Increased levels of soluble tissue factor during long-term treatment with warfarin in patients after an acute myocardial infarction.

Antithrombotic treatment with warfarin and/or aspirin is widely used in preventing recurrence of thrombotic events after an acute myocardial infarction (AMI). The objective of this study was to evaluate the long-term influence of warfarin at different INR levels and/or aspirin on some hemostatic variables in patients after an AMI. A subpopulation of the WARIS-II trial in which patients after an acute MI were randomly assigned to treatment with aspirin 160 mg d(-1), aspirin 75 mg d(-1) and warfarin (target INR 2.0-2.5) or warfarin (target INR 2.8-4.2) was studied. Fasting blood samples were collected before randomization 5-7 days after the AMI, after 6 weeks and 4 years for determinations of prothrombin fragment 1 + 2 (F1 + 2), soluble tissue factor (sTF), D-dimer and fibrinogen. In the warfarin-alone group as compared with the aspirin-alone group significantly lower levels of F1 + 2 and D-dimer (P < 0.001 for both), but significantly higher levels of sTF (P = 0.007) were found after 6 weeks. The same pattern was found after 4 years. When comparing the combined group with the aspirin alone group, similar profiles were seen. The levels of F1 + 2 in the combined group were, however, significantly higher than in the warfarin alone group after 6 weeks and 4 years (both P < 0.01). During long-term treatment with warfarin in patients after an AMI increased levels of sTF were found. However, significantly reduced levels of the coagulation products were obtained, indicating reduced thrombin generation. The increased levels of sTF during warfarin therapy are suggested to appear on the basis of reduced consumption.