Antiphospholipid Syndrome in Systemic Lupus Erythematosus (SLE) - Longterm Anticoagulation Therapy

8/15/01 (Chitaia)

Question: What trials or guidelines are available to support longterm or lifelong anticoagulation for patients with the antiphospholipid syndrome?

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 20347650 / PubMed Identifier: 10888978

Authors: Wahl DG. Bounameaux H. de Moerloose P. Sarasin FP.

Institution: Service de M&#x00E9;decine H, H&#x00F4;pital Central, CO#34, 29, avenue de Lattre de Tassigny, F54035 Nancy, France. dwahl@club-internet.fr.

Abstract: BACKGROUND: A high incidence of both arterial and venous thromboembolic events has been reported in patients with systemic lupus erythematosus (SLE), but the risks and benefits of primary prophylactic antithrombotic therapy have not been assessed. We measured the clinical benefit of 3 antithrombotic regimens in patients with SLE without antiphospholipid antibodies, with anticardiolipin antibodies, or with lupus anticoagulant. METHODS: A Markov decision analysis was used to evaluate prophylactic aspirin therapy, prophylactic oral anticoagulant therapy, and observation. Input data were obtained by literature review. Clinical practice was simulated in a hypothetical cohort of patients with SLE who had not experienced any previous episode of arterial or venous thromboembolic events. For each strategy, we measured numbers of thromboembolic events prevented and major bleeding episodes induced, and quality-adjusted survival years. RESULTS: Prophylactic aspirin therapy was the preferred strategy in all settings, the number of prevented thrombotic events exceeding that of induced bleeding episodes. In the baseline analysis (40-year-old patients with SLE), the gain in quality-adjusted survival years achieved by prophylactic aspirin compared with observation ranged from 3 months in patients without antiphospholipid antibodies to 11 months in patients with anticardiolipin antibodies or lupus anticoagulant. Prophylactic oral anticoagulant therapy provided better results than prophylactic aspirin only in patients with lupus anticoagulant and an estimated bleeding risk of 1% per year or less. CONCLUSIONS: Prophylactic aspirin should be given to all patients with SLE to prevent both arterial and venous thrombotic manifestations, especially in patients with antiphospholipid antibodies. In selected patients with lupus anticoagulant and a low bleeding risk, prophylactic oral anticoagulant therapy may provide a higher utility.

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Unique Identifier: 99422950 / PubMed Identifier: 10494759

Authors: Douketis JD. Crowther MA. Julian JA. Stewart K. Donovan D. Kaminska EA. Laskin CA. Ginsberg JS.

Institution: Department of Medicine, McMaster University, Hamilton, Canada. jdouket@fhs.mcmaster.ca

Abstract: 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.

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 98235939 / PubMed Identifier: 9576405

Authors: Schulman S. Svenungsson E. Granqvist S.

Institution: Department of Medicine, Karolinska Hospital, Stockholm, Sweden.

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.

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Unique Identifier: 97438304 / PubMed Identifier: 9292793

Authors: al-Sayegh FA. Ensworth S. Huang S. Stein HB. Klinkhoff AV.

Institution: Department of Medicine, University of British Columbia, Vancouver, Canada.

Abstract: OBJECTIVE: To describe the presentation, course, and management of serious hemorrhagic complications of anticoagulant therapy for patients with antiphospholipid syndrome (APS). METHODS: Charts of patients identified with serious bleeding complications from anticoagulation for APS were reviewed. RESULTS: Patients included 6 women and one man with systemic lupus erythematosus (SLE) and one woman with primary APS. One patient had 3 separate hemorrhagic events. There were 6 episodes of subdural hematoma in 5 patients, one episode of pericarditis with tamponade, one episode of hemoptysis, and one episode of ovarian hemorrhage. In 2 patients, symptoms related to hemorrhage were initially attributed to active SLE. Duration of anticoagulation was between one month and 10 years at the time of bleed. International normalized ratio (INR) and prothrombin time were above the intended range in 6/9 episodes. There were no deaths and no permanent sequelae due to bleeding. Anticoagulant therapy was resumed in 6/7 patients. CONCLUSION: The management of APS must include vigilance, patient education, and anticoagulation to maintain the INR between 3 and 3.5. To prevent hemorrhagic complications, low molecular weight heparin is an option that deserves further study.