Absence of Measurable Contact System Activation of Coagulation during Hemodialysis: A Randomized Crossover Study

Background: Systemic anticoagulation is administered during hemodialysis to prevent clotting of the extracorporeal circuit. Novel specific contact system inhibitors induce anticoagulation without increasing bleeding risk. Aims: The present study aims to investigate whether the contact system of coagulation is activated during hemodialysis using current era hemodialysis membranes. Methods: Ten patients treated with hemodialysis underwent 3 standardised 4‐hours hemodialysis sessions. For every patient, each session was performed with a different type of dialyzer membrane (polysulphone, polymethylmetacrylate [PMMA], AN69ST), in random order. Blood samples to evaluate coagulation activation (thrombin‐antithrombin [TAT], Prothrombin Fragment 1+2 [PF1+2]) and, more specifically, activation of the contact system (fXIIa, kallikrein, fXIa) were collected before start and 5, 15, 30, 90 and 240 minutes after bloodpump start. Plasma of healthy volunteers (n=20) was used as control of the reference values provided by the assay manufacturers. Informed consent was obtained from all subjects. The study was approved by the Medical Ethics Committee of Universitair Ziekenhuis Brussel. Results: Baseline TAT and PF1+2 levels were increased in patients as compared to healthy controls (median [IQR] TAT: 3.8 [3.2‐6.3]µg/L vs 2.4 [2.3‐2.5]µg/L [p=0.0002]; median [IQR] PF1+2: 669 [474‐849]pmol/L vs 138 [125‐254]pmol/L [p< 0.0001]). TAT further increased during treatment, with the increase starting after 30 minutes (p=0.005, 0.03 and 0.007 for polysulphone, PMMA and AN69ST membranes respectively). Although the increase in PF1+2 during dialysis did not reach significance, post dialysis thrombin generation markers TAT and PF1+2 correlated strongly. Contact system markers fXIIa and kallikrein were similar in dialysis patients and healthy controls (p=0.06‐0.96) whereas baseline fXIa levels were significantly lower in patients compared to healthy controls (p< 0.0005). Levels of all contact system markers remained unchanged during hemodialysis. (figure) Conclusions: Hemodialysis patients present chronic coagulation activation demonstrated by baseline increased TAT and PF1+2 levels. TAT further increases during hemodialysis treatment without measurable activation of contact system markers.