FP459ANTICOAGULATION FOR HAEMODIALYSIS. A COCHRANE SYSTEMATIC REVIEW

Abstract

Introduction and Aims: Haemodialysis requires safe and effective anticoagula-tion to prevent clot formation during the procedure while minimising adverse effects including major bleeding. Low molecular weight heparins may provide more predictable anticoagulant effects and be simpler to administer than unfractionated heparin, but may accumulate in the presence of kidney failure to cause excess anticoagulation and bleeding. This Cochrane review assessed the benefits and harms of anticoagulation strategies for long-term haemodialysis. Methods: We searched the Cochrane Kidney and Transplant specialized register up to August 2017 for randomized controlled trials evaluating anticoagulation adminis-tered for haemodialysis treatment in adults with end-stage kidney disease. Treatment estimates were summarised by random effects meta-analysis. Risk of bias was assessed using the Cochrane tool. Evidence certainty was assessed using GRADE. Results: Forty-four trials (1648 participants) were eligible for inclusion. Treatments included low molecular weight heparin (LMWH), unfractionated heparin, citrate, danaparoid, dermatan, and direct thrombin inhibitors, and different routes, doses, and timing of administration. 29 studies used a crossover study design. The study duration was generally short with 17 studies evaluating effects during 1-2 haemodialysis sessions. Median study follow up was 1 month (range 1 week-12 months). The mean study age ranged between 39-74 years (median 60), and dialysis duration at time of participation ranged between 15-118 months (median). Most studies did not report adequate meth-ods to conceal treatment allocation or blinded participants and investigators to treatment allocation. In the 29 studies that employed a crossover design, findings were not reported for the end of the first phase of treatment to provide data for analysis. No study was designed to measure major bleeding outcomes, mortality or cardiovascular outcomes, or dialysis vascular access complications. 25 studies (999 participants) compared low molecular weight heparin with unfractionated heparin. The certainty of the evidence was very low or low for all outcomes. Two studies (115 participants) reported the outcome for extracorporeal dialysis circuit thrombosis, with only 1 study reporting one or more events. Accordingly, low molecular weight heparin has very uncertain effects on dialysis circuit thrombosis compared to unfractionated heparin. Four studies reported zero major bleeding events. No study reported time to achieve dialysis vascular access haemostasis. Low molecular weight heparin had uncertain effects on all-cause mortality in the 5 small studies reporting mortality events (216 participants; RR 2.41 [95% CI 0.62, 9.33]). A single study reported dialysis vascular access thrombosis. A single study reported the effect of low molecular weight heparin on dialysis adequacy, measured as KT/V. Data were not available for blood transfusion or plasma anti-factor Xa levels. Only one study reported minor bleeding events. Treatment effects of other anticoagulants such as dermatan, danaparoid, citrate, or direct thrombin inhibitors compared with unfractionated heparin or low molecular weight heparin were very uncertain as there were insufficient data to perform meta-analysis. Conclusions: Evidence for anticoagulation during haemodialysis is of very low certainty as trials have not been designed to measure important clinical outcomes.