Clinical Studies
Anticardiolipin Antibodies Predict Early Recurrence of Thromboembolism and Death Among Patients with Venous Thromboembolism Following Anticoagulant Therapy

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Abstract

Purpose: To compare the risk of recurrent venous thromboembolism in patients with and without antiphospholipid antibodies.

Patients and Methods: Anticardiolipin antibodies were tested 6 months after a first or second episode of venous thromboembolism. Of the patients with a first episode of venous thromboembolism only the 412 who received 6 months of anticoagulation were studied. Two hundred and eleven patients with a second episode received oral anticoagulation for 6 months or indefinitely. The therapy was targeted at an international normalized ratio (INR) of 2.0 to 2.85. All patients were followed up for 4 years after enrollment.

Results: Among the 412 patients with a first episode of venous thromboembolism the risk of recurrence was 29% in patients with anticardiolipin antibodies and 14% in those without antibodies (P = 0.0013). In those with antibodies, there was an increased risk during the first 6 months after cessation of anticoagulation. The risk of recurrence increased with the titer of the antibodies. Four-year mortality rate was 15% in those with antibodies and 6% in those without (P = 0.01). Among 34 patients with a second event of venous thromboembolism and anticardiolipin antibodies, there were no recurrences during anticoagulant therapy versus 20% in those who received only 6 months of treatment (P = 0.08).

Conclusions: The presence of elevated titers of anticardiolipin antibodies 6 months after an episode of venous thromboembolism is a predictor for an increased risk of recurrence and of death. Patients with anticardiolipin antibodies and venous thromboembolism seem to benefit from prolonged oral anticoagulation.

Section snippets

Patients

Patients were recruited during 3 years for a multicenter trial at 16 hospitals in Sweden of the optimum duration of oral anticoagulation after venous thromboembolism. A total of 1,124 patients of at least 15 years of age were included, 897 with a first episode of deep vein thrombosis or pulmonary embolism [14] and 227 patients with a second episode [15]. Main exclusion criteria were previously diagnosed malignant disease (152), severe current disease (137), insufficient ascertainment of venous

Results

Patients with a first or second episode of venous thromboembolism were recruited during the period April 12, 1988 to April 18, 1991. Most patients had deep-vein thrombosis (Table 1). We were unable to obtain samples for anticardiolipin antibodies for between 5% and 9% of the patients due to death or severe, intercurrent disease before the 6-month follow-up.

Among patients with a first episode of venous thromboembolism, 10 patients received shorter, and 14 received longer, anticoagulation than

Discussion

As opposed to most previous studies addressing the significance of antiphospholipid antibodies, our study is based on a sample of patients presenting with venous thromboembolism. In 15% of the patients tested after 6 months, elevated titers of anticardiolipin antibodies were found, corresponding to the APL-T type 1 syndrome [17]. Only two of these patients turned out to have systemic lupus erythematosus. Our analysis of antiphospholipid antibodies was limited to IgG anticardiolipin antibody,

Acknowledgements

Grants were obtained from Swedish Heart Lung Foundation, the Swedish Society of Medicine, the funds of the Karolinska Institute, Skandia, Trygg-Hansa, Triolab, Nycomed, and Stago.

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    The investigators and institutions participating in the Duration of Anticoagulation (DURAC) Study Group are listed in the Appendix A.

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