Withdrawal of warfarin after deep vein thrombosis: effects of a low fixed dose on rebound thrombin generation

The optimal procedure for withdrawal of warfarin in patients with deep vein thrombosis (DVT) is still not defined. Rebound thrombin generation, which occurs after the withdrawal of warfarin, has been said to be associated with early recurrence of DVT. The aim of this study was to compare two procedures for warfarin withdrawal after the first episode of DVT with respect to rebound thrombin generation. Forty-one consecutive patients were randomly assigned to abrupt withdrawal of warfarin (group A), or to an additional month of warfarin, at the fixed dose of 1.25 mg/day (group B). Plasma samples were withdrawn for the assay of prothrombin fragment F1+2 (F1+2), protein C, factor VII and International Normalized Ratio (INR), before any anticoagulant treatment (I), during initial heparin (II) and full dose warfarin (III), at the end of full dose warfarin (IV) and then 1 (V), 4 (VI), 5 (VII) and 9 (VIII) weeks after randomization. The mean duration of full-dose warfarin treatment, the mean warfarin dose and the mean INR during full-dose warfarin treatment were similar in the two groups. A decrease in F1+2 was observed during heparin and warfarin treatment (II, 1.7 nmol/ml; III, 1.0 nmol/ml; IV, 0.7 nmol/ml; versus I, 3.5 nmol/ml; P < 0.01). After the withdrawal of warfarin, an increase in F1+2 was observed in both groups, but without significant statistical differences (group A: V, 1.2 nmol/ml; VI, 1.5 nmol/ml; VII, 1.6 nmol/ml; VIII, 1.1 nmol/ml; group B: V, 1.3 nmol/ml; IV, 1.5 nmol/ml; VII, 1.4 nmol/ ml; VIII, 1.4 nmol/ml). No significant difference between the two groups was observed in the recovery of protein C and factor VII. Four patients experienced a recurrence of DVT, three in group B and one in group A. Our findings confirm that rebound thrombin generation occurs in patients with DVT after the withdrawal of warfarin. Rebound thrombin generation is not reduced by a low, fixed dose of warfarin. Blood Coag Fibrinol 10:291-295 (C) 1999 Lippincott Williams & Wilkins.