Introduction: Systemic anticoagulation is administered during hemodialysis to prevent clotting of the extracorporeal circuit. The role of contact-system activation in thrombin generation during hemodialysis using current-era dialyzer membranes is unknown. Methods: We performed a single-center randomized crossover study. Ten patients treated with hemodialysis underwent 3 standardized hemodialysis sessions. For every patient, each session was performed with a different type of dialyzer membrane (polyphenylene [PP], polymethylmetacrylate [PMMA], polyethylenimine-coated polyacrylonitrile [AN69ST]). Blood samples were collected before and 5, 15, 30,90, and 240 minutes after blood pump start to evaluate coagulation activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1þ2 [PF1þ2], activated factor XII [FXIIa], kallikrein, activated factor XI [FXIa]). Plasma of healthy volunteers (n ¼ 20) was used as a reference. Results: Baseline TAT and PF1þ2 levels were higher in hemodialysis patients compared to healthy controls (median [interquartile range] for TAT: 3.3 [2.9–4.2] vs. 2.4 [2.3–2.5] mg/l [P ¼ 0.0002] and for PF1þ2: 647 [478–737] vs. 138 [125–254] pmol/l [P < 0.0002]). Despite the use of systemic anticoagulation, TAT further increased during treatment, with the increase starting after 30 minutes (median TAT at t240: 9.0 mg/l (PP), 5.5 mg/l (PMMA), and 7.2 mg/l (AN69ST), all P < 0.05 vs. baseline). Contact-system markers FXIIa and kallikrein did not differ significantly between dialysis patients and healthy controls, whereas baseline FXIa levels were significantly lower in dialysis patients compared to healthy controls (P ¼ 0.001). Levels of all contact-system markers remained unchanged during hemodialysis with all types of dialyzer membranes. Conclusions: Routine hemodialysis using systemic heparin anticoagulation induces coagulation activation without measurable contact-system activation.
Original languageEnglish
Pages (from-to)831-838
Number of pages8
JournalKidney international reports
Issue number6
Publication statusPublished - Jun 2020


  • blood coagulation
  • clotting
  • factor Xia
  • factor XIIa
  • hemodialysis
  • plasma kallikrein


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