Suppression of hemostatic system activation by oral anticoagulants in the blood of patients with thrombotic diatheses

Abstract

RIAs for hemostatic system activation were employed to study patients who were anticoagulated with warfarin. The mean prothrombin fragment F1+2 concentration in stably anticoagulated individuals without an inherited thrombotic diathesis (mean prothrombin time [PT] ratio [PT of patient/PT of normal plasma pool] = 1.74) was 0.231 nM as compared with a mean plasma F1+2 level of 1.68 nM for a nonanticoagulated control group (P < 0.0001). The initiation of oral anticoagulants in two subjects who did not exhibit protein C deficiency led to a paradoxical increase in F1+2 levels during the first day of therapy. We have also shown that a relatively low intensity regimen of warfarin (PT ratio < 1.2) may reduce elevated concentrations of F1+2 into the normal range in patients with a history of recurrent thromboembolism. The mean F1+2 level in antithrombin-deficient individuals on warfarin was significantly elevated (mean = 0.714 nM) as compared with that in anticoagulated subjects with protein C deficiency (mean = 0.205 nM) or in those without an inherited thrombotic disorder (P < 0.01) at equivalent levels of intensity of oral anticoagulation. We therefore conclude that the effect of warfarin on hemostatic system activation is modulated by the endogenous heparan sulfate-antithrombin mechanism.