The optimized anticoagulation strategy in prolonged hemodialysis

Background During extended (nocturnal) hemodialysis (ENHD), the dose of low-molecular-weight heparin (LMWH) can be administered as a single injection or as a divided dose over different time points. Our hypothesis was that a single injection might be sufficient to maintain dialyzer fiber patency. In addition, we investigated whether the biochemical clotting parameter anti-Xa accurately predicts fiber blocking. Methods Our hypothesis was tested in 20 stable patients on ENHD in a random cross-over setting during two consecutive midweek sessions. The regular total dose of LMWH (i.e. enoxaparin, Clexane (R) 40-100 mg, Sanofi, Belgium) was either given (i) in a single injection at the dialysis start or (ii) divided over two injections, at the start and halfway the dialysis session. Blood samples were taken from the arterial blood line at different time points to determine plasma anti-Xa activity levels. Post-dialysis, the rinsed and dried hemodialyzers were scanned with a reference micro-computed tomography (mu CT) scanning technique, and non-blocked fibers were counted in a central cross-section of the dialyzer outlet potting (ImageJ, NIH, USA). Results The percentage of open fibers in the dialyzers after a single injection of LMWH [91 (61-96)%] versus divided administration [94 (79-98)%] was not different. Time averaged anti-Xa activity levels were clinically not significantly different between both sessions. Anti-Xa activity levels correlated with the administered anticoagulation doses normalized for body weight, but not with the percentages open fibers in the dialyzers. Conclusion Our results indicate that there is no need to administer enoxaparin over two injections for ENHD up to 8 h. The usefulness of monitoring anti-Xa levels to predict fiber patency, assessed by mu CT, can be questioned, but further clinical trials are needed. Lay Summary Anticoagulation remains necessary in hemodialysis to avoid clotting of the extracorporeal circuit. During extended (nocturnal) hemodialysis, the total dose of low-molecular-weight heparin (LMWH) anticoagulation can be administered as a single injection or divided over different time points. To investigate differences in clotting between these two scenarios, 20 stable patients were randomized over the two arms during two consecutive midweek sessions. Patients received their regular total dose of LMWH either in a single injection at the dialysis start or divided over two injections, i.e. at start and halfway the session. Blood was sampled from the inlet blood line at different time points to determine plasma anti-Xa activity levels, and hemodialyzers were scanned post dialysis with micro-computed tomography technique to quantify the percentage open fibers. Since no difference in percentage open fibers was observed, there is no need to divide the dose of LMWH. Further, the usefulness of anti-Xa to predict fiber patency can be questioned, but further clinical trials are needed.