The effects of low-intensity warfarin on coagulation activation in patients with antiphospholipid antibodies and systemic lupus erythematosus

The optimal intensity of oral anticoagulant therapy for the prevention of t hromboembolism in patients with antiphospholipid antibodies (APLA) and syst emic lupus erythematosus is controversial. Retrospective studies have sugge sted that patients with APLA are resistant to oral anticoagulant therapy, w ith a targeted International Normalization Ratio (INR) of 2.0 to 3.0, and t hat a higher intensity of anticoagulation (INR: 1.6 to 4.5) is required to prevent recurrent thromboembolism. To investigate if patients with APLA are resistant to the anticoagulant effect Of low intensities of warfarin thera py, we performed a randomized trial in which 21 patients with APLA and syst emic lupus erythematosus were allocated to receive one of three intensities of warfarin (INR: 1.1 to 1.4, 1.5 to 1.9 or 2.0 to 2.5) or placebo for fou r months. The main outcome was the effect of each intensity of warfarin the rapy on prothrombin fragment 1+2 level (F1+2). that was used as a marker of coagulation activation. When F1+2 levels in patients allocated to the thre e warfarin intensities were compared to F1+2 levels in the placebo group, t here was a statistically significant decrease (p < 0.05) in the patient gro up receiving warfarin with a targeted INR of 2.0 to 2.5 at two, three and f our months, and in the patient group with a targeted of INR 1.5 to 1.9 at t hree months. We conclude that in patients with APLA and systemic lupus eryt hematosus, warfarin therapy, with a targeted INR of 2.0 to 2.5, is effectiv e in suppressing coagulation activation, and therefore, might be effective in preventing thromboembolism.