PMID- 38189593 OWN - NLM STAT- MEDLINE DCOM- 20240109 LR - 20240327 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 1 IP - 1 DP - 2024 Jan 8 TI - Anticoagulation for people receiving long-term haemodialysis. PG - CD011858 LID - 10.1002/14651858.CD011858.pub2 [doi] LID - CD011858 AB - 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; I(2) = 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; I(2) = 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. CI - Copyright (c) 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Natale, Patrizia AU - Natale P AD - Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy. AD - Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, Universityof Foggia, Foggia, Italy. AD - Sydney School of Public Health, The University of Sydney, Sydney, Australia. FAU - Palmer, Suetonia C AU - Palmer SC AD - Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand. FAU - Ruospo, Marinella AU - Ruospo M AD - Sydney School of Public Health, The University of Sydney, Sydney, Australia. FAU - Longmuir, Henrietta AU - Longmuir H AD - School of Medicine, University of Tasmania, Hobart, Australia. FAU - Dodds, Benjamin AU - Dodds B AD - School of Medicine, University of Tasmania, Hobart, Australia. FAU - Prasad, Ritam AU - Prasad R AD - Department of Haematology/Pathology, Royal Hobart Hospital, Hobart, Australia. FAU - Batt, Tracey J AU - Batt TJ AD - Department of Haematology, Westmead Hospital, Westmead, Australia. FAU - Jose, Matthew D AU - Jose MD AD - School of Medicine, University of Tasmania, Hobart, Australia. FAU - Strippoli, Giovanni Fm AU - Strippoli GF AD - Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy. AD - Sydney School of Public Health, The University of Sydney, Sydney, Australia. AD - Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia. LA - eng SI - ClinicalTrials.gov/NCT03319680 SI - ClinicalTrials.gov/NCT00669721 SI - ClinicalTrials.gov/NCT02281045 SI - ClinicalTrials.gov/NCT02553889 SI - ClinicalTrials.gov/NCT00756145 SI - ClinicalTrials.gov/NCT00395824 SI - ClinicalTrials.gov/NCT03887468 SI - ClinicalTrials.gov/NCT03090984 SI - ClinicalTrials.gov/NCT00473109 SI - ClinicalTrials.gov/NCT01930396 SI - ClinicalTrials.gov/NCT01318486 SI - ClinicalTrials.gov/NCT03419923 SI - ClinicalTrials.gov/NCT03612856 SI - ClinicalTrials.gov/NCT04381234 SI - ClinicalTrials.gov/NCT01466959 SI - ClinicalTrials.gov/NCT03820401 SI - ClinicalTrials.gov/NCT02957877 SI - ClinicalTrials.gov/NCT00407641 SI - ClinicalTrials.gov/nct00260988 SI - ClinicalTrials.gov/NCT03799822 SI - ClinicalTrials.gov/NCT02610933 SI - ClinicalTrials.gov/NCT01356615 SI - ClinicalTrials.gov/NCT05679024 SI - ClinicalTrials.gov/NCT05705076 SI - ClinicalTrials.gov/NCT05874674 PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20240108 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 9005-49-6 (Heparin) RN - 0 (Anticoagulants) RN - 0 (Heparin, Low-Molecular-Weight) RN - 2968PHW8QP (Citric Acid) RN - 0 (Citrates) SB - IM UOF - doi: 10.1002/14651858.CD011858 MH - Adult MH - Child MH - Humans MH - Heparin/adverse effects MH - Anticoagulants/adverse effects MH - Renal Dialysis MH - Heparin, Low-Molecular-Weight/adverse effects MH - Citric Acid MH - Citrates MH - *Renal Insufficiency MH - Hemorrhage/chemically induced MH - *Thrombosis/etiology/prevention & control PMC - PMC10772979 COIS- Patrizia Natale: no relevant interests were disclosed. Suetonia C Palmer: no relevant interests were disclosed. Marinella Ruospo: no relevant interests were disclosed. Henrietta Longmuir: no relevant interests were disclosed. Benjamin Dodds: no relevant interests were disclosed. Luke Bereznicki: no relevant interests were disclosed. Ritam Prasad: no relevant interests were disclosed. Tracey Batt: Novo Nordisk (Independent Contractor - Other). Matthew D Jose: no relevant interests were disclosed. Giovanni FM Strippoli: no relevant interests were disclosed. EDAT- 2024/01/08 12:43 MHDA- 2024/01/09 06:42 PMCR- 2025/01/08 CRDT- 2024/01/08 09:59 PHST- 2025/01/08 00:00 [pmc-release] PHST- 2024/01/09 06:42 [medline] PHST- 2024/01/08 12:43 [pubmed] PHST- 2024/01/08 09:59 [entrez] AID - CD011858.pub2 [pii] AID - 10.1002/14651858.CD011858.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.