LOW-DOSE WARFARIN DECREASES COAGULABILITY WITHOUT AFFECTING PROTHROMBIN COMPLEX ACTIVITY

Objectives. To asses the efficacy of a fixed, low dose of warfarin in lowering factor VII coagulant activity (FVII:C) and to investigate the effects on the plasma coagulation cascade. Design. An open pilot study with two dose levels of warfarin: 1.2 5 and 2.5 mg day-1 during two consecutive 4-week periods. All subjects received aspirin 75 mg day-1. Prothrombin fragment 1 + 2 (F(1+2)), protein C, protein S, FVII:C, factor X and P-prothrombin complex activity (P-PT) were measured at baseline, at 2-week intervals and 4 weeks after end of treatment. Coagulation activation peptide F(1+2) was used as a marker of thrombin formation [13]. Subjects. Twelve male patients with a history of myocardial infarction. Inclusion was made through a written questionnaire. Results. Warfarin 1.25 mg day-1 lowered FVII:C from 113 U dl-1 to 10(7) U dl-1 (P = 0.025) and F(1+2) from 1.60 nmol l-1 to 1.27 nmol l-1(P = 0.013) but had no effect on protein C or P-PT. A dose of 2.5 mg day-1 induced further lowering of FVII:C (91 U dl-1, P = 0.0042), and also of protein C from 116% to 99% (P = 0.034) and P-PT from 107% to 81% (P = 0.0096) mean values. Conclusion. Warfarin 1.2 5 mg day-1 seems to exert an anticoagulant effect without reduction in PT or the natural anticoagulant protein C and is suggested, in combination with aspirin, to be a safe and simple therapy against arterial thrombotic disease, making regular PT controls unnecessary.