Pathogenic effects of unfractionated heparin on hypercoagulability and vasculoendothelial dysfunction of regular hemodialysis patients

To clarify the effects of anticoagulant on coagulation, fibrinolysis, and vasculoendothelial dysfunction during hemodialysis (HD), randomized, prospected, comparative, clinical trials were performed on regular HD patients. Thirteen HD patients with hypercoagulability (determined by 250% excess factor VIII activity and/or factor VIII related antigen level) were randomly divided into two groups, one dialyzed with unfractionated heparin (UH), the other with low molecular weight heparin (LMWH) as an anticoagulant. For 8 months, coagulation, fibrinolysis and vasculoendothelial markers were measured monthly, immediately before HD. Dosages, determined by minimum requirement for preventing the coagulation of extracorporeal blood, were 95 ± 19U/kg for UH, and 38 ± 7 IU/kg for LMWH in each treatment (p<0.01). Although anti-Xa activity (aXa) with LMWH was greater than that with UH 1 hour after starting HD, activated partial thromboplastin time (aPTT) did not infer between the two groups. After HD there was no significant difference in aXa between the two groups, whereas the duration of aPTT was prolonged in the UH group, compared to that in the LMWH group. Modified antithrombin III (ATM) values, which represented the total antithrombin III activity bound with serine protease, were greater in both groups than in healthy subjects. ATM began to decrease in the LMWH group, but not in the UH group two months after starting the study, and this difference continued throughout the rest of the study period. In both HD groups, α2 plasmin inhibitor-plasmin complex (PIC) levels were higher than in healthy subjects, and decreased in the LMWH group, at 1, 4 and 5 months with no significant change in the UH group. The results suggest that UH, at least in part, contributes to abnormally increased coagulation and fibrinolysis activity, and the abnormality can be partially recovered by the use of LMWH as an HD anticoagulant.