INCREASED THROMBIN GENERATION IN PATIENTS WITH CHRONIC-RENAL-FAILURE

The plasma concentration of prothrombin fragment 1 + 2 (F1 + 2) is con sidered a very sensitive parameter for specific detection of latent hy percoagulability. To evaluate the degree of hypercoagulation associate d with chronic uremia, we measured F1 + 2 by ELISA in the plasma of 51 patients with severe or end-stage chronic renal failure (35 males, 16 females, aged 22-81 years): 24 on dietary treatment, 15 on combined d ietary and once a week hemodialysis, and 12 on regular maintenance hem odialysis; 33 healthy subjects served as a control group. Plasma F1 2 showed a significant elevation in the group on dietary treatment; it was further increased in the group on once a week hemodialysis, and e ven more markedly increased in the group On maintenance hemodialysis. In patients on dietary treatment a positive correlation was found betw een plasma F1 + 2 and serum creatinine. In patients on maintenance hem odialysis, no increase in the F1 + 2 plasma level was found during the course of a single hemodialysis session. Low molecular weight heparin , administered to 7 patients on dietary treatment, caused a marked dro p in the F1 + 2 plasma level, providing evidence that the elevation in F1 + 2 indicates an accelerated in vivo thrombin generation rather th an impaired renal catabolism. The enhanced coagulation activation appe ars to;be related to the reduction of residual renal function, i.e., t o the severity of renal failure, and may contribute to the increased r isk of vascular events in uremic patients.