FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

A correction has been published: N Engl J Med 2004;351(2):200.

Previous Volume 349:1133-1138 September 18, 2003 Number 12 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Lockshin, M. D. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article Related Article PubMed Citation

ABSTRACT

Background Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, there are no prospective data to support this approach to thromboprophylaxis.

Methods We performed a randomized, double-blind trial in which patients with antiphospholipid antibodies and previous thrombosis were assigned to receive enough warfarin to achieve an INR of 2.0 to 3.0 (moderate intensity) or 3.1 to 4.0 (high intensity). Our objective was to show that high-intensity warfarin was more effective in preventing thrombosis than moderate-intensity warfarin.

Results A total of 114 patients were enrolled in the study and followed for a mean of 2.7 years. Recurrent thrombosis occurred in 6 of 56 patients (10.7 percent) assigned to receive high-intensity warfarin and in 2 of 58 patients (3.4 percent) assigned to receive moderate-intensity warfarin (hazard ratio for the high-intensity group, 3.1; 95 percent confidence interval, 0.6 to 15.0). Major bleeding occurred in three patients assigned to receive high-intensity warfarin and four patients assigned to receive moderate-intensity warfarin (hazard ratio, 1.0; 95 percent confidence interval, 0.2 to 4.8).

Conclusions High-intensity warfarin was not superior to moderate-intensity warfarin for thromboprophylaxis in patients with antiphospholipid antibodies and previous thrombosis. The low rate of recurrent thrombosis among patients in whom the target INR was 2.0 to 3.0 suggests that moderate-intensity warfarin is appropriate for patients with the antiphospholipid antibody syndrome.

Source Information

From the Departments of Medicine (M.A.C., J.S.G., J. Denburg, J.H., J. Douketis, C.K.) and Clinical Epidemiology and Biostatistics (J.J., L.C., W.Y., M.G.), McMaster University, Hamilton, Ont.; the Department of Medicine (C.L., P.F., W.G.) and the Undergraduate Medical Program (S.W.), University of Toronto, Toronto; the Department of Medicine, Dalhousie University, Halifax, N.S. (D.A.); the Department of Medicine, McGill University, Montreal (A.C.); the Department of Medicine, University of Ottawa, Ottawa, Ont. (M.F.); and the Department of Medicine, University of Western Ontario, London, Ont. (M.J.K.) — all in Canada; and the Department of Medicine, Northwestern University, Chicago (D.G.).

Address reprint requests to Dr. Crowther at St. Joseph's Hospital, Rm. L208, 50 Charlton Ave. E., Hamilton, ON L8N 4A6, Canada, or at crowthrm{at}mcmaster.ca.

Full Text of this Article

Related Letters:

Warfarin Prophylaxis in the Antiphospholipid Antibody Syndrome
Paul N., Kosinski C. M., Gelber A. C., Saleh A. S., Stern S. D., Crowther M., Ginsberg J.
Extract | Full Text | PDF  
N Engl J Med 2003; 349:2568-2570, Dec 25, 2003. Correspondence

This article has been cited by other articles:

• Giannakopoulos, B., Krilis, S. A. (2009). How I treat the antiphospholipid syndrome. Blood 114: 2020-2030 [Abstract] [Full Text]  
• Tan, B., Thong, B., Shivananda, S, Han, W., Chng, H. (2009). Clinical manifestations and outcomes of antithrombotic treatment of the Tan Tock Seng Hospital Singapore antiphospholipid syndrome cohort. Lupus 18: 752-758 [Abstract]  
• Cios, D. A., Baker, W. L., Sander, S. D., Phung, O. J., Coleman, C. I. (2009). Evaluating the impact of study-level factors on warfarin control in U.S.-based primary studies: A meta-analysis. Am J Health Syst Pharm 66: 916-925 [Abstract] [Full Text]  
• Zhu, T., Martinez, I., Emmerich, J. (2009). Venous Thromboembolism: Risk Factors for Recurrence. Arterioscler. Thromb. Vasc. Bio. 29: 298-310 [Abstract] [Full Text]  
• Farmer-Boatwright, M. K., Roubey, R. A.S. (2009). Venous Thrombosis in the Antiphospholipid Syndrome. Arterioscler. Thromb. Vasc. Bio. 29: 321-325 [Abstract] [Full Text]  
• Giannakopoulos, B., Passam, F., Ioannou, Y., Krilis, S. A. (2009). How we diagnose the antiphospholipid syndrome. Blood 113: 985-994 [Abstract] [Full Text]  
• Sakamoto, S., Akutsu, K., Kawase, K., Takada, T., Seyama, H., Takahashi, J., Miyamoto, S., Nonogi, H., Takeshita, S. (2009). Simultaneous Presentations of Deep Vein Thrombosis and Cerebral Sinus Thrombosis in a Case of Primary Antiphospholipid Syndrome. ANGIOLOGY 59: 765-768 [Abstract]  
• Chan, M. Y., Andreotti, F., Becker, R. C. (2008). Hypercoagulable States in Cardiovascular Disease. Circulation 118: 2286-2297 [Full Text]  
• Wu, H., Birmingham, D. J., Rovin, B., Hackshaw, K. V., Haddad, N., Haden, D., Yu, C.-Y., Hebert, L. A. (2008). D-Dimer Level and the Risk for Thrombosis in Systemic Lupus Erythematosus. CJASN 3: 1628-1636 [Abstract] [Full Text]  
• Avcin, T., Cimaz, R., Silverman, E. D., Cervera, R., Gattorno, M., Garay, S., Berkun, Y., Sztajnbok, F. R., Silva, C. A., Campos, L. M., Saad-Magalhaes, C., Rigante, D., Ravelli, A., Martini, A., Rozman, B., Meroni, P. L. (2008). Pediatric Antiphospholipid Syndrome: Clinical and Immunologic Features of 121 Patients in an International Registry. Pediatrics 122: e1100-e1107 [Abstract] [Full Text]  
• Rand, J. H., Wu, X.-X., Quinn, A. S., Chen, P. P., Hathcock, J. J., Taatjes, D. J. (2008). Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-{beta}2-glycoprotein I complexes to phospholipid bilayers. Blood 112: 1687-1695 [Abstract] [Full Text]  
• Ansell, J., Hirsh, J., Hylek, E., Jacobson, A., Crowther, M., Palareti, G. (2008). Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133: 160S-198S [Abstract] [Full Text]  
• Schulman, S., Beyth, R. J., Kearon, C., Levine, M. N. (2008). Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133: 257S-298S [Abstract] [Full Text]  
• Kearon, C., Kahn, S. R., Agnelli, G., Goldhaber, S., Raskob, G. E., Comerota, A. J. (2008). Antithrombotic Therapy for Venous Thromboembolic Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133: 454S-545S [Abstract] [Full Text]  
• Horner, K. E., Phillips, B. B., Newkirk, E., McDanel, D. L., Kaboli, P. (2008). Evaluation of anticoagulation in patients with antiphospholipid syndrome. Am J Health Syst Pharm 65: 964-967 [Abstract] [Full Text]  
• Lockshin, M., Derksen, R. (2008). New developments in lupus-associated antiphospholipid syndrome. Lupus 17: 443-446 [Abstract]  
• Bertsias, G, Ioannidis, J P A, Boletis, J, Bombardieri, S, Cervera, R, Dostal, C, Font, J, Gilboe, I M, Houssiau, F, Huizinga, T, Isenberg, D, Kallenberg, C G M, Khamashta, M, Piette, J C, Schneider, M, Smolen, J, Sturfelt, G, Tincani, A, van Vollenhoven, R, Gordon, C, Boumpas, D T (2008). EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 67: 195-205 [Abstract] [Full Text]  
• Swigris, J. J., Fischer, A., Gilles, J., Meehan, R. T., Brown, K. K. (2008). Pulmonary and Thrombotic Manifestations of Systemic Lupus Erythematosus. Chest 133: 271-280 [Abstract] [Full Text]  
• Goldenberg, N. A. (2008). Thrombophilia States and Markers of Coagulation Activation in the Prediction of Pediatric Venous Thromboembolic Outcomes: A Comparative Analysis with Respect to Adult Evidence. ASH Education Book 2008: 236-244 [Abstract] [Full Text]  
• Rose, A., Sajkov, D. (2007). A 29-Year-Old Man With Pulmonary Complications of a Thrombotic Disorder. Chest 132: 2008-2011 [Full Text]  
• Garcia, D. A., Khamashta, M. A., Crowther, M. A. (2007). How we diagnose and treat thrombotic manifestations of the antiphospholipid syndrome: a case-based review. Blood 110: 3122-3127 [Abstract] [Full Text]  
• Galli, M., Borrelli, G., Jacobsen, E. M., Marfisi, R. M., Finazzi, G., Marchioli, R., Wisloff, F., Marziali, S., Morboeuf, O., Barbui, T. (2007). Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood 110: 1178-1183 [Abstract] [Full Text]  
• Avcin, T., Silverman, E. (2007). Review: Antiphospholipid antibodies in pediatric systemic lupus erythematosus and the antiphospholipid syndrome. Lupus 16: 627-633 [Abstract]  
• Krause, I, Leibovici, L, Blank, M, Shoenfeld, Y (2007). Clusters of disease manifestations in patients with antiphospholipid syndrome demonstrated by factor analysis. Lupus 16: 176-180 [Abstract]  
• Abu Romeh, I. S., Chhatriwalla, A. K., Atik, F. A., Bhatt, D. L., Navia, J. L. (2007). Myocardial Infarction Secondary to a Coronary Ostial Thrombus in Antiphospholipid Syndrome. Ann. Thorac. Surg. 83: 1170-1171 [Abstract] [Full Text]  
• Tarr, T, Lakos, G, Bhattoa, H P, Shoenfeld, Y, Szegedi, G, Kiss, E (2007). Analysis of risk factors for the development of thrombotic complications in antiphospholipid antibody positive lupus patients. Lupus 16: 39-45 [Abstract]  
• Rand, J. H. (2007). The Antiphospholipid Syndrome. ASH Education Book 2007: 136-142 [Abstract] [Full Text]  
• Scarvelis, D., Wells, P. S. (2006). Diagnosis and treatment of deep-vein thrombosis.. CMAJ 175: 1087-1092 [Abstract] [Full Text]  
• Wahl, D., Regnault, V. (2006). Treatment of antiphospholipid antibody syndrome.. JAMA 296: 42-43 [Full Text]  
• Ostertag, M V., Liu, X, Henderson, V, Pierangeli, S S (2006). A peptide that mimics the Vth region of {beta}2glycoprotein I reverses antiphospholipid-mediated thrombosis in mice. Lupus 15: 358-365 [Abstract]  
• Vora, S. K., Asherson, R. A., Erkan, D. (2006). Catastrophic Antiphospholipid Syndrome. J Intensive Care Med 21: 144-159 [Abstract]  
• van Walraven, C., Jennings, A., Oake, N., Fergusson, D., Forster, A. J. (2006). Effect of Study Setting on Anticoagulation Control: A Systematic Review and Metaregression. Chest 129: 1155-1166 [Abstract] [Full Text]  
• D'Cruz, D. P (2006). Systemic lupus erythematosus.. BMJ 332: 890-894 [Full Text]  
• Ingegnoli, F, Soldi, A, Meani, L, Zeni, S, Fantini, F (2006). Primary antiphospholipid syndrome associated with small aorta syndrome: a case report. Lupus 15: 236-239 [Abstract]  
• Sacco, R. L., Adams, R., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Schwamm, L. H., Tomsick, T. (2006). Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.. Circulation 113: e409-e449 [Abstract] [Full Text]  
• Bertolaccini, M L, Khamashta, M A (2006). Laboratory diagnosis and management challenges in the antiphospholipid syndrome. Lupus 15: 172-178 [Abstract]  
• Lim, W., Crowther, M. A., Eikelboom, J. W. (2006). Management of Antiphospholipid Antibody Syndrome: A Systematic Review. JAMA 295: 1050-1057 [Abstract] [Full Text]  
• Sacco, R. L., Adams, R., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Schwamm, L. H., Tomsick, T. (2006). Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.. Stroke 37: 577-617 [Abstract] [Full Text]  
• Statkute, L., Traynor, A., Oyama, Y., Yaung, K., Verda, L., Krosnjar, N., Burt, R. K. (2005). Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation. Blood 106: 2700-2709 [Abstract] [Full Text]  
• Ruiz-Irastorza, G., Khamashta, M. A. (2005). Stroke and antiphospholipid syndrome: the treatment debate. Rheumatology (Oxford) 44: 971-974 [Abstract] [Full Text]  
• Turiel, M., Sarzi-Puttini, P., Peretti, R., Rossi, E., Atzeni, F., Parsons, W., Doria, A. (2005). Thrombotic Risk Factors In Primary Antiphospholipid Syndrome: A 5-Year Prospective Study. Stroke 36: 1490-1494 [Abstract] [Full Text]  
• Quenby, S., Farquharson, R.G., Dawood, F., Hughes, A.M., Topping, J. (2005). Recurrent miscarriage and long-term thrombosis risk: a case-control study. Hum Reprod 20: 1729-1732 [Abstract] [Full Text]  
• Andreotti, F., Becker, R. C. (2005). Atherothrombotic Disorders: New Insights From Hematology. Circulation 111: 1855-1863 [Full Text]  
• Letang, E, Rodriguez-Carballeira, M, Muchart, J, Torres, J, de Echaguen, A O., Garau, J (2005). Letter to the Editor. Lupus 14: 336-337  
• Ortel, T. L. (2005). Thrombosis and the Antiphospholipid Syndrome. ASH Education Book 2005: 462-468 [Abstract] [Full Text]  
• Hellmann, D. B. (2004). Update in Rheumatology. ANN INTERN MED 141: 801-804 [Full Text]  
• Wittkowsky, A. K. (2004). Anticoagulation in Hypercoagulable Conditions: Special Considerations in the Treatment and Prevention of Venous Thromboembolism. Journal of Pharmacy Practice 17: 308-316 [Abstract]  
• Ansell, J., Hirsh, J., Poller, L., Bussey, H., Jacobson, A., Hylek, E. (2004). The Pharmacology and Management of the Vitamin K Antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 204S-233S [Abstract] [Full Text]  
• Levine, M. N., Raskob, G., Beyth, R. J., Kearon, C., Schulman, S. (2004). Hemorrhagic Complications of Anticoagulant Treatment: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 287S-310S [Abstract] [Full Text]  
• Buller, H. R., Agnelli, G., Hull, R. D., Hyers, T. M., Prins, M. H., Raskob, G. E. (2004). Antithrombotic Therapy for Venous Thromboembolic Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 401S-428S [Abstract] [Full Text]  
• Kearon, C. (2004). Long-Term Management of Patients After Venous Thromboembolism. Circulation 110: I-10-I-18 [Abstract] [Full Text]  
• Augustinos, P., Ouriel, K. (2004). Invasive Approaches to Treatment of Venous Thromboembolism. Circulation 110: I-27-I-34 [Abstract] [Full Text]  
• Greaves, M. (2004). Masterclass series in peripheral arterial disease: Acquired thrombophilia. Vasc Med 9: 215-218  
• Levine, S. R., Brey, R. L., Tilley, B. C., Triplett, D. A., Thompson, J. L. P., Sacco, R. L., Mohr, J. P., for the APASS Investigators, (2004). Antiphospholipid Antibodies and Risk for Recurrent Vascular Events--Reply. JAMA 291: 2702-2703 [Full Text]  
• Ozturk, M. A., Haznedaroglu, I. C., Turgut, M., Goker, H. (2004). Current Debates in Antiphospholipid Syndrome: The Acquired Antibody-Mediated Thrombophilia. CLIN APPL THROMB HEMOST 10: 89-126 [Abstract]  
• Wilson, S. E., Watson, H. G., Crowther, M. A. (2004). Low-dose oral vitamin K therapy for the management of asymptomatic patients with elevated international normalized ratios: a brief review. CMAJ 170: 821-824 [Abstract] [Full Text]  
• (2004). Additional articles abstracted in ACP Journal Club. Evid. Based Med. 9: 35-35 [Full Text]  
• APASS Investigators, (2004). Antiphospholipid Antibodies and Subsequent Thrombo-occlusive Events in Patients With Ischemic Stroke. JAMA 291: 576-584 [Abstract] [Full Text]  
• Nielson, C, Wingete, D (2004). Intensive care and invasive ventilation in the elderly patient, implications of chronic lung disease and comorbidities. Chronic Respiratory Disease 1: 43-54 [Abstract]  
• Paul, N., Kosinski, C. M., Gelber, A. C., Saleh, A. S., Stern, S. D., Crowther, M., Ginsberg, J. (2003). Warfarin Prophylaxis in the Antiphospholipid Antibody Syndrome. NEJM 349: 2568-2570 [Full Text]  
• (2003). High-Intensity Warfarin -- Unwarranted in Patients with Antiphospholipid Antibodies?. Journal Watch Cardiology 2003: 3-3 [Full Text]  
• (2003). Antiphospholipid Antibody Syndrome: Is High-Intensity Warfarin Necessary?. JWatch General 2003: 2-2 [Full Text]  
• Lockshin, M. D., Erkan, D. (2003). Treatment of the Antiphospholipid Syndrome. NEJM 349: 1177-1179 [Full Text]  
• Warkentin, T. E., Aird, W. C., Rand, J. H. (2003). Platelet-Endothelial Interactions: Sepsis, HIT, and Antiphospholipid Syndrome. ASH Education Book 2003: 497-519 [Abstract] [Full Text]