Summary
The optimal intensity of oral anticoagulant therapy for the prevention of thromboembolism
in patients with antiphospholipid antibodies (APLA) and systemic lupus erythematosus
is controversial. Retrospective studies have suggested that patients with APLA are
resistant to oral anticoagulant therapy, with a targeted International Normalization
Ratio (INR) of 2.0 to 3.0, and that a higher intensity of anticoagulation (INR: 2.6
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
therapy, we performed a randomized trial in which 21 patients with APLA and systemic
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 four months. The main outcome
was the effect of each intensity of warfarin therapy 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 three warfarin intensities were compared to F1+2 levels in the placebo
group, there was a statistically significant decrease (p <0.05) in the patient group
receiving warfarin with a targeted INR of 2.0 to 2.5 at two, three and four months,
and in the patient group with a targeted of INR 1.5 to 1.9 at three months. We conclude
that in patients with APLA and systemic lupus erythematosus, warfarin therapy, with
a targeted INR of 2.0 to 2.5, is effective in suppressing coagulation activation,
and therefore, might be effective in preventing thromboembolism.
Keywords
Thromboembolism - antiphospholipid antibodies - anticoagulation