analysis
Comparison 1: TXA (IV) vs placebo, Outcome 3: Risk of MI (30 days)
1.4
1.4. Analysis
Comparison 1: TXA (IV) vs placebo, Outcome 4: Risk of CVA/stroke (30 days)
1.5
1.5. Analysis
Comparison 1: TXA (IV) vs placebo, Outcome 5: Risk of DVT (30 days)
1.6
1.6. Analysis
Comparison 1: TXA (IV) vs placebo, Outcome 6: Risk of PE (30 days)
1.7
1.7. Analysis
Comparison 1: TXA (IV) vs placebo, Outcome 7: Risk of suspected serious drug reactions (30 days)
2.1
2.1. Analysis
Comparison 2: TXA (topical) vs placebo, Outcome 1: Risk of requiring allogeneic blood transfusion (30 days)
2.2
2.2. Analysis
Comparison 2: TXA (topical) vs placebo, Outcome 2: All‐cause mortality (30 days)
2.3
2.3. Analysis
Comparison 2: TXA (topical) vs placebo, Outcome 3: Risk of MI (30 days)
2.4
2.4. Analysis
Comparison 2: TXA (topical) vs placebo, Outcome 4: Risk of CVA/stroke (30 days)
2.5
2.5. Analysis
Comparison 2: TXA (topical) vs placebo, Outcome 5: Risk of DVT (30 days)
3.1
3.1. Analysis
Comparison 3: rFVIIa vs placebo, Outcome 1: Risk of requiring allogeneic blood transfusion (30 days)
3.2
3.2. Analysis
Comparison 3: rFVIIa vs placebo, Outcome 2: Re‐operation due to bleeding (7 days)
3.3
3.3. Analysis
Comparison 3: rFVIIa vs placebo, Outcome 3: Risk of DVT (30 days)
3.4
3.4. Analysis
Comparison 3: rFVIIa vs placebo, Outcome 4: Risk of PE (30 days)
3.5
3.5. Analysis
Comparison 3: rFVIIa vs placebo, Outcome 5: Risk of suspected serious drug reaction (30 days)
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013499

References

References to studies included in this review

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Parish 2021 {published data only}
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References to studies excluded from this review

ACTRN 12613000323729 {published data only}
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ACTRN 12613001043729 {published data only}
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Baruah 2016 {published data only}
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Bradley 2019 {published data only}
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Cerciello 2014 {published data only}
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ChiCTR 1800016634 {published data only}
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ChiCTR 1800019266 {published data only}
    1. ChiCTR1800019266 . The blood sparing, anti-fibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total hip arthroplasty: a randomized controlled trial . http://www.chictr.org.cn/showprojen.aspx?proj=32412 Date of registration: 2018-11-02 (retrospective).
ChiCTR 1900027435 {published data only}
    1. ChiCTR1900027435 . Safety and efficacy of sequential application of TXA in reducing perioperative blood loss in hip fractures: a prospective randomized controlled trial . http://www.chictr.org.cn/hvshowproject.aspx?id=32751 (retrospective) Version creation time 2020/5/10.
ChiCTR 2000032102 {published data only}
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ChiCTR 2000032836 {published data only}
    1. ChiCTR2000032836. The efficacy and safety of early sequential boluses of multi-dose oral tranexamic acid on reducing perioperative blood loss among hip fractures: a prospective randomized controlled trial. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2000032836 Date of registration: 2020-05-12 (retrospective).
ChiCTR 2000033135 {published data only}
    1. ChiCTR2000033135. Effect of TXA on reducing perioperative hidden blood loss in inter-trochanteric fracture treated with PFNA. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2000033135 Date of registration: 2020-05-22 (retrospective).
ChiCTR 2000034882 {published data only}
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ChiCTR‐IDR‐17010966 {published data only}
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ChiCTR‐TRC‐14004379 {published data only}
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Chin 2020 {published data only}
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Clave 2019 {published data only}
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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 & Analgesia 2000;91(5):1124-30. [DOI: 10.1213/00000539-200011000-00014] - DOI - PubMed
Fischer 2013 {published data only}
    1. Fischer CP, Bochicchio G, Shen J, Patel B, Batiller J, Hart JC. A prospective, randomized, controlled trial of the efficacy and safety of fibrin pad as an adjunct to control soft tissue bleeding during abdominal, retroperitoneal, pelvic, and thoracic surgery. Journal of the American College of Surgeons 2013;217(3):385-93. [DOI: ] - 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. Shock 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. [DOI: ] [PMID: ] - PMC - PubMed
Flordal 1991 {published data only}
    1. Flordal PA, Ljungstrom KG, Svensson J, Ekman B, Neander G. Effects of coagulation and fibrinolysis of desmopressin in patients undergoing total hip replacement. Thrombosis and Haemostasis 1991;66(6):652-6. - 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. [DOI: ] - PubMed
Fraval 2018 {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 2018;29(3):239-44. [DOI: ] [PMID: ] - PubMed
Galué 2015 {published data only}
    1. Galué-Sanchez J, Marquez-Andrade F, Reyna-Villasmil E, Mejia-Montilla J, Reyna-Villasmil N, Torres-Cepeda D, et al. Tranexamic acid in blood loss of hip fracture surgery. MedULA 2015;24(2):67-71.
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. British Journal of Anaesthesia 1998;80 Suppl 1:Abstract no. A270.
Gausden 2016 {published data only}
    1. Gausden EB, Garner MR, Warner SJ, Levack A, Nellestein AM, Tedore T, et al. Tranexamic acid in hip fracture patients: a protocol for a randomised, placebo controlled trial on the efficacy of tranexamic acid in reducing blood loss in hip fracture patients. BMJ Open 2016;6(6):e010676. [DOI: ] - PMC - PubMed
    1. NCT01940536. The effect of tranexamic acid on transfusion rates in intertrochanteric hip fractures. https://clinicaltrials.gov/ct2/show/record/NCT01940536?view=record First posted: 12 September 2013 (prospective).
Gillespie 2015 {published data only}
    1. Gillespie R, Shishani Y, Joseph S, Streit JJ, Gobezie R. Neer Award 2015: a randomized, prospective evaluation on the effectiveness of tranexamic acid in reducing blood loss after total shoulder arthroplasty. Journal of Shoulder & Elbow Surgery 2015;24(11):1679-84. [DOI: ] [PMID: ] - 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. [DOI: ] - 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. [DOI: ] [PMID: ] - PMC - PubMed
Hourlier 2012 {published data only}
    1. Hourlier H, Fennema P. Reducing morbidity in total hip replacement: a prospective randomised trial of 2 tranexamic acid regimens. HIP International 2012;22(4):475. [DOI: ] - PMC - PubMed
Huang 2021 {published data only}
    1. Huang S, Hu W, Shen Z, Wang M. Application of tranexamic acid intravenous drip before internal fixation in the treatment of elderly patients with unstable intertrochanteric fracture. Acta Medica Mediterranea 2021;37(2):1183-7. [DOI: ]
IRCT 201111198131N {published data only}
    1. IRCT201111198131N1. Comparison of femoral shaft fracture bleeding in the two methods of tranexamic acid and controled hypotension. https://www.irct.ir/trial/8560 Registration date: 2012-02-27 (retrospective).
IRCT 2013100414302N {published data only}
    1. IRCT2013100414302N3. The effect of intravenous tranexamic acid on bleeding during and after femoral fracture surgeries under general anesthesia. https://en.irct.ir/trial/13919 Registration date: 2013-11-01 (retrospective).
IRCT 2016061328437N {published data only}
    1. IRCT2016061328437N1. Tranexamic acid effect on bleeding in femoral fracture surgery [Comparison of the tranexamic acid effect with the control group on bleeding in patients undergoing femoral shaft fracture surgery in Khatam al Anbiya hospital in Zahedan in 2016-2017]. http://en.irct.ir/trial/23079 Registration date: 2016-08-20 (retrospective).
IRCT 2017050126328N {published data only}
    1. IRCT2017050126328N3. Effect of intraoperative infusion of tranexamic acid on blood loss volume during femoral fracture surgery: a double-blinded clinical trial [Controlling femoral fracture surgery bleeding by tranexamic acid]. https://en.irct.ir/trial/21840 Registration date: 2017-06-27 (retrospective).
IRCT 20180404039188N2 {published data only}
    1. IRCT20180404039188N2. Effect of Intravenous tranexamic acid on blood loss in pelvic and acetabular fractures in patients referred to Taleghani and Emam Hosein Hospital of Tehran between 2019-2020. https://en.irct.ir/trial/51816 Registration date: 2021-05-10 (retrospective).
IRCT 20180422039382N {published data only}
    1. IRCT20180422039382N1. Effect of tranexamic acid on bleeding after femural fracture surgery. https://en.irct.ir/trial/30870 Date of registration: 2018-06-10 (retrospective).
IRCT 20200114046133N1 {published data only}
    1. IRCT20200114046133N1. Study of effect of tranexamic acid on the amount of bleeding during surgery and surgeons satisfaction in intertrochantric fracture . https://en.irct.ir/trial/45089 Registration date: 2020-02-02 (retrospective).
IRCT 20211208053326N1 {published data only}
    1. IRCT20211208053326N1. The effect of intravenous tranexamic acid on postoperative bleeding in patients with shaft femoral fractures. https://en.irct.ir/trial/61116 Registration date: 2022-01-30 (retrospective).
    1. IRCT20211208053326N1. The effect of intravenous tranexamic acid on postoperative bleeding in patients with shaft femoral fractures. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20211208053326N1 Date of registration: 2022-01-30 (retrospective).
ISRCTN 02543733 {published data only}
    1. ISRCTN02543733. St George's Hospital UK Study of the use of recombinant factor VIIa in pelvic fracture and acetabular reconstruction. https://www.isrctn.com/ISRCTN02543733 Registration date: 12/09/2003 (retrospective). [DOI: ]
ISRCTN 55488814 {published data only}
    1. ISRCTN55488814. Reduction of allogenic blood transfusion and increased activation of coagulation by re-infusion of post-operative autologous wound blood in patients undergoing total knee and total hip replacement. https://www.isrctn.com/ISRCTN55488814 Registration date: 12/03/2012 (retrospective). [DOI: ]
ISRCTN 58762744 {published data only}
    1. ISRCTN58762744 . A randomised controlled trial of the use of topical application of tranexamic acid in primary cemented total hip replacement. https://www.isrctn.com/ISRCTN58762744 Registration date: 29/09/2006 (retrospective). [DOI: ]
ISRCTN 59245192 {published data only}
    1. ISRCTN59245192. Topical tranexamic acid in total hip replacement. https://www.isrctn.com/ISRCTN59245192 Registration date: 24/04/2012 (retrospective). [DOI: ]
Ivie 2016 {published data only}
    1. Ivie R, Maniker R. Tranexamic acid dose and perioperative blood loss in total hip and knee arthroplasty: a prospective, randomized, double-blind trial. Regional Anesthesia and Pain Medicine. Conference: 41st Annual Regional Anesthesiology and Acute Pain Medicine Meeting of the American Society of Regional Anesthesia and Pain Medicine, ASRA 2016;41(5):Abstract no. 1512.
Jans 2016 {published data only}
    1. Jans O, Grevstad U, Mandoe H, Kehlet H, Johansson PI. A randomized trial of the effect of low dose epinephrine infusion in addition to tranexamic acid on blood loss during total hip arthroplasty. British Journal of Anaesthesia 2016;116(3):357-62. [DOI: ] - 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. [DOI: ] - PubMed
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    1. Jordan M, Castillon P, Salomo M, Hernandez JA, Ruiz L, Mora JM, et al. Prevention of postoperative bleeding: a multicentre, randomised, parallel, controlled clinical trial, evaluating the efficacy of tranexamic acid and fibrin glue in patients undergoing interventions for sub-capital femoral fracture. Basic and Clinical Pharmacology and Toxicology 2016;119 Suppl 1:28.
Jordan 2019 {published data only}
    1. Jordan M, Aguilera X, Gonzalez JC, Castillon P, Salomo M, Hernandez JA, et al, Group TRANEXFER. Prevention of postoperative bleeding in hip fractures treated with prosthetic replacement: efficacy and safety of fibrin sealant and tranexamic acid. A randomised controlled clinical trial (TRANEXFER study). Archives of Orthopaedic & Trauma Surgery 2019;139(5):597-604. [DOI: ] - PubMed
Koea 2015 {published data only}
    1. EUCTR 2008-004835-39. A phase III randomized, controlled, superiority study evaluating the fibrin pad versus standard of care treatment in controlling severe soft tissue bleeding during abdominal, retroperitoneal, pelvic, and thoracic surgery. https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-004835-39/GB Date on which this record was first entered in the EudraCT database: 2008-10-16 (prospective).
    1. Koea J, Baldwin P, Shen J, Patel B, Batiller J, Arnaud A, et al. Erratum to: Safety and hemostatic effectiveness of the fibrin pad for severe soft-tissue bleeding during abdominal, retroperitoneal, pelvic, and thoracic (non-cardiac) surgery: a randomized, controlled, superiority trial. World Journal of Surgery 2015;39(10):2610. [DOI: ] - PubMed
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Lack 2017 {published data only}
    1. Lack WD, Crist BD, Seymour RB, Harvin W, Karunakar MA, Group TXA Study. Effect of tranexamic acid on transfusion: a randomized clinical trial in acetabular fracture surgery. Journal of Orthopaedic Trauma 2017;31(10):526-30. [DOI: ] [PMID: ] - PubMed
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    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. [DOI: ] - PubMed
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    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. British Journal of Anaesthesia 1998;80 Suppl 1:Abstract no. A271.
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. [DOI: ]
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    1. Mukherjee M, Biswas C, Chatterjee S, Bandyopadhyay BK. Comparative study of efficacy of reduction of blood loss by tranexamic acid and epsilon aminocaproic acid for orthopedic femoral surgeries. Anaesthesia, Pain and Intensive Care 2016;20(4):417-21.
Na 2016 {published data only}
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    1. IRCT201012264784N2. Effect of prophylactic administration of fibrinogen concentrate on volume of transfused packed RBC during and after total hip arthroplasty. http://en.irct.ir/trial/5126 Date of registration: 2012-06-11 (retrospective).
    1. Najafi A, Shariat Moharari R, Orandi AA, Etezadi F, Sanatkar M, 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
Narkbunnam 2021 {published data only}
    1. Narkbunnam R, Chompoonutprapa A, Ruangsomboon P, Udomkiat P, Chareancholvanich K, Pornrattanamaneewong C. Blood loss and transfusion rate compared among different dosing regimens of tranexamic acid administration in patients undergoing hip hemiarthroplasty for femoral neck fracture: A randomized controlled trial. Injury 2021;52(10):2986-90. [DOI: ] - PubMed
    1. TCTR20200506007. Comparison among different regimens of intravenous tranexamic acid for reducing blood transfusion in femoral neck fracture after hemiarthroplasty: a randomized controlled trial. https://www.thaiclinicaltrials.org/show/TCTR20200506007 First posted date: 6 May 2020 (retrospective).
NCT00375440 {published data only}
    1. NCT00375440. Tranexamic acid study. https://clinicaltrials.gov/ct2/show/study/NCT00375440 First posted: 13 September 2006 (retrospective).
NCT00658723 {published data only}
    1. NCT00658723. The fibrin patch soft tissue study. https://clinicaltrials.gov/ct2/show/study/NCT00658723 First posted: 15 April 2008 (retrospective).
NCT00824564 {published data only}
    1. NCT00824564. Study of tranexamic acid for the reduction of blood loss in patients undergoing surgery for long bone fracture. https://clinicaltrials.gov/ct2/show/study/NCT00824564 First posted: 16 January 2009 (prospective).
NCT01199627 {published data only}
    1. NCT01199627. Tranexamic acid versus placebo for the reduction of blood loss in total hip replacement surgery (TXA-CRT). https://clinicaltrials.gov/ct2/show/study/NCT01199627 First posted: 13 September 2010 (prospective).
NCT01326403 {published data only}
    1. NCT01326403. Tranexamic acid in hip fracture patients. https://clinicaltrials.gov/ct2/show/study/NCT01326403 First posted: 30 March 2011 (prospective).
NCT01535781 {published data only}
    1. NCT01535781. Study of the effect of tranexamic acid administered to patients with hip fractures. Can blood loss be reduced? https://clinicaltrials.gov/ct2/show/study/NCT01535781 First posted: 20 February 2012 (retrospective).
NCT01714336 {published data only}
    1. NCT01714336. Does tranexamic acid reduce the need for blood transfusions in patients undergoing hip fracture surgery? https://clinicaltrials.gov/ct2/show/study/NCT01714336 First posted: 25 October 2012 (retrospective).
NCT01866943 {published data only}
    1. NCT01866943. Role of topical tranexamic acid in total hip arthroplasty (TXA). https://clinicaltrials.gov/ct2/show/study/NCT01866943 First posted: 3 June 2013 (retrospective).
NCT02043132 {published data only}
    1. NCT02043132. Tranexamic acid in reverse total shoulder arthroplasty (TXA). https://clinicaltrials.gov/ct2/show/study/NCT02043132 First posted: 23 January 2014 (retrospective).
NCT02051686 {published data only}
    1. NCT02051686. Hemostasis in open acetabulum and pelvic ring surgery using tranexamic acid (TXA). https://clinicaltrials.gov/ct2/show/study/NCT02051686 First posted: 31 January 2014 (retrospective).
NCT02080494 {published data only}
    1. NCT02080494. Tranexamic acid in orthopaedic trauma surgery. https://clinicaltrials.gov/ct2/show/study/NCT02080494 First posted: 6 March 2014 (retrospective).
NCT02150720 {published data only}
    1. NCT02150720. Prevention of postoperative bleeding in subcapital femoral fractures (TRANEXFER). https://clinicaltrials.gov/ct2/show/study/NCT02150720 First posted: 30 May 2014 (retrospective).
NCT02164565 {published data only}
    1. NCT02164565. The use of tranexamic acid (TXA) intravenously, to reduce blood loss in proximal femur surgery. https://clinicaltrials.gov/ct2/show/study/NCT02164565 First posted: 16 June 2014 (prospective).
NCT02233101 {published data only}
    1. NCT02233101. Oral vs. intravenous TXA study proposal: TJA. https://www.clinicaltrials.gov/ct2/show/study/NCT02233101 First posted: 8 September 2014 (retrospective).
NCT02252497 {published data only}
    1. NCT02252497. Tranexamic acid in total hip arthroplasty. (PORTO). https://clinicaltrials.gov/ct2/show/study/NCT02252497 First posted: 30 September 2014 (retrospective).
NCT02569658 {published data only}
    1. NCT02569658. Investigation of intravenous tranexamic acid with anatomic and reverse total shoulder arthroplasty. https://clinicaltrials.gov/ct2/show/study/NCT02569658 First posted: 7 October 2015 (retrospective).
NCT02580227 {published data only}
    1. NCT02580227. Tranexamic acid in intertrochanteric and subtrochanteric femur fractures. https://clinicaltrials.gov/ct2/show/study/NCT02580227 First posted: 20 October 2015 (retrospective).
NCT02584725 {published data only}
    1. NCT02584725. Tranexamic acid dosing for total joint arthroplasty. https://clinicaltrials.gov/ct2/show/study/NCT02584725 First posted: 23 October 2015 (retrospective).
NCT02644473 {published data only}
    1. NCT02644473. Safety of topical tranexamic acid in total joint arthroplasty in high risk patients. https://clinicaltrials.gov/ct2/show/study/NCT02644473 First posted: 31 December 2015 (prospective).
NCT02684851 {published data only}
    1. NCT02684851. The use of tranexamic acid to reduce blood loss in acetabular surgery (TXA). https://clinicaltrials.gov/ct2/show/study/NCT02684851 First posted: 18 February 2016 (retrospective).
NCT02747615 {published data only}
    1. NCT02747615. Efficacy of preoperative autologous blood donation and tranexamic acid in revision total hip arthroplasty. https://clinicaltrials.gov/ct2/show/study/NCT02747615 First posted: 22 April 2016 (retrospective).
NCT02908516 {published data only}
    1. NCT02908516. Safety and efficacy of oral TXA in reducing blood loss and transfusion in hip fractures. https://clinicaltrials.gov/ct2/show/study/NCT02908516 First posted: 21 September, 2016 (prospective).
NCT02947529 {published data only}
    1. NCT02947529. Tranexamic acid use in acute hip fractures. https://clinicaltrials.gov/ct2/show/record/NCT02947529 First posted: 28 October 2016 (retrospective).
NCT03019198 {published data only}
    1. NCT03019198. Tranexamic acid in patients undergoing total hip arthroplasty in a Brazilian reference orthopedic center: a randomized controlled trial. https://clinicaltrials.gov/ct2/show/study/NCT03019198 First posted: 12 January 2017 (retrospective).
NCT03251469 {published data only}
    1. NCT03251469. Single dose of tranexamic acid and blood loss, in elderly patients with hip fracture. https://clinicaltrials.gov/ct2/show/study/NCT03251469 First posted: 16 August 2017 (retrospective).
NCT03653429 {published data only}
    1. NCT03653429. Efficacy of tranexamic acid in foot and ankle surgeries. https://clinicaltrials.gov/ct2/show/study/NCT03653429 First posted: 31 August 2018 (retrospective).
NCT03679481 {published data only}
    1. NCT03679481. The effect of tranexamic acid on blood loss and transfusion requirements following open femur fracture surgery. https://clinicaltrials.gov/ct2/show/study/NCT03679481 First posted: 2- September 2018 (prospective).
NCT03825939 {published data only}
    1. NCT03825939. Evaluating the use of tranexamic acid (TXA) in total joint arthroplasty. https://clinicaltrials.gov/ct2/show/study/NCT03825939 First posted: 1 February 2019 (retrospective).
NCT04488367 {published data only}
    1. NCT04488367. Blood loss after early TXA in hip fractures. https://clinicaltrials.gov/ct2/show/study/NCT04488367 First posted: 28 July 2020 (retrospective).
NCT04696224 {published data only}
    1. NCT04696224. Comparative use of tranexamic acid intravenous and topical application in intertrochanteric fractures with PFNA. https://clinicaltrials.gov/ct2/show/NCT04696224 First posted: 6 January 2021 (retrospective).
NCT04803591 {published data only}
    1. NCT04803591. This is a study to verify if tranexamic acid can reduce the anemia after a femoral shaft fractures surgery (ORL-ORT-023). https://clinicaltrials.gov/ct2/show/NCT04803591 First posted: 17 March 2021 (prospective).
NCT04986813 {published data only}
    1. NCT04986813. Tranexamic acid in trauma surgery tranexamic acid in trauma surgery tranexamic acid in trauma surgery. https://clinicaltrials.gov/ct2/show/NCT04986813 First posted: 3 August 2021 (retrospective).
NCT05047133 {published data only}
    1. NCT05047133. Effect of early administration of TXA in adult hip fractures. https://clinicaltrials.gov/ct2/show/NCT05047133 First posted: 16 September 2021 (retrospective).
Nikolaou 2021 {published data only}
    1. Nikolaou VS, Masouros P, Floros T, Chronopoulos E, Skertsou M, Babis GC. Infographic: single dose of tranexamic acid effectively reduces blood loss and transfusion rates in elderly patients undergoing surgery for hip fracture: a randomized controlled trial. Bone and Joint Journal 2021;103-B:440-1. [DOI: ] - PubMed
    1. Nikolaou VS, Masouros P, Floros T, Chronopoulos E, Skertsou M, Babis GC. Single dose of tranexamic acid effectively reduces blood loss and transfusion rates in elderly patients undergoing surgery for hip fracture: a randomized controlled trial. Bone and Joint Journal 2021;103-B(3):442-8. [DOI: ] - PubMed
North 2016 {published data only}
    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 (letter to the editor). Journal of Arthroplasty 2016;31(4):928-9. [DOI: ] - PubMed
    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. [DOI: 10.1016/j.arth.2015.11.003] - DOI - PubMed
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    1. Ozay K, Dogu H, Erkal H, Aydym F, Azali G, Arikan Z. Aprotinin infusion during major orthopaedic surgery. British Journal of Anaesthesia 1995;74 Suppl 1:61 (abstract no. A201).
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. [DOI: ] [PMID: ] - PubMed
Qiu 2019 {published data only}
    1. Qiu J, Sun X, Zhang W, Ke X, Yang G, Zhang L. Effect of topical tranexamic acid in total hip arthroplasty patients who receive continuous aspirin for prevention of cardiovascular or cerebrovascular events: a prospective randomized study. Orthopaedics & Traumatology, Surgery & Research : OTSR 2019;105(7):1327-32. [DOI: ] - 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 & Joint Surgery - British Volume 2009;91(6):776-83. [DOI: ] - PubMed
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    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 & Analgesia 2002;95(2):287-93. [DOI: 10.1213/00000539-200208000-00005] - DOI - PubMed
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    1. Saravanan R, Venkatraman R, Karthik K, Pushparani A. Efficacy of different doses and timing of tranexamic acid in major orthopedic surgeries: a randomized trial [Eficácia de diferentes doses e esquemas de administração de ácido tranexâmico em cirurgias ortopédicas de grande porte: estudo randomizado]. Brazilian Journal of Anesthesiology 2020;70(4):311-7. [DOI: ] - PMC - PubMed
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    1. R Champaneria. Personal email to Dr Shodipo Olaoluwa to ask for a trial registration number Email sent on 24 May 2022.
    1. Shodipo OM, Jatto HI, Ramat AM, Ibrahim SS, Ajiboye LO, Arojuraye SA, et al. Comparison of single versus double tranexamic acid dose regimens in reducing post-operative blood loss following intramedullary nailing of femoral fracture nonunions. International Orthopaedics 2022;46(1):97-101. [DOI: ] - PubMed
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    1. TCTR20201224005. Topical tranexamic acid effect on blood loss in hip fractured patients undergoing cemented bipolar hemiarthroplasty: a randomized controlled trial. https://www.thaiclinicaltrials.org/show/TCTR20201224005 First posted: 24 December 2020 (retrospective).
TCTR 202102090010 {published data only}
    1. TCTR202102090010. Efficacy of peri-articular tranexamic acid for hip replacement surgery in patients with fracture neck of femur: a randomized controlled trial. https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR202102090010 Date of registration: 09/02/2021 (retrospective).
    1. TCTR202102090010. Efficacy of peri-articular tranexamic acid for hip replacement surgery in patients with fracture neck of femur: a randomized controlled trial. https://www.thaiclinicaltrials.org/show/TCTR202102090010 First posted: 09 February 2021 (retrospective).
TCTR 20220104001 {published data only}
    1. TCTR20220104001. The efficacy of tranexamic acid to reduce perioperative blood loss and blood transfusion in patients undergoing distal femur fracture surgery. https://www.thaiclinicaltrials.org/show/TCTR20220104001 First posted: 04 January 2022 (retrospective).
Tengberg 2016 {published data only}
    1. NCT01535781. Study of the effect of tranexamic acid administered to patients with hip fractures. can blood loss be reduced? https://clinicaltrials.gov/ct2/show/NCT01535781 First posted: 20 February 2012 (retrospective).
    1. Tengberg PT, Foss NB, Palm H, Kallemose T, Troelsen A. Tranexamic acid reduces blood loss in patients with extracapsular fractures of the hip: results of a randomised controlled trial. Bone & Joint Journal 2016;98-B(6):747-53. [DOI: ] - PubMed
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 surgery. Indian Journal of Anaesthesia 2017;61(3):235-9. [DOI: ] [PMID: ] - PMC - PubMed
Tulaja Prasad 2021 {published data only}
    1. Tulaja Prasad PV, Bennur AT, Pragadeeshwaran G. Efficacy of tranexamic acid in reducing perioperative blood loss in lower limb orthopaedic surgeries: a prospective randomised single blinded study. European Journal of Molecular and Clinical Medicine 2021;8(4):2024-8.
Van Elst 2013 {published data only}
    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 approach. In: American Academy of Orthopaedic Surgeons Annual Meeting. 2013:Poster P093.
Vara 2017 {published data only}
    1. Vara AD, Koueiter DM, Pinkas DE, Gowda A, Wiater BP, Wiater JM. Intravenous tranexamic acid reduces total blood loss in reverse total shoulder arthroplasty: a prospective, double-blinded, randomized, controlled trial. Journal of Shoulder & Elbow Surgery 2017;26(8):1383-9. [DOI: ] - PubMed
Vles 2020 {published data only}
    1. Vles GF, Corten K, Driesen R, Van 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;105:267-73. [DOI: ] - 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. [DOI: ] - PubMed
Wang 2019 {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 & Haemostasis 2019;119(1):92-103. [DOI: ] - PubMed
Watts 2017 {published data only}
    1. Watts C, Houdek M, Sems S, Cross W, Pagnano M. Tranexamic acid safely reduced blood loss in hip arthroplasty for acute femoral neck fracture. In: OTA annual meeting. 2016:164-5. - PubMed
    1. Watts CD, Houdek MT, Sems SA, Cross WW, Pagnano MW. Tranexamic acid safely reduced blood loss in hemi- and total hip arthroplasty for acute femoral neck fracture: a randomized clinical trial. Journal of Orthopaedic Trauma 2017;31(7):345-51. [DOI: ] - 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. [DOI: ] - PubMed
Wendt 1982 {published data only}
    1. Wendt P, Ketterl R, Haas S, Fritsche HM, Kienzle H, Lechner F, et al. Postoperative increase in lactate in total hip endoprosthesis operations. Effect of aprotinin. Results of a clinical double-blind study. Medizinische Welt 1982;33(13):475-9. - PubMed
Xie 2016 {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. [DOI: ] [PMID: ] - 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. [DOI: 10.1007/s00264-003-0511-4] [PMID: ] - DOI - PMC - PubMed
Yee 2022 {published data only}
    1. NCT04290884. Tranexamic acid in Chinese elderly patients with intertrochanteric fracture RCT. https://www.clinicaltrials.gov/ct2/show/study/NCT04290884 First posted: 2 March 2020 (retrospective).
    1. Yee DK, Wong JS, Fang E, Wong TM, Fang C, Leung F. Topical administration of tranexamic acid in elderly patients undergoing short femoral nailing for intertrochanteric fracture: a randomised controlled trial. Injury 2022;53(2):603-9. [DOI: ] - PubMed
Yu 2020 {published data only}
    1. Yu D, Hu S, Yang X, Zou Y, Chen Y, Hu B, et al. Tranexamic acid controls postoperative hidden blood loss in senile intertrochanteric fracture. [Chinese]. Chinese Journal of Tissue Engineering Research 2020;24(21):23353-7. [DOI: ]
Zhao 2016 {published data only}
    1. Zhao QB, Ren JD, Zhang XG, Wu HZ, Wu L. 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):459-63. [DOI: ]
Zhou 2019 {published data only}
    1. Zhou XD, Zhang Y, Jiang LF, Zhang JJ, Zhou D, Wu LD, et al. Efficacy and safety of tranexamic acid in intertrochanteric fractures: a single-blind randomized controlled trial. Orthopaedic Audio-Synopsis Continuing Medical Education [Sound Recording] 2019;11(4):635-42. [DOI: ] - PMC - PubMed
Zufferey 2010 {published data only}
    1. NCT00327106. Tranexamic acid in hIp fracture surgery (THIF Study) (THIF). https://clinicaltrials.gov/ct2/show/study/NCT00327106 First posted: 18 May 2006 (retrospective).
    1. Zufferey PJ, Miquet M, Quenet S, Laporte S, Martin P, Chambefort V, et al. Does tranexamic acid decrease erythrocyte transfusion in patients undergoing hip fracture surgery with fondaaparinux for prevention of venous thromboembolism? In: Journal of Thrombosis and Haemostasis : JTH. Vol. Suppl 2. 2007:Poster P-M-244. [DOI: ]
    1. Zufferey PJ, Miquet M, Quenet S, Martin P, Adam P, Albaladejo P, et al. Tranexamic acid in hip fracture surgery: a randomized controlled trial. British Journal of Anaesthesia 2010;104(1):23-30. [DOI: ] - PubMed

References to studies awaiting assessment

Akram 2021 {published data only}
    1. Akram M, Muqadas A, Mahmood A, Farooqi FM, Jabbar S. Reduction in blood loss with tranexamic acid use in dynamic hip screw surgery for intertrochanteric fractures. Pakistan Journal of Medical and Health Sciences 2021;15(7):1657-60. [DOI: ]
Chen 2019 {published data only}
    1. Chen F, Jiang Z, Li M, Zhu X. Efficacy and safety of perioperative tranexamic acid in elderly patients undergoing trochanteric fracture surgery: a randomised controlled trial. Hong Kong Medical Journal 2019;25(2):120-6. [DOI: ] - PubMed
ChiCTR 1800015265 {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. http://www.chictr.org.cn/showprojen.aspx?proj=26034 Date of registration：2018-03-19 (prospective). - PubMed
ChiCTR‐IPR‐17011260 {published data only}
    1. ChiCTR-IPR-17011260 . Efficacy and safety of intravenous administration of tranexamic acid for hemostasis in elder patients undergoing PFNA operation for intertrochanteric fracture. http://www.chictr.org.cn/showprojen.aspx?proj=17381 Date of registration: 2017-04-28 (prospective).
CTRI/2018/02/012030 {published data only}
    1. CTRI/2018/02/012030. Comparison of efficacy of intravenous versus topical tranexamic acid in total hip replacement [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]. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=23219 Date of registration: 21-02-2018 (prospective).
Drakos 2016 {published data only}
    1. Drakos A, Raoulis V, Karatzios K, Doxariotis N, Kontogeorgakos V, Malizos K, et al. Efficacy of local administration of tranexamic acid for blood salvage in patients undergoing intertrochanteric fracture surgery. Journal of Orthopaedic Trauma 2016;30(8):409-14. [DOI: ] - PubMed
Emara 2014 {published data only}
    1. Emara WM, Moez KK, Elkhouly AH. Topical versus intravenous tranexamic acid as a blood conservation intervention for reduction of post-operative bleeding in hemiarthroplasty. Anesthesia Essays and Researches 2014;8(1):48-53. [DOI: ] [PMID: ] - PMC - PubMed
Kazemi 2010 {published data only}
    1. Kazemi SM, Mosaffa F, Eajazi A, Kaffashi M, Besheli LD, Bigdeli MR, et al. Hip the effect of tranexamic acid on reducing blood loss in cementless total hip arthroplasty under epidural anesthesia. Orthopedics 2010;33(1):17-22. [DOI: ] [PMID: ] - PubMed
Li 2021 {published data only}
    1. Li H, Liu D, Tang X, Wang N, Gong D, Wu Y, et al. Efficacy and safety of intravenous combined with topical administration of tranexamic acid in reducing blood loss after intramedullary fixation of intertrochanteric femoral fractures. Chinese Journal of Reparative and Reconstructive Surgery 2021;35(5):550-5. [DOI: ] - PMC - PubMed
Lin 2021 {published data only}
    1. Lin JA, Cui HD, Hong Y, Lyu SJ. Application of tranexamic acid in the treatment of intertrochanteric fracture of femur. Zhongguo Gushang 2021;34(7):601-4. [DOI: ] - PubMed
Liu 2022 {published data only}
    1. Liu J, Lei Y, Liao J, Liang X, Hu N, Huang W. Pre-emptive antifibrinolysis: its role and efficacy in hip fracture patients undergoing total hip arthroplasty. Journal of Arthroplasty 2022;37(4):755-62. [DOI: ] - PubMed
Luo 2018 {published data only}
    1. Luo GG, Lin ZQ, Xie HF, Yao JC, Zhang HZ. Preliminary analysis of the effect of different administration routes of tranexamic acid on blood loss after total hip arthroplasty for female femur neck fractures. Zhongguo Gushang 2018;31(12):1086-90. [DOI: ] [PMID: ] - PubMed
Moghaddam 2009 {published data only}
    1. Moghaddam MJ, Darabi E, Sheikholeslamy F. Effect of tranexamic acid in decreasing need to transfusion in hip fracture surgery. In: European Journal of Anaesthesiology. Vol. 48. 2011:89 (Abstract no. 6AP4-5). [URL: https://journals.lww.com/ejanaesthesiology/Citation/2011/06001/Effect_of...]
    1. Moghaddam MJ, Razavi SS, Momenzadeh S, Radfar A. The effects of tranexamic acid on hemorrhage in femoral fracture surgery. Research in Medicine: Journal of Research in Medical Sciences 2009;33(2):3.
Mohib 2015 {published data only}
    1. Mohib Y, Rashid RH, Ali M, Zubairi AJ, Umer M. Does tranexamic acid reduce blood transfusion following surgery for inter-trochanteric fracture? A randomized control trial. JPMA - Journal of the Pakistan Medical Associatio 2015;65(11 Suppl 3):s17-s20. - PubMed
NCT01683955 {published data only}
    1. NCT01683955. Topical tranexamic acid and acute blood loss in total hip arthroplasty. https://clinicaltrials.gov/ct2/show/study/NCT01683955 First posted: 12 September 2012 (prospective).
NCT02094066 {published data only}
    1. NCT02094066. The effect of tranexamic acid for total hip arthroplasty. https://clinicaltrials.gov/ct2/show/study/NCT02094066 First posted: 21 March 2014 (prospective).
NCT02438566 {published data only}
    1. NCT02438566. Non-inferiority trial of oral tranexamic acid vs. intravenous tranexamic acid in joint replacement surgery. https://clinicaltrials.gov/ct2/show/study/NCT02438566 First posted: 8 May 2015 (retrospective).
NCT02738073 {published data only}
    1. NCT02738073. Effects of tranexamic acid on blood loss and transfusion requirement following hip fracture. https://clinicaltrials.gov/ct2/show/study/NCT02738073 First posted: 14 April 2016 (start date NR).
NCT03157401 {published data only}
    1. NCT03157401. Two different administration methods of tranexamic acid on perioperative blood loss during total hip arthroplasty. https://clinicaltrials.gov/ct2/show/record/NCT03157401?view=record First posted: 17 May 2017 (retrospective).
NCT03822793 {published data only}
    1. NCT03822793. A dose-response study of tranexamic acid in total hip arthroplasty (PRADO). https://clinicaltrials.gov/ct2/show/study/NCT03822793 First posted: 30 January 2019 (prospective).
NCT03897621 {published data only}
    1. NCT03897621. The effect of tranexamic acid on blood coagulation in total hip arthroplasty surgery. https://clinicaltrials.gov/ct2/show/study/NCT03897621 First posted: 1 April 2019 (prospective).
NCT04089865 {published data only}
    1. NCT04089865. Oral versus IV TXA. https://clinicaltrials.gov/ct2/show/study/NCT04089865 First posted: 13 September 2019 (prospective).
NCT04187014 {published data only}
    1. NCT04187014. Oral tranexamic acid vs. oral aminocaproic acid to reduce blood loss after total hip replacement. https://clinicaltrials.gov/ct2/show/study/NCT04187014 First posted: 5 December 2019 (prospective).
Notarfrancesco 2015 {published data only}
    1. Notarfrancesco D, Zara A, Lamberti A, Aquino F, Russo L. Intra-articular and intravenous tranexamic acid to reduce blood loss in total hip replacement. HIP International 2015;1:s96. [DOI: ]
Sahni 2021 {published data only}
    1. R Champaneria. Personal email to Dr Sanjeev Kumar Arora to ask for a trial registration number Email sent on 25 May 2022.
    1. Sahni G, Sood M, Girdhar D, Sahni P, Jain AK, Kumar S. To analyze the role of intravenous tranexamic acid in hip fracture surgeries in orthopedic trauma. International Journal of Applied and Basic Medical Research 2021;11(3):139-42. [DOI: ] - PMC - PubMed
Singh 2020 {published data only}
    1. Singh M, Ummat A, Verma V, Thivari P, Kaur H. Role of tranexamic acid in controlling blood loss in major orthopaedic surgeries (TRAMOS): a comparative study. Indian Journal of Public Health Research and Development 2020;11(2):808-12. [DOI: ]
Spitler 2019 {published data only}
    1. Spitler CA, Kiner DW, Row ER, Gardner WE, Swafford RE, Hankins MJ, et al. Tranexamic acid use in open reduction and internal fixation of fractures of the pelvis, acetabulum, and proximal femur: a randomized controlled trial. Journal of Orthopaedic Trauma 2019;33(8):371-76. [DOI: ] - PubMed
Taheriazam 2015 {published data only}
    1. Taheriazam A, Safdari F. Using tranexamic acid to decrease postoperative hemorrhage: local versus intravenous administration. HIP International 2015;1:s90. [DOI: ]
Taheriazam 2016 {published data only}
    1. Taheriazam A Safdari F. Using tranexamic acid to decrease postoperative hemorrhage: local versus intravenous administration. HIP International 2016;26 Suppl 2:s41 (Presentation OP16-102). [DOI: ]
Tian 2018 {published data only}
    1. Tian S, Shen Z, Liu Y, Zhang Y, Peng A. The effect of tranexamic acid on hidden bleeding in older intertrochanteric fracture patients treated with PFNA. Injury 2018;49(3):680-4. [DOI: ] - PubMed
Vijay 2013 {published data only}
    1. Vijay BS, Bedi V, Mitra S, Das B. Role of tranexamic acid in reducing postoperative blood loss and transfusion requirement in patients undergoing hip and femoral surgeries. Saudi Journal of Anaesthesia 2013;7(1):29-32. [DOI: ] - PMC - PubMed
Wang 2021 {published data only}
    1. Wang H, Lu Z, Li T, Wang S, Wang Y. Effect of repeated intravenous tranexamic acid in the perioperative period of proximal femoral nail antirotation for femoral intertrochanteric fracture. Chinese Journal of Tissue Engineering Research 2021;25(21):3319-23. [DOI: ]
Wu 2016 {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. [DOI: ] - PubMed
Yang 2020 {published data only}
    1. Yang YY Qin H Zheng X Hu B Zhang M Ma T. Administration of tranexamic acid in proximal humeral fractures. Indian Journal of Orthopaedics 2020;54 Suppl 2:277-82. [DOI: ] - PMC - PubMed
Zhang 2019 {published data only}
    1. Zhang R, Yang Z, Lei T, Ping Z, Bai G. Effects of aminocaproic acid on perioperative hidden blood loss in elderly patients with femoral intertrochanteric fracture treated with proximal femoral nail anti-rotation. Journal of International Medical Research 2019;47(10):5010-8. [DOI: ] [PMID: ] - PMC - PubMed
Zhang 2020b {published data only}
    1. Zhang Q, Xiang C, Chen X, Chen L, Chen Q, Jiang K, et al. Application of intravenous injection of tranexamic acid combined with local use of tranexamic acid cocktail in intertrochanteric fracture fixation. Chinese Journal of Reparative and Reconstructive Surgery 2020;34(4):463-8. [DOI: ] - PMC - PubMed
Zheng 2020 {published data only}
    1. Zheng Z, Chen S, Guan K, Zheng X, Chen H, Zeng Q. Relationship between blood loss of proximal femoral nail anti-rotation fixation and local use combined with intravenous injection of tranexamic acid. Chinese Journal of Tissue Engineering Research 2020;24(9):1359-64. [DOI: ]

References to ongoing studies

ACTRN 12617000391370 {published data only}
    1. ACTRN12617000391370. Role of tranexamic acid on blood loss in hip fracture patients [Role of tranexamic acid on post operative blood loss and blood transfusion in intra capsular neck of femur fracture patients undergoing hip arthroplasty (total hip arthroplasty or hemiarthroplasty)]. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371783&... (first received 16 March 2017).
    1. Champaneria R. Update on the status of your trial [personal communication]. Email to: Dr Yasser Khatib 26 May 2022.
ACTRN 12620001059954 {published data only}
    1. ACTRN12620001059954. Efficacy of perioperative tranexamic acid in patients undergoing trochanteric hip fracture surgery: a randomized placebo controlled trial. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620001... (first received 16 October 2020).
ChiCTR 1800014309 {published data only}
    1. ChiCTR1800014309. Evaluation of topical use of tranexamic acid in reducing hidden blood loss during surgical treatment of intertrochanteric fracture in the elderly. https://trialsearch.who.int/?TrialID=ChiCTR1800014309 (first received 5 January 2018).
    1. ChiCTR1800014309. Evaluation of topical use of tranexamic acid in reducing hidden blood loss during surgical treatment of intertrochanteric fracture in the elderly. https://www.chictr.org.cn/showprojen.aspx?proj=24467 (first received 5 January 2018).
ChiCTR 1800015809 {published data only}
    1. ChiCTR1800015809. Tranexamic acid reduces blood loss in patients with fractures of the hip: a randomized control trial . http://www.chictr.org.cn/showproj.aspx?proj=21913 (first received 22 April 2018).
ChiCTR 1800018334 {published data only}
    1. ChiCTR1800018334. The efficacy and safety of tranexamic acid in perioperation of pelvic and randomized acetabular surgery: a prospective controlled trial. http://www.chictr.org.cn/showproj.aspx?proj=30973 (first received 12 September 2018).
ChiCTR 1900021948 {published data only}
    1. ChiCTR1900021948. Application of combined tranexamic acid and intravenous iron in hip fracture surgery: a randomized controlled trial. http://www.chictr.org.cn/com/25/showprojen.aspx?proj=36971 (first received 17 March 2019).
ChiCTR 2000032758 {published data only}
    1. ChiCTR2000032758. Identifying the optimal regimen for intravenous tranexamic acid administration in hip fractrues: a prospective, randomized, double-blind, controlled study. http://www.chictr.org.cn/showproj.aspx?proj=53328 (first received 9 May 2020).
    1. ChiCTR2000032758. Identifying the optimal regimen for intravenous tranexamic acid administration in hip fractrues: a prospective, randomized, double-blind, controlled study. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2000032758 (first received 9 May 2020).
ChiCTR‐ICC‐15006070 {published data only}
    1. ChiCTR-ICC-15006070. Efficacy and safety of tranexamic acid in pelvic fracture surgery. http://www.chictr.org.cn/showproj.aspx?proj=10545 (first received 13 March 2015).
ChiCTR‐IPR‐17013477 {published data only}
    1. ChiCTR-IPR-17013477. The influence on blood loss and coagulation fucton of different administration methods of tranexamic acid in major orthopedic surgery: a prospective and randomized controlled study. http://www.chictr.org.cn/showproj.aspx?proj=23084 (first received 21 November 2017).
CTRI/2019/04/018735 {published data only}
    1. CTRI/2019/04/018735. Study on how Different Doses of Tranexamic Acid effect the blood loss in Pelviacetabular Fracture Surgery: A Randomized Clinical Trial [Effect of Different Dose Regimens of Tranexamic Acid on blood loss in Pelviacetabular Fracture Surgery: A Randomized Clinical Trial ]. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=31439 (first received 24 April 2019).
    1. Champaneria R. Update on the status of your trial [personal communication]. Email to: Dr Vinay Gandhi and Dr Chhavi Sawhney 24 May 2021.
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 [Perioperative tranexamic acid for the control of bleeding during major orthopedic surgeries in tertiary care hospital]. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=26588 (first received 18 September 2019).
    1. CTRI/2019/09/021302. To use a drug tranexamic acid to reduce blood loss during femur and hip surgeries [Perioperative Tranexamic acid for the control of bleeding during major Orthopedic surgeries in tertiary care hospital.]. https://trialsearch.who.int/?TrialID=CTRI/2019/09/021302 (first received 18 September 2019).
    1. Champaneria R. Update on the status of your trial [personal communication]. Email to: Dr Rajshree Mandhare 13 October 2021.
CTRI/2019/10/021667 {published data only}
    1. CTRI/2019/10/021667. Role of tranexamic acid in reducing blood loss in hip fracture surgeries [Intravenous administration versus local infiltration of tranexamic acid in patients undergoing internal fixation for intertrochanteric fractures – a randomized, prospective, double blind, superiority trial]. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=37338 (first received 16 October 2019).
    1. CTRI/2019/10/021667. Role of tranexamic acid in reducing blood loss in hip fracture surgeries [Intravenous administration versus local infiltration of tranexamic acid in patients undergoing internal fixation for intertrochanteric fractures. A randomized, prospective, double blind, superiority trial]. https://trialsearch.who.int/?TrialID=CTRI/2019/10/021667 (first received 16 October 2019).
    1. Champaneria R. Update on the status of your trial [personal communication]. Email to: Dr Koushik Subramanyam 13 October 2021.
CTRI/2021/09/036855 {published data only}
    1. CTRI/2021/09/036855. Evaluation of efficacy of tranexamic acid on blood loss in periarticular hip surgeries [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]. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=60861 (first received 27 September 2021).
    1. Champaneria R. Update on the status of your trial and clarification on the breakdown of the population please [personal communication]. Email to: Dr Gupta and Dr Mukherjee 25 May 2022.
EUCTR 2011‐006278‐15 {published data only}
    1. EUCTR 2011-006278-15. Prevention of postoperative bleeding: a multicenter, randomized, parallel, controlled clinical trial, evaluating the efficacy of tranexamic acid and fibrin glue in patients undergoing interventions for sub-capital femoral fracture [Prevencion del sangrado postoperatorio: Ensayo clinico, multicéntrico, aleatorizado, controlado, paralelo, que evalua la eficacia del ácido tranexámico y la cola de fibrina fracturas subcapitales de femur.]. https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-006278-15/ES#E (first received 28 February 2012).
EUCTR 2018‐000528‐32 {published data only}
    1. EUCTR 2018-000528-32. Tranexamic acid use to reduce de blood transfusion in femur fracture patients. Clinical randomized trial with placebo control [Utilidad del ácido tranexámico para disminuir las necesidades transfusionales en fractura de fémur. Ensayo clínico aleatorizado controlado con placebo]. https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000528-32/ES (first received 20 April 2018).
IRCT 2017 1030037093N18 {published data only}
    1. IRCT20171030037093N18. Effect of tranexamic acid on blood loss and transfusion in femoral fixation surgeries. http://en.irct.ir/trial/41976 (first received 14 September 2019).
    1. IRCT20171030037093N18. Effect of tranexamic acid on blood loss and transfusion in femoral fixation surgeries. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20171030037093N18 (first received 14 September 2019).
IRCT 2020 0109046064N1 {published data only}
    1. IRCT20200109046064N1. Effect of fibrinogen on bleeding during pelvic surgery [The effect of prophylactic fibrinogen infusion on intraoperative bleeding during pelvic surgery]. http://en.irct.ir/trial/44925 (first received 11 February 2020).
    1. IRCT20200109046064N1. Effect of fibrinogen on bleeding during pelvic surgery [The effect of prophylactic fibrinogen infusion on intraoperative bleeding during pelvic surgery]. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20200109046064N1 (first received 11 February 2020).
Liu 2021 {published data only}
    1. ChiCTR2100045960. Hemostatic efficacy and safety of preemptive antifibrinolysis with multi-dose intravenous tranexamic acid in elderly hip fracture patients: a prospective randomized controlled trial. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2100045960 (first received 30 April 2021). - PMC - PubMed
    1. ChiCTR2100045960. Hemostatic efficacy and safety of preemptive antifibrinolysis with multi-dose tranexamic acid in elderly hip fracture patients: a prospective randomized intravenous controlled trial. chictr.org.cn/showproj.aspx?proj=125983 (first received 30 April 2021).
    1. Liu J, Lei Y, Liao J, Liang X, Hu N, Huang W. Study protocol: haemostatic efficacy and safety of preemptive antifibrinolysis with multidose intravenous tranexamic acid in elderly hip fracture patients: design of a prospective randomised controlled trial. BMJ Open 2021;11(12):e047382. [DOI: ] - PMC - PubMed
NCT02428868 {published data only}
    1. NCT02428868. IV iron in association with tranexamic acid for hip fracture [Use of combined tranexamic acid and intravenous iron for hip fracture surgery in elderly]. clinicaltrials.gov/ct2/show/NCT02428868 (first received 29 April 2015).
NCT02938962 {published data only}
    1. NCT02938962. Intravenous vs. topical tranexamic acid in revision THA (VITALITY-X) (VITALITY-X) [Revision Total Hip Arthroplasty: Comparison of the Effects of Intravenous and Topically Administered Tranexamic Acid in a Prospective Randomized Trial (VITALITY-X)]. clinicaltrials.gov/ct2/show/NCT02938962 (first received 19 October 2016).
NCT02972294 (HiFIT) {published data only}
    1. EudraCT 2016-003087-40. Interest of intraveinous iron and tranexamic acid to reduce transfusion in hip fracture patients - HIFIT study. clinicaltrialsregister.eu/ctr-search/trial/2016-003087-40/FR (first received 04 April 2016).
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NCT03063892 {published data only}
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NCT03182751 {published data only}
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NCT03211286 {published data only}
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NCT03923959 {published data only}
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TCTR 2021 0311001 {published data only}
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TCTR 2021 0316006 {published data only}
    1. TCTR20210316006. Tranexamic acid in displaced femoral neck fracture treated with bipolar hemiarthroplasty: a randomized, controlled trial of topical versus intravenous administration. https://www.thaiclinicaltrials.org/show/TCTR20210316006 (first received 16 March 2021).

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