Kinetics of Anti-Xa Activity during Combined Defibrotide - Heparin Administration in Hemodialysis

Abstract

Defibrotide, a polydesoxyribonucleotide derivative with antithrombotic and fibrinolytic activity, capable of inducing the release of PGI₂ from vascular endothelia, was proposed as an alternative to standard heparin coverage during blood dialysis for patients at risk of bleeding. The original procedure featured the preliminary washing of the dialysis circuit with heparin, which was then recirculated and eliminated, and the two drugs, heparin and defibrotide, are known to interact with each other. The purpose of this present study was to explore the ex-vivo heparin activity (assessed as anti-Xa activity) in diverse hemodialysis models using defibrotide (800 mg intravenous, in 4 bolus injections) and various dosages of heparin. Anti-Xa activity is negligible in dialysis conducted with defibrotide alone. When the circuit was prewashed with heparin (5000 and 2500 IU), there was evident anti-Xa activity (0.3-0.5 U/ml) in the first 30-60 minutes of dialysis; continuous heparin infusion (500 U/hour) resulted in high anti-Xa activity levels at the end of dialysis. Thus the best hemodialysis procedure for patients at high risk of bleeding should be one utilizing only defibrotide, or defibrotide plus small amounts of calcium heparin infused at the rate of 500 U/hour for not more than two hours.