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Meta-Analysis
. 2024 Jan 8;1(1):CD011858.
doi: 10.1002/14651858.CD011858.pub2.

Anticoagulation for people receiving long-term haemodialysis

Patrizia Natale  1   2   3 , Suetonia C Palmer  4 , Marinella Ruospo  3 , Henrietta Longmuir  5 , Benjamin Dodds  5 , Ritam Prasad  6 , Tracey J Batt  7 , Matthew D Jose  5 , Giovanni Fm Strippoli  1   3   8
Affiliations
Meta-Analysis

Anticoagulation for people receiving long-term haemodialysis

Patrizia Natale et al. Cochrane Database Syst Rev. .

Abstract

Background: Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding.

Objectives: To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to November 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating anticoagulant agents administered during HD treatment in adults and children with kidney failure.

Data collection and analysis: Two authors independently assessed the risk of bias using the Cochrane tool and extracted data. Treatment effects were estimated using random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE).

Main results: We included 113 studies randomising 4535 participants. The risk of bias in each study was adjudicated as high or unclear for most risk domains. Compared to UFH, LMWH had uncertain effects on extracorporeal circuit thrombosis (3 studies, 91 participants: RR 1.58, 95% CI 0.46 to 5.42; I2 = 8%; low certainty evidence), while major bleeding and minor bleeding were not adequately reported. Regional citrate anticoagulation may lower the risk of minor bleeding compared to UFH (2 studies, 82 participants: RR 0.34, 95% CI 0.14 to 0.85; I2 = 0%; low certainty evidence). No studies reported data comparing regional citrate to UFH on risks of extracorporeal circuit thrombosis and major bleeding. The effects of very LMWH, danaparoid, prostacyclin, direct thrombin inhibitors, factor XI inhibitors or heparin-grafted membranes were uncertain due to insufficient data. The effects of different LMWH, different doses of LMWH, and the administration of LMWH anticoagulants using inlet versus outlet bloodline or bolus versus infusion were uncertain. Evidence to compare citrate to another citrate or control was scant. The effects of UFH compared to no anticoagulant therapy or different doses of UFH were uncertain. Death, dialysis vascular access outcomes, blood transfusions, measures of anticoagulation effect, and costs of interventions were rarely reported. No studies evaluated the effects of treatment on non-fatal myocardial infarction, non-fatal stroke and hospital admissions. Adverse events were inconsistently and rarely reported.

Authors' conclusions: Anticoagulant strategies, including UFH and LMWH, have uncertain comparative risks on extracorporeal circuit thrombosis, while major bleeding and minor bleeding were not adequately reported. Regional citrate may decrease minor bleeding, but the effects on major bleeding and extracorporeal circuit thrombosis were not reported. Evidence supporting clinical decision-making for different forms of anticoagulant strategies for HD is of low and very low certainty, as available studies have not been designed to measure treatment effects on important clinical outcomes.

Trial registration: ClinicalTrials.gov NCT03319680 NCT00669721 NCT02281045 NCT02553889 NCT00756145 NCT00395824 NCT03887468 NCT03090984 NCT00473109 NCT01930396 NCT01318486 NCT03419923 NCT03612856 NCT04381234 NCT01466959 NCT03820401 NCT02957877 NCT00407641 nct00260988 NCT03799822 NCT02610933 NCT01356615 NCT05679024 NCT05705076 NCT05874674.

PubMed Disclaimer

Conflict of interest statement

  1. Patrizia Natale: no relevant interests were disclosed

  2. Suetonia C Palmer: no relevant interests were disclosed

  3. Marinella Ruospo: no relevant interests were disclosed

  4. Henrietta Longmuir: no relevant interests were disclosed

  5. Benjamin Dodds: no relevant interests were disclosed

  6. Luke Bereznicki: no relevant interests were disclosed

  7. Ritam Prasad: no relevant interests were disclosed

  8. Tracey Batt: Novo Nordisk (Independent Contractor ‐ Other)

  9. Matthew D Jose: no relevant interests were disclosed

  10. Giovanni FM Strippoli: no relevant interests were disclosed

Figures

1
1
Study selection flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Unfractionated heparin (UFH) versus no anticoagulation, Outcome 1: Extracorporeal circuit thrombosis
1.2
1.2. Analysis
Comparison 1: Unfractionated heparin (UFH) versus no anticoagulation, Outcome 2: Activated partial thromboplastin time
1.3
1.3. Analysis
Comparison 1: Unfractionated heparin (UFH) versus no anticoagulation, Outcome 3: Platelet count
2.1
2.1. Analysis
Comparison 2: Low molecular weight heparin (LMWH) versus no anticoagulation, Outcome 1: Extracorporeal circuit thrombosis
2.2
2.2. Analysis
Comparison 2: Low molecular weight heparin (LMWH) versus no anticoagulation, Outcome 2: Activated partial thromboplastin time
2.3
2.3. Analysis
Comparison 2: Low molecular weight heparin (LMWH) versus no anticoagulation, Outcome 3: Platelet count
3.1
3.1. Analysis
Comparison 3: Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 1: Extracorporeal circuit thrombosis
3.2
3.2. Analysis
Comparison 3: Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 2: Dialysis vascular access thrombosis
3.3
3.3. Analysis
Comparison 3: Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 3: Dialysis adequacy (Kt/V)
3.4
3.4. Analysis
Comparison 3: Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 4: Death (any cause)
3.5
3.5. Analysis
Comparison 3: Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 5: Plasma anti‐Xa level
3.6
3.6. Analysis
Comparison 3: Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 6: Activated partial thromboplastin time
3.7
3.7. Analysis
Comparison 3: Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 7: Platelet count
3.8
3.8. Analysis
Comparison 3: Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 8: Potassium
4.1
4.1. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 1: Extracorporeal circuit thrombosis
4.2
4.2. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 2: Major bleeding
4.3
4.3. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 3: Minor bleeding
4.4
4.4. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 4: Subcutaneous bleeding
4.5
4.5. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 5: Subconjunctival bleeding
4.6
4.6. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 6: Haemorrhoid bleeding
4.7
4.7. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 7: Vascular access bleeding
4.8
4.8. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 8: Death (any cause)
4.9
4.9. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 9: Plasma anti‐Xa level
4.10
4.10. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 10: Activated clotting time
4.11
4.11. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 11: Thrombin antithrombin complex
4.12
4.12. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 12: Thrombin time
4.13
4.13. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 13: Prothrombin time
4.14
4.14. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 14: Activated partial thromboplastin time
4.15
4.15. Analysis
Comparison 4: Low molecular weight heparin (LMWH) versus other LMWH, Outcome 15: Time to stop bleeding
5.1
5.1. Analysis
Comparison 5: Low molecular weight heparin (LMWH) versus danaparoid, Outcome 1: Dialysis access (urea reduction ratio)
5.2
5.2. Analysis
Comparison 5: Low molecular weight heparin (LMWH) versus danaparoid, Outcome 2: Plasma anti‐Xa level
6.1
6.1. Analysis
Comparison 6: Low molecular weight heparin (LMWH) versus fixed‐dose LMWH, Outcome 1: Extracorporeal circuit thrombosis (clotting bloodlines)
6.2
6.2. Analysis
Comparison 6: Low molecular weight heparin (LMWH) versus fixed‐dose LMWH, Outcome 2: Any bleeding
7.1
7.1. Analysis
Comparison 7: High versus low‐dose low molecular weight heparin (LMWH), Outcome 1: Plasma anti‐Xa level
8.1
8.1. Analysis
Comparison 8: Very low molecular weight heparin (VLMWH) versus no heparin, Outcome 1: Extracorporeal circuit thrombosis
8.2
8.2. Analysis
Comparison 8: Very low molecular weight heparin (VLMWH) versus no heparin, Outcome 2: Worsening haemorrhage
9.1
9.1. Analysis
Comparison 9: Prostacyclin versus unfractionated heparin (UFH), Outcome 1: Potassium
10.1
10.1. Analysis
Comparison 10: Direct thrombin inhibitor (DTI) versus unfractionated heparin (UFH), Outcome 1: Minor bleeding
11.1
11.1. Analysis
Comparison 11: Citrate versus unfractionated heparin (UFH), Outcome 1: Extracorporeal circuit thrombosis
11.2
11.2. Analysis
Comparison 11: Citrate versus unfractionated heparin (UFH), Outcome 2: Any bleeding
11.3
11.3. Analysis
Comparison 11: Citrate versus unfractionated heparin (UFH), Outcome 3: Minor bleeding
12.1
12.1. Analysis
Comparison 12: Citrate + Evodial versus citrate, Outcome 1: Extracorporeal circuit thrombosis
13.1
13.1. Analysis
Comparison 13: Continuous versus two‐stage citrate infusion, Outcome 1: Extracorporeal circuit thrombosis
13.2
13.2. Analysis
Comparison 13: Continuous versus two‐stage citrate infusion, Outcome 2: Cardiovascular adverse events
14.1
14.1. Analysis
Comparison 14: Citrate versus control, Outcome 1: Extracorporeal circuit thrombosis
14.2
14.2. Analysis
Comparison 14: Citrate versus control, Outcome 2: Cardiovascular adverse events
15.1
15.1. Analysis
Comparison 15: Modified versus simplified citrate, Outcome 1: Cost per treatment
16.1
16.1. Analysis
Comparison 16: Sequential anticoagulation versus citrate, Outcome 1: Extracorporeal circuit thrombosis
17.1
17.1. Analysis
Comparison 17: Factor XI inhibitor versus placebo, Outcome 1: Major bleeding
17.2
17.2. Analysis
Comparison 17: Factor XI inhibitor versus placebo, Outcome 2: Any bleeding
17.3
17.3. Analysis
Comparison 17: Factor XI inhibitor versus placebo, Outcome 3: Minor bleeding
17.4
17.4. Analysis
Comparison 17: Factor XI inhibitor versus placebo, Outcome 4: Death (any cause)
17.5
17.5. Analysis
Comparison 17: Factor XI inhibitor versus placebo, Outcome 5: Cardiovascular death
17.6
17.6. Analysis
Comparison 17: Factor XI inhibitor versus placebo, Outcome 6: Blood transfusion
18.1
18.1. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 1: Extracorporeal circuit thrombosis
18.2
18.2. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 2: Clotting leading to discontinuation
18.3
18.3. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 3: Gastrointestinal bleeding
18.4
18.4. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 4: Cerebral haemorrhage
18.5
18.5. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 5: Vascular access site haemorrhage
18.6
18.6. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 6: Vascular access thrombosis
18.7
18.7. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 7: Vascular access site haematoma
18.8
18.8. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 8: Vascular access complication
18.9
18.9. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 9: Cardiovascular death
18.10
18.10. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 10: Cardiorespiratory arrest
18.11
18.11. Analysis
Comparison 18: Heparin‐grafted membrane versus saline flushes, Outcome 11: Pain
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD011858

References

References to studies included in this review

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Ezzatzadegan 2011 {published data only}
    1. Ezzatzadegan Jahromi S, Roozbeh J, Mahmoodi MS. Comparing the effect of unfractionated heparin with low molecular weight heparin on serum potassium level in hemodialysis patients [abstract no: P412]. Iranian Journal of Kidney Diseases 2011;5(Suppl 2):66. [EMBASE: 70673920] - PubMed
Ezzatzadegan 2014 {published data only}
    1. Ezzatzadegan Jahromi S, Mahmoodi MS, Behroozi F, Roozbeh J, Emamghoreishi F. Effect of switching unfractionated heparin to low-molecular-weight heparin on serum potassium in hemodialysis patients. Iranian Journal of Kidney Diseases 2014;8(6):475-80. [MEDLINE: ] - PubMed
Flanigan 1987 {published data only}
    1. Flanigan MJ, Von Brecht J, Freeman RM, Lim VS. Reducing the hemorrhagic complications of hemodialysis: a controlled comparison of low-dose heparin and citrate anticoagulation. American Journal of Kidney Diseases 1987;9(2):147-53. [MEDLINE: ] - PubMed
Flanigan 1996 {published data only}
    1. Flanigan MJ, Pillsbury L, Sadewasser G, Lim VS. Regional hemodialysis anticoagulation: hypertonic tri-sodium citrate or anticoagulant citrate dextrose-A. American Journal of Kidney Diseases 1996;27(4):519-24. [MEDLINE: ] - PubMed
Franca Gois 2022 {published data only}
    1. Franca Gois P, McIntyre D, Ratanjee S, Pelecanos A, Scuderi C, Janoschka CL, et al. Hemodialysis without systemic anticoagulation: a prospective randomised pilot trial to evaluate five strategies in patients at high risk of bleeding (HepFree Trial) [abstract no: POS-618]. KI Reports 2022;7(2 Suppl):S265. [EMBASE: 2016905686]
Francois 2020 {published data only}
    1. Francois K, Orlando C, Jochmans K, Cools W, De Meyer V, Tielemans C, et al. Hemodialysis does not induce detectable activation of the contact system of coagulation. KI Reports 2020;5(6):831-8. [MEDLINE: ] - PMC - PubMed
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Frei 1988 {published data only}
    1. Frei U, Wilks MF, Boehmer S, Crisp-Lindgren N, Schwarzrock R, Stiekema JC, et al. Gastrointestinal blood loss in haemodialysis patients during use of a low-molecular-weight heparinoid anticoagulant. Nephrology Dialysis Transplantation 1988;3(4):435-9. [MEDLINE: ] - PubMed
Gabutti 2004 {published data only}
    1. Gabutti L, Ferrari N, Mombelli G, Keller F, Marone C. The favorable effect of regional citrate anticoagulation on interleukin-1beta release is dissociated from both coagulation and complement activation. Journal of Nephrology 2004;17(6):819-25. [MEDLINE: ] - PubMed
Gritters 2006 {published data only}
    1. Gritters M, Grooteman MP, Schoorl M, Schoorl M, Bartels PC, Scheffer PG, et al. Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis. Nephrology Dialysis Transplantation 2006;21(1):153-9. [MEDLINE: ] - PubMed
Gritters 2007 {published data only}
    1. Gritters M, Borgdorff P, Grooteman MP, Schoorl M, Schoorl M, Bartels PC, et al. Reduction in platelet activation by citrate anticoagulation does not prevent intradialytic hemodynamic instability. Nephron 2007;106(1):c9-16. [MEDLINE: ] - PubMed
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    1. Guery B, Alberti C, Servais A, Harrami E, Bererhi L, Zins B, et al. Hemodialysis without systemic anticoagulation: a prospective randomized trial to evaluate 3 strategies in patients at risk of bleeding. PLoS ONE [Electronic Resource] 2014;9(5):e97187. [MEDLINE: ] - PMC - PubMed
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HEMO‐TIN 2016 {published data only}
    1. Ribic C, Gangii AS, Moist LM, Walsh M, Cook DJ, Crowther MA. Intermittent HEMOdialysis anticoagulation with TINzaparin versus unfractionated heparin: a pilot multicentre randomized controlled trial (HEMO-TIN Trial) [abstract no: FR-PO1141]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):7B.
    1. Ribic C, Gangji A, Walsh M, Moist L, Cook D, Lim W, et al. Intermittent hemodialysis anticoagulation with tinzaparin versus unfractionated heparin (HEMO-TIN): a multicentre randomized control trial [abstract no: O-002]. In: Canadian Society of Nephrology Annual General Meeting; 2017 May 4-6; Montreal, Canada. 2017:3.
Henny 1985 {published data only}
    1. Henny CP, ten Cate H, Surachno S, Stevens P, Buller HR, den Hartog M, et al. The effectiveness of a low molecular weight heparinoid in chronic intermittent haemodialysis. Thrombosis & Haemostasis 1985;54(2):460-2. [MEDLINE: ] - PubMed
HepZero 2013 {published data only}
    1. Laville M, Dorval M, Fort J, Fay R, Moureau F, Loughraieb N, et al. A randomized controlled multicenter trial of a heparin-grafted polyacrylonitrile membrane for no-heparin hemodialysis versus standard-of-care: results of the HEPZERO study [abstract no: SA-PO1084]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):4B.
    1. Laville M, Dorval M, Fort Ros J, Fay R, Cridlig J, Nortier JL, et al. A randomized controlled multicenter trial of a heparin-grafted polyacrylonitrile membrane for no-heparin hemodialysis versus standard-of-care: results of the HepZero study [abstract no: MO035]. Nephrology Dialysis Transplantation 2014;29(Suppl 2):iii37. [EMBASE: 71491554]
    1. Laville M, Dorval M, Fort Ros J, Fay R, Cridlig J, Nortier JL, et al. Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis. Kidney International 2014;86(6):1260-7. [MEDLINE: ] - PubMed
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Hirasawa 1993 {published data only}
    1. Hirasawa Y, Takahashi S, Ota K, Koide K, Koshikawa S, Mimura N, et al. Clinical evaluation of RPY-005, a low molecular weight heparin, for extracorporeal circulation during hemodialysis in patients with chronic renal insufficiency - a double-blind cross-over comparative study with heparin. Japanese Pharmacology & Therapeutics 1993;21(10):457-98. [EMBASE: 24024344]
Hottelart 1998 {published data only}
    1. Hottelart C, Achard JM, Moriniere P, Zoghbi F, Dieval J, Fournier A. Heparin-induced hyperkalemia in chronic hemodialysis patients: comparison of low molecular weight and unfractionated heparin. Artificial Organs 1998;22(7):614-7. [MEDLINE: ] - PubMed
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    1. Janssen MJ, Beukhof JR, Meulen J, Donker AJ. Citrate (CIT) compared to low molecular weight heparin (LMWH) anticoagulation in chronic haemodialysis (HD) patients [abstract]. Nephrology Dialysis Transplantation 1996;11(6):A203. [CENTRAL: CN-00261287]
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Jiang 1997 {published data only}
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Kanamori 1993 {published data only}
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Klejna 2014 {published data only}
    1. Klejna K, Naumnik B, Koc-Zorawska E, Mysliwiec M. Effect of unfractionated and low-molecular-weight heparin on OPG, sRANKL, and von Willebrand factor concentrations during hemodialysis. Clinical & Applied Thrombosis/Hemostasis 2014;20(4):433-41. [MEDLINE: ] - PubMed
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    1. Klingel R, Gohlke F, Hafner G, Wandel E. Impact of dialyzer membrane and surface area on activation of coagulation and complement during low-dose anticoagulation with low molecular weight heparin (LMWH) for hemodialysis [abstract no: P1341]. Nephrology 1997;3(Suppl 1):S408. [CENTRAL: CN-01658411]
Kodras 2008 {published data only}
    1. Kodras K, Benesch T, Neumann I, Haas M. Comparison of two dialysers (AN69ST vs. FX100) for heparin-free dialysis in patients with oral anticoagulation. Blood Purification 2008;26(3):226-30. [MEDLINE: ] - PubMed
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    1. Koshikawa S, Akizawa T, Mimura N, Ota K, Hirasawa Y, Maekawa M, et al. Effects of LHG-500 (Low Molecular Weight Heparin) as an anticoagulant for hemodialysis patients with bleeding risks. Multi-institutional control study with low dose or regional heparinization. Rinsho Hyoka 1991;19:541-71. [CENTRAL: CN-00256286]
Koshikawa 1991a {published data only}
    1. Koshikawa S, Akizawa T, Mimura N, Ota K, Hirasawa Y, Mackawa M, et al. Effects of single bolus injection of low molecular weight heparin (LHG-500) as an anticoagulant for hemodialysis. Double-blind cross-over study in comparison with continuous administration of conventional heparin. Rinsho Hyoka 1991;19:491-540. [CENTRAL: CN-00601678]
Kurtkoti 2016 {published data only}
    1. Kurtkoti J, Bose B, Hiremagalur B, Sun J, Cochrane T. Arterial line versus venous line administration of low molecular weight heparin, enoxaparin for prevention of thrombosis in the extracorporeal blood circuit of patients on haemodialysis or haemodiafiltration-a randomized cross-over trial [abstract no: FP535]. Nephrology Dialysis Transplantation 2015;30(Suppl 3):iii251. [EMBASE: 72206955] - PubMed
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Lebon 1995 {published data only}
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Leitienne 2000 {published data only}
    1. Leitienne P, Fouque D, Rigal D, Adeleine P, Trzeciak MC, Laville M. Heparins and blood polymorphonuclear stimulation in haemodialysis: an expansion of the biocompatibility concept. Nephrology Dialysis Transplantation 2000;15(10):1631-7. [MEDLINE: ] - PubMed
Lim 2018 {published data only}69952745
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Lin 2019a {published data only}GDREC2017250H
    1. Lin T, Song L, Huang R, Huang Y, Tang S, Lin Q, et al. Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies. BMC Nephrology 2019;20(1):472. [MEDLINE: ] - PMC - PubMed
Lin 2019b {published data only}GDREC2017250H
    1. Lin T, Song L, Huang R, Huang Y, Tang S, Lin Q, et al. Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies. BMC Nephrology 2019;20(1):472. [MEDLINE: ] - PMC - PubMed
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Lorentz 2021 {published data only}
    1. Lorentz CU, Tucker EI, Verbout NG, Shatzel JJ, Olson SR, Markway BD, et al. The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial. Blood 2021;138(22):2173-84. [PMID: ] - PMC - PubMed
Luo 2021 {published data only}
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Mahmood 2010 {published data only}
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Moia 1997 {published data only}
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    1. Moriniere P, Maret J, Debure A, Lebon P, Dion JJ, Bayrou B, et al. Thrombosis prevention during hemodialysis of patients with high hemorrhagic risk (HHR) by the very low molecular weight heparin (VLMWH) CY 222, versus the rinsing procedure without heparin (RPWH) a randomized cooperative trial [abstract]. Kidney International 1989;35(1):257. [CENTRAL: CN-01658401]
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Mujais 1996a {published data only}
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Naumnik 2003 {published data only}
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    1. Naumnik B, Borawski J, Pawlak K, Mysliwiec M. Effects of low-molecular weight heparin (enoxaparin sodium) and unfractionated heparin on circulating endothelial markers in hemodialysis patients: a randomized prospective study [abstract no: O47]. Nephrology Dialysis Transplantation 2002;17(Suppl 12):15. [CENTRAL: CN-00509383]
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Naumnik 2007 {published data only}
    1. Naumnik B, Borawski J, Pawlak K, Mysliwiec M. Enoxaparin but no unfractionated heparin causes a dose-dependent increase in circulating TGF-b1 during hemodialysis: a cross-over study [abstract no: F-FC053]. Journal of the American Society of Nephrology 2006;17(Abstracts):48A. [CENTRAL: CN-00615865]
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Nurmohamed 1991 {published data only}
    1. Nurmohamed MT, Stevens P, Lins R, ten Cate J, Hoek JA, Buller HR, et al. Efficacy and safety of a low molecular weight heparin versus unfractionated heparin in 100 chronic hemodialysis patients during 6 months [abstract no: P58]. British Journal of Haematology 1990;76(Suppl 1):24. [CENTRAL: CN-00724946]
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Nurmohamed 1993 {published data only}
    1. Nurmohamed MT, Hoek JA, ten Cate J, Krediet RT, Buller HR. A randomized cross-over study comparing the efficacy and safety of two dosages dermatan sulphate (DS) and standard heparin in six chronic haemodialysis patients [abstract no: P56]. British Journal of Haematology 1990;76(Suppl 1):23.
    1. Nurmohamed MT, Knipscheer HC, Stevens P, Krediet RT, Roggekamp MC, Berckmans RJ, et al. Clinical experience with a new antithrombotic (dermatan sulfate) in chronic hemodialysis patients. Clinical Nephrology 1993;39(3):166-71. [MEDLINE: ] - PubMed
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Orsag 2021 {published data only}ACTRN12613001340729
    1. Orsag A, Bozic-Mijovski M, Hudoklin S, Simcic S, Gubensek J. Biocompatibility parameters with standard and increased dose of citrate in hemodialysis-a randomized trial. Journal of Clinical Medicine 2021;10(13):2987. [PMID: ] - PMC - PubMed
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Ota 1997 {published data only}
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Ota 1997a {published data only}
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Park 2012b {published data only}
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Polkinghorne 2002b {published data only}
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Rota 1995 {published data only}
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Ryan 1991 {published data only}
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    1. Ryan KE, Lane DA, Flynn A, Shepperd J, Ireland HA, Curtis JR. Dose finding study of a low molecular weight heparin, Innohep, in haemodialysis. Thrombosis & Haemostasis 1991;66(3):277-82. [MEDLINE: ] - PubMed
Rydzewska‐Rosolowska 2009 {published data only}
    1. Naumnik B, Rydzewska-Rosolowska A, Mysliwiec M. Different effects of enoxaparin, nadroparin, and dalteparin on plasma TFPI during hemodialysis: a prospective crossover randomized study. Clinical & Applied Thrombosis/Hemostasis 2011;17(5):480-6. [MEDLINE: ] - PubMed
    1. Rydzewska-Rosolowska A, Borawski J, Mysliwiec M. Different low-molecular-weight heparins vs unexpected depletion of MCP-1 during hemodialysis: a randomized cross-over study [abstract no: SA-PO2450]. Journal of the American Society of Nephrology 2009;20(Abstract Suppl):673A.
    1. Rydzewska-Rosolowska A, Borawski J, Mysliwiec M. Hepatocyte growth factor/activin A/follistatin system activation during hemodialysis with different low molecular weight heparins. Renal Failure 2009;31(9):791-7. [MEDLINE: ] - PubMed
    1. Rydzewska-Rosolowska A, Borawski J, Mysliwiec M. High plasma endostatin level unaffected by low-molecular weight heparin in hemodialysis patients--a preliminary report. Advances in Medical Sciences 2009;54(2):199-202. [MEDLINE: ] - PubMed
    1. Rydzewska-Rosolowska A, Borawski J, Naumnik B, Mysliwiec M. Different low-molecular-weight heparins vs remarkable hepatocyte growth factor/activin A/follistatin system activation during hemodialysis: a randomized cross-over study [abstract no: SaP387]. Nephrology Dialysis Transplantation 2007;22(Suppl 6):vi364.
SAFE 2021 {published data only}
    1. Meijers B, Vandenbosch I, Bammens B, De Vusser K, Van Craenenbroeck A, Claes K, et al. Heparin-free dialysis: A phase II pilot study using asymmetric triacetate (ATA) cellulose dialyzers. Nephrology Dialysis Transplantation 2020;35(Suppl 3):iii1391. [EMBASE: 633422393]
    1. Vandenbosch I, Dejongh S, Claes K, Bammens B, De Vusser K, Van Craenenbroeck A, et al. Strategies for asymmetrical triacetate dialyser heparin-free effective haemodialysis: the SAFE study. Clinical Kidney Journal 2021;14(8):1901-7. [MEDLINE: ] - PMC - PubMed
Sagedal 2011 {published data only}
    1. Sagedal S, Witczak BJ, Osnes K, Hartmann A, Os I, Eikvar L, et al. A heparin-coated dialysis filter (AN69 ST) does not reduce clotting during hemodialysis when compared to a conventional polysulfone filter (Fx8). Blood Purification 2011;32(3):151-5. [MEDLINE: ] - PubMed
Saltissi 1999 {published data only}
    1. Saltissi D, Morgan C, Westhuyzen J, Healy H. Comparison of low molecular weight heparin (enoxaparin sodium, clexane) and standard unfractionated heparin for haemodialysis anticoagulation [abstract no: 33]. Nephrology 2000;5(1-2 Suppl):A11. [CENTRAL: CN-01657893] - PubMed
    1. Saltissi D, Morgan C, Westhuyzen J, Healy H. Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractionated heparin for haemodialysis anticoagulation. Nephrology Dialysis Transplantation 1999;14(11):2698-703. [MEDLINE: ] - PubMed
Sanchez‐Canel 2012 {published data only}
    1. Sanchez-Canel JJ, Pons-Prades R, Salvetti ML, Seores A, Vazquez M, Perez-Alba A, et al. Evaluation of coagulation and anti-Xa factor when using a heparin-coated AN69ST® dialyser. Nefrologia 2012;32(5):605-12. [MEDLINE: ] - PubMed
Saxena 1996 {published data only}
    1. Saxena S, Bhowmik D, Ahlawat S, Jain PK, Tiwari SC, Dash SC. Low molecular weight heparins in hemodialysis. Indian Journal of Nephrology 1996;6(2):42-4. [CENTRAL: CN-01657891]
Schott 2010 {published data only}
    1. Schott U, Nilsson LG, Broman M, Engstrom M. Monitoring of low molecular weight heparin anticoagulation during haemodialysis with a Sonoclot Analyzer. Perfusion 2010;25(4):191-6. [MEDLINE: ] - PubMed
Sela 2001 {published data only}
    1. Sela S, Shurtz-Swirski R, Shapiro G, Nasser L, Hamzi M, Shasha SM, et al. Oxidative stress during hemodialysis: effect of heparin. Kidney International - Supplement 2001;78:S159-63. [MEDLINE: ] - PubMed
Shi 2008 {published data only}
    1. Shi M, Chen H, Liu H, Qiu C, Jia R, Ding G. Anticoagulant effect of argatroban in ESRD patients during induction period of hemodialysis with central venous catheter access [abstract no: F-PO1582]. Journal of the American Society of Nephrology 2008;19(Abstracts Issue):462A. [CENTRAL: CN-01912344]
Siamopoulos 1996 {published data only}
    1. Siamopoulos KC, Elisaf M, Pappas M, Koulouridis E, Germanos N. The long-term influence of low molecular weight heparin on lipid parameters in hemodialysis patients [abstract]. Nephrology Dialysis Transplantation 1996;11(6):A186. [CENTRAL: CN-00261281]
Stefoni 2002 {published data only}
    1. Stefoni S, Cianciolo G, Donati G, Coli L, La Manna G, Raimondi C, et al. Standard heparin versus low-molecular-weight heparin. A medium-term comparison in hemodialysis. Nephron 2002;92(3):589-600. [MEDLINE: ] - PubMed
Stegmayr 2013 {published data only}
    1. Stegmayr BG, Jonsson P, Mahmood D. A significant proportion of patients treated with citrate containing dialysate need additional anticoagulation. International Journal of Artificial Organs 2013;36(1):1-6. [MEDLINE: ] - PubMed
Swartz 1979 {published data only}
    1. Swartz RD, Port FK. Preventing hemorrhage in high-risk hemodialysis: regional versus low-dose heparin. Kidney International 1979;16(4):513-8. [MEDLINE: ] - PubMed
Tabiban 2017 {published data only}
    1. Tabiban S, Rahbar K, Ghadrdoost B, Zahed NS, Falaknazi K, Piraste H. Comparison of enoxaparin sodium and standard heparin for hemodialysis anticoagulation. Nephro-Urology Monthly 2017;9(2):e43443. [EMBASE: 614723127]
Tai 2015 {published data only}
    1. Leung K, Ravani P, Quinn RR, Scott-Douglas N, MacRae JM. Citrasate versus acetate dialysate on intradialytic heparin dose: a randomized crossover study [abstract no: TH-PO904]. Journal of the American Society of Nephrology 2014;25(Abstract Suppl):319A.
    1. Leung KC, Tai DJ, Ravani P, Quinn RR, Scott-Douglas N, Macrae JM. Citrate vs. acetate dialysate on intradialytic heparin dose: a double blind randomized crossover study. Hemodialysis International 2016;20(4):537-47. [MEDLINE: ] - PubMed
    1. Tai DJ, Leung K, Ravani P, Quinn RR, Scott-Douglas N, Macrae JM. The effect of citrate dialysate on intradialytic heparin dose in haemodialysis patients: study design of a randomised controlled trial. BMC Nephrology 2015;16(1):147. [MEDLINE: ] - PMC - PubMed
Tang 2022 {published data only}
    1. Tang X, Chen D, Zhang L, Fu P, Chen Y, Xiao Z, et al. Application of regional citrate anticoagulation in patients at high risk of bleeding during intermittent hemodialysis: a prospective multicenter randomized controlled trial. Journal of Zhejiang University SCIENCE B 2022;23(11):931-42. [PMID: ] - PMC - PubMed
ten Cate 1985 {published data only}
    1. ten Cate JW, Krediet R, Stoffels H, Ridder R, Sturk A. A randomized crossover study of heparin versus LMW Heparin Kabi 2165 in chronic hemodialysis patients [abstract]. Thrombosis & Haemostasis 1985;54(1):319. [CENTRAL: CN-00520300]
Teo 2004 {published data only}
    1. Teo BW, Perez C, Boyle J, Larive B, Heyka R. A comparison of four heparin protocols to maintain dialyzer fiber bundle volume during dialysis [abstract no: F-PO365]. Journal of the American Society of Nephrology 2004;15(Oct):147A. [CENTRAL: CN-01658406]
Vanommeslaeghe 2021 {published data only}
    1. Vanommeslaeghe F, Josipovic I, Boone M, Dhondt A, Van Biesen W, Eloot S. A randomized cross-over study with objective quantification of the performance of an asymmetric triacetate and a polysulfone dialysis membrane using different anticoagulation strategies [Erratum in: Clin Kidney J. 2020 Sep 04;14(1):463-464]. Clinical Kidney Journal 2021;14(1):398–407. [MEDLINE: ] - PMC - PubMed
Vanuytsel 1999 {published data only}
    1. Vanuytsel JL, Lins RL, Zachee P, Mattheeussen J, Hosten S, Lens S, et al. Comparison of different routes of administration of nadroparin in hemodialysis. Clinical Nephrology 1999;52(5):322-5. [MEDLINE: ] - PubMed
Verzan 2004 {published data only}
    1. Verzan C, Capsa D, Covic A, Mota E, Verzan M, Barbulescu C, et al. Comparison between tinzaparin and standard heparin for chronic hemodialysis [abstract no: SP466]. In: 41st Congress. European Renal Association. European Dialysis and Transplantation Association; 2004 May 15-18; Lisbon, Portugal. 2004:175. [CENTRAL: CN-00509542]
Von Bonsdorff 1990 {published data only}
    1. Von Bonsdorff M, Stiekema J, Harjanne A, Alapiessa U. A new low molecular weight heparinoid Org 10172 as anticoagulant in hemodialysis. International Journal of Artificial Organs 1990;13(2):103-8. [MEDLINE: ] - PubMed
Wang 2014b {published data only}
    1. Wang T, Zhang L, Chen Z, Fu P. Evaluation of the application of regional citrate anticoagulation in sustained low efficiency hemodialysis. Chung-Hua Nei Ko Tsa Chih [Chinese Journal of Internal Medicine] 2014;53(12):953-6. [MEDLINE: ] - PubMed
Wang 2022 {published data only}
    1. Wang W, Zhang S, Li Y, Wu X, Yang H, Lv J, et al. Application of simplified regional citrate anticoagulation in hemodialysis patients with high risk of bleeding. Clinical Nephrology 2022;97(6):311-20. [PMID: ] - PubMed
Wiegmann 1987 {published data only}
    1. Wiegmann TB, MacDougall ML, Diederich DA. Long-term comparisons of citrate and heparin as anticoagulants for hemodialysis. American Journal of Kidney Diseases 1987;9(5):430-5. [MEDLINE: ] - PubMed
Wong 2016 {published data only}
    1. Wong SS, Lau WY, Chan PK, Wan CK, Cheng YL. Low-molecular weight heparin infusion as anticoagulation for haemodialysis. Cinical Kidney Journal 2016;9(4):630-5. [MEDLINE: ] - PMC - PubMed
Wong 2018 {published data only}
    1. Wong S, Lau WY, Ng ML, Chan SY, Chan SF, Cheng YL. Comparative study on nadroparin versus unfractionated heparin as anticoagulation for nocturnal home haemodialysis [abstract no: 83]. Nephrology 2020;25(Suppl 1):22. [EMBASE: 633928489]
    1. Wong SS, Lau WY, Ng ML, Chan SY, Chan SF, Chan PK, et al. Clinical study on low-molecular weight heparin infusion as anticoagulation for nocturnal home haemodialysis. Nephrology 2018;23(4):317-22. [MEDLINE: ] - PubMed
Xiao 2010 {published data only}
    1. Xiao Q, Sun XF, Zhang D, Ma ZF, Wu MG, Wang H, et al. Appropriate dosage of unfraction heparin and low molecular weight heparin in hemodialysis patients. Chung-Hua i Hsueh Tsa Chih [Chinese Medical Journal] 2010;90(3):187-91. [MEDLINE: ] - PubMed
Xie 2011c {published data only}
    1. Xie H, Lin H, Chen S, Yang N, Chen J. Comparison of anticoagulation using regional heparin, heparin-free and low molecular weight heparins in hemodialysis patients with high risk of bleeding. Journal of Dalian Medical University 2011;33(1):46-50. [EMBASE: 361554386]

References to studies excluded from this review

Akizawa 1988 {published data only}
    1. Akizawa T, Kitaoka T, Sato M, Koshikawa S, Hirasawa Y, Kazama M, et al. Comparative clinical trial of regional anticoagulation for hemodialysis. ASAIO Transactions 1988;34(3):176-8. [MEDLINE: ] - PubMed
Bernis 1995 {published data only}
    1. Bernis C, Sanz P, Motellon J, Cruz Cardenal M, Gruss E, Munoz E, et al. Utility of low molecular weight heparin in hemodialysis hipertriglyceridemia [abstract]. In: ISN XIII International Congress of Nephrology; 1995 Jul 2-6; Madrid, Spain. 1995:529.
Bhomi 2008 {published data only}
    1. Bhomi KK, Shrestha S, Bhattachan CL. Role of systemic anticoagulation in patients undergoing vascular access surgery. Nepal Medical College Journal: NMCJ 2008;10(4):222-4. [MEDLINE: ] - PubMed
Cicerello 1994 {published data only}
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Crowther 2002 {published data only}
    1. Crowther MA, Clase CM, Margetts PJ, Julian J, Lambert K, Sneath D, et al. Low-intensity warfarin is ineffective for the prevention of PTFE graft failure in patients on hemodialysis: a randomized controlled trial. Journal of the American Society of Nephrology 2002;13(9):2331-7. [MEDLINE: ] - PubMed
D'Ayala 2008 {published data only}
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Freudiger 1990 {published data only}
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Harenberg 1993 {published data only}
    1. Harenberg J, Haaf B, Schafer M, Dempfle CE, Stehle G, Heene DL. Anti-factor Xa determination in blood: a new method for controlling heparin therapy. Seminars in Thrombosis & Hemostasis 1993;19 Suppl 1:79-85. [MEDLINE: ] - PubMed
Heindel 2023 {published data only}
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Hofbauer 1999 {published data only}
    1. Hofbauer R, Moser D, Frass M, Oberbauer R, Kaye AD, Wagner O, et al. Effect of anticoagulation on blood membrane interactions during hemodialysis. Kidney International 1999;56(4):1578-83. [MEDLINE: ] - PubMed
Hombrouckx 1994 {published data only}
    1. Hombrouckx R, Devos JY, Larno L. Standard heparin (SH) versus 3 low-molecular-weight heparins (LMWH) in chronic dialysis [abstract]. Nephrology Dialysis Transplantation 1994;9(7):988. [CENTRAL: CN-00261022]
Hory 1982 {published data only}
    1. Hory B, Saunier F, Roy C, Renevier A, Kieffer Y, Saint-Hillier Y, et al. Prostacyclin versus regional heparinisation during haemodialysis (author's transl). Nouvelle Presse Medicale 1982;11(32):2393-97. [MEDLINE: ] - PubMed
Hory 1987 {published data only}
    1. Hory B, Cachoux A, Saunier F, Kieffer Y, Laroze M, Henriet MT, et al. Comparative study of heparin and a very low molecular-weight heparin in hemodialysis in chronic renal insufficiency. Presse Medicale 1987;16(19):955-8. [MEDLINE: ] - PubMed
Hu 2011 {published data only}
    1. Hu HH, Hsu CY, Fang HC, Lee PT, Chen CL, Chang TY, et al. Low-dose heparin retention in temporary hemodialysis double-lumen catheter does not increase catheter occlusion and might reduce risk of bleeding. Blood Purification 2011;32(3):232-7. [MEDLINE: ] - PubMed
Hur 2004 {published data only}
    1. Hur YS, Jang IS, Lee MS, Lee EN, Lee HJ, Song GS, et al. Adequacy of individualized heparinization during hemodialysis. Korean Journal of Nephrology 2004;23(2):300-8. [CENTRAL: CN-01657892]
Journois 1990 {published data only}
    1. Journois D, Safran D, Castelain MH, Chanu D, Drevillon C, Barrier G. Comparison of the antithrombotic effects of heparin, enoxaparin and prostacycline in continuous hemofiltration. Annales Francaises d Anesthesie et de Reanimation 1990;9(4):331-7. [MEDLINE: ] - PubMed
Kagawa 1997 {published data only}
    1. Kagawa S, Kan M, Kawashima S, Miyake S, Terao N, Obayashi S, et al. Effects of low-molecular-weight heparin on hypertriglyceridemia in chronic hemodialysis patients - Comparison with unfractionated standard heparin. Nishinihon Journal of Urology 1997;59(3):240-52. [EMBASE: 27166605]
Kamper 1997 {published data only}
    1. Kamper AM, Lins RL, Zachee P, Van Bergen S, Hosten S, Daelemans R. Safety of combining ticlopidine with nadroparin in the routine treatment of chronic hemodialysis patients. Nephron 1997;77(4):484-5. [MEDLINE: ] - PubMed
Kikic 2009 {published data only}
    1. Kikic Z, Lorenz M, Sunder-Plassmann G, Schillinger M, Regele H, Gyori G, et al. Effect of hemodialysis before transplant surgery on renal allograft function--a pair of randomized controlled trials. Transplantation 2009;88(12):1377-85. [MEDLINE: ] - PubMed
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Kim 1997 {published data only}
    1. Kim YG, Lee KB, et al. Efficiency of hemodialysis using heparin bound hemophan in patients at high risk of bleeding [abstract]. Nephrology Dialysis Transplantation 1997;12(9):A135. [CENTRAL: CN-00250815]
Kohler 1990a {published data only}
    1. Kohler M, Rucker S, Bambauer R, Heiden M, Weber U, Morsdorf S, et al. Comparison of low molecular weight heparin and unfractionated heparin in haemodialysis patients. Blut 1990;60(3):150. [CENTRAL: CN-00360305] - PubMed
Koutsikos 1994 {published data only}
    1. Koutsikos D, Kapetanaki A, Dalamanga A, Tzanatos H, Fourtounas C, Agroyannis B, et al. Cumulative effect of low-molecular-weight heparin in haemodialysis? A cross-over study [abstract]. Nephrology Dialysis Transplantation 1994;9(7):991. [CENTRAL: CN-00261026]
Kovaliv 1999 {published data only}
    1. Kovaliv YB, Kovaliv B, Vienken J. Kidney function and arterial hypertension (AH) changes of glomerulopathies (GP) patients, threated with fraiparine or conventional heparin (CH) monotherapy (MT) [abstract]. In: 36th Congress. European Renal Association. European Dialysis and Transplantation Association; 1999 Sep 5-8; Madrid, Spain. 1999:51. [CENTRAL: CN-00484685]
Krasinski 2004 {published data only}
    1. Krasinski Z, Dzieciuchowicz L, Kulesza J, Pietrzak I, Gabriel M, Krasinka B, et al. Influence of long-term therapy with low molecular weight heparin on patency of arterio-venous fistula for hemodialysis [abstract no: MP388]. In: 41st Congress. European Renal Association. European Dialysis and Transplantation Association; 2004 May 15-18; Lisbon, Portugal. 2004:360. [CENTRAL: CN-00509291]
Kronenberg 1995 {published data only}
    1. Kronenberg F, Konig P, Lhotta K, Steinmetz A, Dieplinger H. Low molecular weight heparin does not necessarily reduce lipids and lipoproteins in hemodialysis patients. Clinical Nephrology 1995;43(6):399-404. [MEDLINE: ] - PubMed
Lane 1986 {published data only}
    1. Lane DA, Ireland H, Flynn A, Anastassiades E, Curtis JR. Haemodialysis with low MW heparin: dosage requirements for the elimination of extracorporeal fibrin formation. Nephrology Dialysis Transplantation 1986;1(3):179-87. [MEDLINE: ] - PubMed
Lavaud 2005 {published data only}
    1. Lavaud S, Paris B, Maheut H, Randoux C, Renaux J, Rieu P, et al. Assessment of the heparin-binding AN69 ST hemodialysis membrane: II. Clinical studies without heparin administration. ASAIO Journal 2005;51(4):348-51. [MEDLINE: ] - PubMed
Limchiu 1998 {published data only}
    1. Limchiu LV, Gomez HAB. A prospective randomized controlled double blinded trial on the use of low molecular weight heparin in maintaining the patency of dual lumen catheter in hemodialysis [abstract]. In: Philippine Society of Nephrology; 1998 April 16-18; Mandalugoug City, Philippines. 1998. [CENTRAL: CN-00509322]
Ljungberg 1987 {published data only}
    1. Lins LE, Ljungberg B. Comparison between heparin and a low molecular weight heparin fragment given as single injections for anticoagulation during hemodialysis [abstract]. In: 24th Annual Congress. EDTA-ERA; 1987 Oct 25-29; West Berlin, Germany. 1987:125. [CENTRAL: CN-00626122]
    1. Ljungberg B, Blomback M, Johnsson H, Lins LE. A single dose of a low molecular weight heparin fragment for anticoagulation during hemodialysis. Clinical Nephrology 1987;27(1):31-5. [MEDLINE: ] - PubMed
Low 1996 {published data only}
    1. Low CL, Bailie G, Morgan S, Eisele G. Effect of a sliding scale protocol for heparin on the ability to maintain whole blood activated partial thromboplastin times within a desired range in hemodialysis patients. Clinical Nephrology 1996;45(2):120-4. [MEDLINE: ] - PubMed
Mahe 2003 {published data only}
    1. Aghasaryan M, Mazoyer E, Mahe I, dit Bal Sollier C, Simoneau G, Berge N, et al. A comparative pharmacodynamic study of anti-Xa activity to evaluate the accumulation effect of Tinzaparin and Enoxaparin given at prophylactic dose over 8 days in elderly patients with impaired renal function [abstract no: P1871]. Journal of Thrombosis & Haemostasis 2003;1(Suppl 1 July). [CENTRAL: CN-00508950]
    1. Mahe I, Aghassarian M, Bal dit Sollier C, Lacut K, Heilmann JJ, Mottier D, et al. A comparative pharmacodynamic study of anti-Xa activity to evaluate the accumulation effect of tinzaparin and enoxaparin given at prophylactic dose over 8 days in medical elderly patients with impaired renal function [abstract no: 44]. British Journal of Haematology 2006;133(Suppl 1):38-9.
    1. Mahe I, Aghassarian M, Drouet L, Dit-Sollier CB, Lacut K, Heilmann JJ, et al. Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function: a comparative pharmacokinetic study. Thrombosis & Haemostasis 2007;97(4):581-6. [MEDLINE: ] - PubMed
    1. Mahe I, Bal dit Sollier C, Aghassarian M, Lacut K, Heilmann J, Bergmann J, et al. Comparative pharmacodynamic study of anti-Xa activity to evaluate the accumulation effect of tinzaparin and enoxaparin given at prophylactic dose over 8 days in medical elderly patients with impaired renal function [abstract]. Blood 2005;106(11 Part 1):118b.
Meyer 1999a {published data only}
    1. Meyer KB, Jenuleson CS, Vital A, Schmid CH, Whitson AB, Finkielsztein S. Control of post dialysis bleeding in patients on chronic oral anticoagulation therapy [abstract no: A1078]. Journal of the American Society of Nephrology 1999;10(Program & Abstracts):212A. [CENTRAL: CN-01658402]
Mokrzycki 2001 {published data only}
    1. Mokrzycki MH, Jean-Jerome K, Rush H, Zdunek MP, Rosenberg SO. A randomized trial of minidose warfarin for the prevention of late malfunction in tunneled, cuffed hemodialysis catheters. Kidney International 2001;59(5):1935-42. [MEDLINE: ] - PubMed
    1. Mokrzycki MH, Rush H, Jean-Jerome K, Rosenberg SO. Mini-dose warfarin for the prevention of tunneled-cuffed catheter (tcc) thrombosis [abstract no: A1082]. Journal of the American Society of Nephrology 1999;10(Program & Abstracts):213A. [CENTRAL: CN-01912348]
    1. Mokrzycki MH, Rush H, Jean-Jerome K, Zdunek MP, Rosenberg SO. Risk factors for late malfunction in tunneled-cuffed hemodialysis catheters and the efficacy of fixed, mini-dose warfarin [abstract no: A1015]. Journal of the American Society of Nephrology 2000;11(Sept):190-1A. [CENTRAL: CN-00626099]
Moor 2013 {published data only}
    1. Moor MB, Kruse A, Uehlinger DE, Eisenberger U. Arterial stiffness depends on serum ionized calcium levels during dialysis with regional citrate anticoagulation. Artificial Organs 2013;37(5):467-74. [MEDLINE: ] - PubMed
Moriniere 1989 {published data only}
    1. Moriniere P, Dieval J, Bayrou B, Roussel B, Renaud H, Fournier A, et al. Low-molecular-weight heparin Fraxiparin in chronic hemodialysis. A dose-finding study. Blood Purification 1989;7(6):301-8. [MEDLINE: ] - PubMed
Mujais 1996 {published data only}
    1. Mujais S, Chimeh H. Altering membrane thrombogenicity by heparin coating [abstract no: A0841]. Journal of the American Society of Nephrology 1996;7(9):1415. [CENTRAL: CN-00602131]
Neumann 2007 {published data only}
    1. Neumann K, Krainz A, Domroese U, Westphal S. Influence of hirudin in comparison to heparin on lipids during hemodialysis in patients with end-stage renal disease (ESRD) [abstract no: SA-PO669]. Journal of the American Society of Nephrology 2007;18(Abstracts Issue):489A. [CENTRAL: CN-01658399]
Noguchi 1990 {published data only}
    1. Noguchi M, Izumi K, Deguchi K, Endoh T, Tsuda M, Shirakawa S. Comparative study of low molecular weight heparin and unfractionated heparin in patients on maintenance hemodialysis. Rinsho Byori - Japanese Journal of Clinical Pathology 1990;24(8):177-86. [CENTRAL: 2172594] - PubMed
    1. Noguchi M. Comparative study of low molecular weight heparin and unfractionated heparin in patients on maintenance hemodialysis. Clinical Report 1990;24(8):421-30. [CENTRAL: CN-01657472] - PubMed
Parasrampuria 2015 {published data only}
    1. Parasrampuria DA, Marbury T, Matsushima N, Chen S, Wickremasingha PK, He L, et al. Pharmacokinetics, safety, and tolerability of edoxaban in end-stage renal disease subjects undergoing haemodialysis [Erratum in: Thromb Haemost. 2017 Apr 3;117(4):821]. Thrombosis & Haemostasis 2015;113(4):719-27. [MEDLINE: ] - PubMed
Puccini 1995 {published data only}
    1. Puccini R, Baicchi U, Aielli V, Paleologo G, Moriconi L, Pasquariello A, et al. Heparin treatment and renal failure progression [abstract]. In: ISN XIII International Congress of Nephrology; 1995 Jul 2-6; Madrid, Spain. 1995:238. [CENTRAL: CN-00509428]
Ravari 2008 {published data only}
    1. Ravari H, Kazemzade GH, Sarookhani A, Khashayar P. Effect of heparin on the patency of arteriovenous fistula. Acta Medica Iranica 2008;46(5):379-82. [EMBASE: 352801733]
Reinecke 2018 {published data only}
    1. Reinecke H, Engelbertz C, Bauersachs R, Breithardt G, Echterhoff HH, Gers J, et al. A randomized controlled trial comparing apixaban with the vitamin K antagonist phenprocoumon in patients on chronic hemodialysis: the AXADIA-AFNET 8 Study. Circulation 2023;147(4):296‐309. [DOI: 10.1161/CIRCULATIONAHA.122.062779] - DOI - PMC - PubMed
    1. Reinecke H, Jurgensmeyer S, Engelbertz C, Gerss J, Kirchhof P, Breithardt G, et al. Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA-AFNET 8 study. BMJ Open 2018;8(9):e022690. [MEDLINE: ] - PMC - PubMed
Rodger 2012 {published data only}
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Rodriguez Jornet 1994 {published data only}
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Ryan 1992 {published data only}
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Schrader 1988 {published data only}
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Taber 1997 {published data only}
    1. Taber T, Fishbane S, Brown P, Nelson D, Torry R. Use of enoxaparin to prevent PTFE hemodialysis graft venous anastomotic stenosis [abstract no: A0816]. Journal of the American Society of Nephrology 1997;8(Program & Abstracts):174A. [CENTRAL: CN-00447934]
VALKYRIE 2016 {published data only}
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References to studies awaiting assessment

Chirananthavat 2023 {published data only}
    1. Chirananthavat T, Hantrakul W. WCN23-0388 Effect of low-dose heparin as an anticoagulant protocol on the number of dialyzer reuses for maintenance hemodialysis. Kidney International Reports 2023;8(3):S316. [DOI: 10.1016/j.ekir.2023.02.707] - DOI
Elahi 2022 {published data only}
    1. Elahi R, Siddiqui MH, Rana MA, Qayyum MA, Iqbal W, Khalid MS, et al. The efficacy of taurolidine citrate solution versus heparin lock solution instilled in the catheter lumens of end stage renal disease patients on hemodialysis. Pakistan Journal of Medical and Health Sciences 2022;16(9):152‐4. [DOI: 10.53350/pjmhs22169152] - DOI
NCT01356615 {published data only}
    1. Lessan-Pezeshki M. Low molecular weight heparin for hemodialysis anticoagulation [Low molecular weight heparin (enoxaparin sodium) and standard unfractionated heparin for hemodialysis anticoagulation]. www.clinicaltrials.gov/ct2/show/NCT01356615 (first posted 19 May 2011).
Pokorney 2022 {published data only}
    1. Pokorney SD, Chertow GM, Al-Khalidi HR, Gallup D, Dignacco P, Mussina K, et al. Apixaban for patients with atrial fibrillation on hemodialysis: a multicenter randomized controlled trial. Circulation 2022;146(23):1735‐45. [DOI: 10.1161/CIRCULATIONAHA.121.054990] - DOI - PubMed
Verbout 2022 {published data only}
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von Groote 2023 {published data only}
    1. Groote T, Albert F, Meersch M, Koch R, Gerss J, Arlt B, et al. Evaluation of Proenkephalin A 119-159 for liberation from renal replacement therapy: an external, multicenter pilot study in critically ill patients with acute kidney injury. Critical Care (London, England) 2023;27(1):276. [PMID: ] - PMC - PubMed
Yoowannakul 2022 {published data only}
    1. Yoowannakul S, Boonsayomphu T. Efficacy of regional citrate anticoagulation vs. saline flushing during intermittent hemodialysis on blood circuit clotting prevention: a randomized clinical trial (The Citra-Saline-IHD) [abstract no: SA-PO464]. Journal of the American Society of Nephrology : JASN 2022;33:735. [EMBASE: 639543967]
Yousefi 2023 {published data only}
    1. Yousefi H, Hosseinifard M, Falaki M, Noghabi FA, Samimagham H, Yousefi M, et al. Durability of the two-lumen catheter in hemodialysis patients; ethanol 70%-heparin versus cefazolin-heparin: a randomized, double-blind clinical trial study. Journal of Nephropharmacology 2023;12(1):e10526. [EMBASE: 2019092857]

References to ongoing studies

ChiCTR1900024978 {published data only}
    1. Objective to compare the anticoagulant efficacy and safety of simplified citric acid anticoagulation and conventional citrate anticoagulation in hemodialysis patients: a cross controlled clinical trial. trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR1900024978 (date registered: 5 August 2019).
ChiCTR1900027928 {published data only}
    1. Safety and efficacy of regional citrate compared to non-heparin as anticoagulation in conventional dialysis of patients with a high risk of bleeding. trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR1900027928 (date registered: 10 December 2019).
ChiCTR2000034314 {published data only}
    1. Comparative efficacy and safety of two regional citrate anticoagulation protocols in hemodialysis: a randomized, open-label, cross-over controlled study. https://www.chictr.org.cn/hvshowproject.html?id=57232 (date registered: 2 July 2020).
ChiCTR2100047224 {published data only}
    1. The clinical research plan of citrate dialysate in hemodialysis anticoagulation effect. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2100047224 (date registered: 11 June 2021).
ChiCTR2200056615 {published data only}
    1. Clinical using study of 4% citrate injection for non-hemodialysis central venous catheter (CVC) closure in ICU patients: a three-blind, randomized, parallel grouping, standard control, single-center trial protocol. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2200056615 (date registered: 9 February 2022).
ChiCTR2200057383 {published data only}
    1. Comparison of different priming solutions for continuous venovenous hemofiltration with regional citrate anticoagulation. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2200057383 (date registered: 10 March 2022).
ChiCTR2200061027 {published data only}
    1. Clinical study of anticoagulant efficacy and safety of two topical citrate anticoagulant regimens in hemodialysis patients: an open, single-center randomized controlled study [Clinical study of anticoagulant efficacy and safety of two topical citrate anticoagulant regimens in hemodialysis patients]. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2200061027 (date registered: 15 June 2022).
ChiCTR2200063874 {published data only}
    1. Study on simplified citrate anticoagulation hemodialysis scheme suitable for grassroots promotion [Study on simplified citrate anticoagulation hemodialysis]. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2200063874 (date registered: 19 September 2022).
ChiCTR2300071613 {published data only}
    1. The safety and effectiveness of anticoagulation strategies of Nafamostat Mesilate for hemodialysis in patients at high risk of blood clotting: a single-center randomized trial. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300071613 (date registered: 19 May 2023).
CTIS2022‐502500‐75‐00 {published data only}
    1. DAN-WAR-D - Danish Warfarin-Dialysis Study: safety and efficacy of warfarin in patients with atrial fibrillation on dialysis -A nationwide parallel-group open randomized clinical trial. https://trialsearch.who.int/Trial2.aspx?TrialID=CTIS2022-502500-75-00 (date registered: 1 December 2022).
NCT05679024 {published data only}
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NCT05705076 {published data only}
    1. Efficacy of direct oral anticoagulants as a prophylactic anticoagulation of catheter induced thrombosis. https://clinicaltrials.gov/show/NCT05705076 (date first posted: 30 January 2023).
NCT05874674 {published data only}
    1. The safety of nafamostat mesylate for patients with high risk bleeding undergoing hemodialysis: a pilot study. https://clinicaltrials.gov/show/NCT05874674 (date first posted: 25 May 2023).
TCTR20230107004 {published data only}
    1. The efficacy of trisodium citrate versus heparin for permanent cuffed tunneled catheter lock in chronic hemodialysis patients. https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20230107004 (date of registration: 18 October 2023).

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References to other published versions of this review

Jose 2015
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Associated data