A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies.

OBJECTIVE To systematically review the efficacy and safety data of different therapeutic approaches in patients with antiphospholipid antibodies (aPL) and thrombosis. METHODS The Medline database and references from selected reports and review articles were used. Randomized controlled trials, prospective and retrospective cohort studies, and subgroup analysis (n > 15) that focused on the secondary thromboprophylaxis in patients with aPL were selected. RESULTS Sixteen studies were selected. Patients with venous events and a single test for aPL showed a low recurrence rate while receiving oral anticoagulation at a target international normalized ratio (INR) of 2.0-3.0. Patients with stroke and a single positive aPL test had no increased risk compared with those without aPL. Recurrence rates in patients with definite antiphospholipid syndrome (APS) and previous venous thromboembolism were lower than in patients with arterial and/or recurrent events, both with and without therapy. Only 3.8% of recurrent events occurred at an actual INR >3.0. Mortality due to recurrent thrombosis was higher than mortality due to bleeding (18 patients versus 1 patient reported). CONCLUSION For patients with definite APS, we recommend prolonged warfarin therapy at a target INR of 2.0-3.0 in APS patients with first venous events and >3.0 for those with recurrent and/or arterial events. For patients with venous thromboembolism or stroke and a single positive aPL test, we recommend further testing to determine if they have a persisting antibody. If they do not, the same therapy as for the general population should be used (warfarin at a target INR of 2.0-3.0 and low-dose aspirin, respectively).

[1]  G. Ruiz-Irastorza,et al.  Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus , 2007, Lupus.

[2]  E. Nutescu,et al.  Warfarin-related outcomes in patients with antiphospholipid antibody syndrome managed in an anticoagulation clinic , 2006, Thrombosis and Haemostasis.

[3]  M. Khamashta,et al.  Antiphospholipid syndrome: treatment controversies , 2006 .

[4]  J. Eikelboom,et al.  Management of antiphospholipid antibody syndrome: a systematic review. , 2006, JAMA.

[5]  Y. Shoenfeld,et al.  International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) , 2006, Journal of thrombosis and haemostasis : JTH.

[6]  G. Guyatt,et al.  Grading strength of recommendations and quality of evidence in clinical guidelines: report from an american college of chest physicians task force. , 2006, Chest.

[7]  E. Silverman,et al.  Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus. , 2005, Blood.

[8]  G. Ruiz-Irastorza,et al.  Stroke and antiphospholipid syndrome: the treatment debate. , 2005, Rheumatology.

[9]  T. Barbui,et al.  A randomized clinical trial of high‐intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS) 1 , 2005, Journal of thrombosis and haemostasis : JTH.

[10]  M. Margaglione,et al.  Bleeding and re-thrombosis in primary antiphospholipid syndrome on oral anticoagulation , 2005, Thrombosis and Haemostasis.

[11]  Giancarlo Agnelli,et al.  Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[12]  J. Rodríguez-Martorell,et al.  Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. , 2004, The Journal of rheumatology.

[13]  R. Sacco,et al.  Antiphospholipid Antibodies and Risk for Recurrent Vascular Events—Reply , 2004 .

[14]  R. Sacco,et al.  Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. , 2004, JAMA.

[15]  G. Ruiz-Irastorza,et al.  High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. , 2004, Archives of internal medicine.

[16]  J. Douketis,et al.  A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. , 2003, The New England journal of medicine.

[17]  S. Levine,et al.  Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002 , 2003, Lupus.

[18]  J. Piette,et al.  Venous thromboembolism in the antiphospholipid syndrome: management guidelines for secondary prophylaxis , 2003, Lupus.

[19]  G. Hughes,et al.  Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5. , 2002, Archives of internal medicine.

[20]  J. Piette,et al.  Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. , 2002, Arthritis and rheumatism.

[21]  B. Feldman,et al.  Longterm anticoagulation is preferable for patients with antiphospholipid antibody syndrome. result of a decision analysis. , 2002, The Journal of rheumatology.

[22]  K. Furie,et al.  A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. , 2001, The New England journal of medicine.

[23]  G. Espinosa,et al.  Clinical study and follow-up of 100 patients withthe antiphospholipid syndrome , 1999 .

[24]  W A Wilson,et al.  International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. , 1999, Arthritis and rheumatism.

[25]  E. Svenungsson,et al.  Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Duration of Anticoagulation Study Group. , 1998, The American journal of medicine.

[26]  J. Emmerich,et al.  Anticardiolipin Antibodies and Recurrent Thromboembolism , 1997, Thrombosis and Haemostasis.

[27]  S. Looney,et al.  A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis. , 1997, Archives of internal medicine.

[28]  M. Khamashta.  Management of Thrombosis in the Antiphospholipid Syndrome , 1996, Lupus.

[29]  Vittorio Pengo,et al.  Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT) , 1996, The Lancet.

[30]  P. Prandoni,et al.  Antiphospholipid Antibodies, Recurrent Thromboembolism, and Intensity of Warfarin Anticoagulation , 1996, Thrombosis and Haemostasis.

[31]  P. Brill-Edwards,et al.  Antiphospholipid antibodies and venous thromboembolism. , 1995, Blood.

[32]  G. Hughes,et al.  The management of thrombosis in the antiphospholipid-antibody syndrome. , 1995, The New England journal of medicine.

[33]  G. Raskob,et al.  Hemorrhagic complications of anticoagulant treatment. , 1992, Chest.

[34]  P. D. de Groot,et al.  Patients with antiphospholipid antibodies and venous thrombosis should receive long term anticoagulant treatment. , 1993, Annals of the rheumatic diseases.

[35]  G. Raskob,et al.  Hemorrhagic complications of anticoagulant treatment. , 2004, Chest.

[36]  M. Rosove,et al.  Antiphospholipid Thrombosis: Clinical Course after the First Thrombotic Event in 70 Patients , 1992, Annals of Internal Medicine.

[37]  Y. Niho,et al.  Clinical importance of persistence of anticardiolipin antibodies in systemic lupus erythematosus. , 1990, Annals of the rheumatic diseases.

[38]  R. Hull,et al.  Antithrombotic therapy for venous thromboembolic disease. , 1986, Chest.