Increased thrombin generation in patients with chronic renal failure

Abstract

The plasma concentration of prothrombin fragment 1+2 (F1+2) is considered a very sensitive parameter for specific detection of latent hypercoagulability. To evaluate the degree of hypercoagulation associated 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 dietary and once a week hemodialysis, and 12 on regular maintenance hemodialysis; 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 even more markedly increased in the group on maintenance hemodialysis. In patients on dietary treatment a positive correlation was found between plasma F1+2 and serum creatinine. In patients on maintenance hemodialysis, 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 drop in the F1+2 plasma level, providing evidence that the elevation in F1+2 indicates an accelerated in vivo thrombin generation rather than impaired renal catabolism. The enhanced coagulation activation appears to be related to the reduction of residual renal function, i.e., to the severity of renal failure, and may contribute to the increased risk of vascular events in uremic patients.