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 [PI] ratio WPT 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 Fl+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.

Time course of thrombosis and fibrinolysis during total hip surgery

“…The short half-life of active thrombin precludes direct measurements. However, by conversion of prothrombin to thrombin, the amino terminal of prothrombin is cleaved to generate the inactive F1.2 fragment which is a sensitive marker of prothrombin activation and thrombin generation [33]. Our observations harmonize with the understanding that the risk of thrombosis starts perioperatively.…”

“…However, increased plasma concentrations of F1.2 and D-Dimer were found to correlate with thrombosis [33,37], and our results support the view that the interval between surgery and the first administration of prophylaxis is a critical variable that 189 may influence the occurrence of deep vein thrombosis in patients undergoing elective hip arthroplasty [38]. Thromboprophylaxis in close proximity to hip arthroplasty, either preoperatively or postoperatively, may balance efficacy and safety to prevent thrombosis on one hand and bleeding on the other hand.…”

Dietary lipids and thrombosis. Relationships to atherosclerosis.

“…Abnormalities in coagulation and fibrinolysis have generally been associated with venous thrombosis, whereas platelet and endothelial cell disturbances have been linked to the formation of arterial thrombi. 73 - 74 The reduction in mortality from CHD and the parallel reduction in pulmonary emboli and venous thrombosis observed in the United States during the last decade, when taken in concert with the observations from Norway during the Second World War, may suggest common pathogenetic factors for arterial and venous thrombosis. 15187578 However, the nearty fourfold increase of phlebograms taken in the United States during the last 15 years may indicate that the decline in pulmonary emboli has been due to increased vigor in the treatment and diagnosis of venous thrombosis, not to dietary changes.…”

Effect of low-intensity warfarin anticoagulation on level of activity of the hemostatic system in patients with atrial fibrillation. BAATAF Investigators.

“…Recently, a radioimmunoassay for monitoring the plasma level of the prothrombin fragment F,12 has been developed. [9][10][11][12] This activation peptide is liberated when prothrombin is converted to thrombin and thereby serves as an in vivo marker of thrombin generation and the degree of activity of the hemostatic system. In this article we report the level of prothrombin fragment F1+2 in patients with atrial fibrillation sampled from the Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF), a trial assessing the effect of lowintensity warfarin therapy on prevention of stroke.…”