UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Treatment of antiphospholipid syndrome

Authors
Peter H Schur, MD
Andre A Kaplan, MD
Section Editor
David S Pisetsky, MD, PhD
Deputy Editors
Monica Ramirez Curtis, MD, MPH
Jennifer S Tirnauer, MD

INTRODUCTION

Antiphospholipid antibody syndrome (APS) is defined by two major components:

Presence in the serum of at least one type of autoantibody known as an antiphospholipid antibody (aPL). The aPL are directed against phospholipid-binding plasma proteins.

The occurrence of at least one of the following clinical features: venous or arterial thromboses and/or pregnancy morbidity.

Although most of the clinical manifestations of APS can occur in other disease populations, in patients with APS, they occur by definition in the context of aPL. aPL are directed against serum proteins bound to anionic phospholipids and may be detected as:

Lupus anticoagulants (LA)

                                            

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Aug 02 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Segal JB, Streiff MB, Hofmann LV, et al. Management of venous thromboembolism: a systematic review for a practice guideline. Ann Intern Med 2007; 146:211.
  2. Koopman MM, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med 1996; 334:682.
  3. Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334:677.
  4. Boccalon H, Elias A, Chalé JJ, et al. Clinical outcome and cost of hospital vs home treatment of proximal deep vein thrombosis with a low-molecular-weight heparin: the Vascular Midi-Pyrenees study. Arch Intern Med 2000; 160:1769.
  5. O'Shaughnessy D, Miles J, Wimperis J. UK patients with deep-vein thrombosis can be safely treated as out-patients. QJM 2000; 93:663.
  6. Grau E, Tenias JM, Real E, et al. Home treatment of deep venous thrombosis with low molecular weight heparin: Long-term incidence of recurrent venous thromboembolism. Am J Hematol 2001; 67:10.
  7. Dunn A, Bioh D, Beran M, et al. Effect of intravenous heparin administration on duration of hospitalization. Mayo Clin Proc 2004; 79:159.
  8. Douketis JD. Treatment of deep vein thrombosis: what factors determine appropriate treatment? Can Fam Physician 2005; 51:217.
  9. Ansell J, Hirsh J, Poller L, et al. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:204S.
  10. Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337:688.
  11. Crowther MA, Ginsberg JS, Julian J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003; 349:1133.
  12. Finazzi G, Marchioli R, Brancaccio V, 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). J Thromb Haemost 2005; 3:848.
  13. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e152S.
  14. Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992; 117:303.
  15. Khamashta MA, Cuadrado MJ, Mujic F, et al. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332:993.
  16. Barbhaiya M, Erkan D. Primary thrombosis prophylaxis in antiphospholipid antibody-positive patients: where do we stand? Curr Rheumatol Rep 2011; 13:59.
  17. Bick RL. Antiphospholipid thrombosis syndromes. Hematol Oncol Clin North Am 2003; 17:115.
  18. Chighizola CB, Moia M, Meroni PL. New oral anticoagulants in thrombotic antiphospholipid syndrome. Lupus 2014; 23:1279.
  19. Erkan D, Harrison MJ, Levy R, et al. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum 2007; 56:2382.
  20. Win K, Rodgers GM. New oral anticoagulants may not be effective to prevent venous thromboembolism in patients with antiphospholipid syndrome. Am J Hematol 2014; 89:1017.
  21. Erkan D, Yazici Y, Peterson MG, et al. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford) 2002; 41:924.
  22. Tektonidou MG, Laskari K, Panagiotakos DB, Moutsopoulos HM. Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies. Arthritis Rheum 2009; 61:29.
  23. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69:20.
  24. Jung H, Bobba R, Su J, et al. The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus. Arthritis Rheum 2010; 62:863.
  25. Mok MY, Chan EY, Fong DY, et al. Antiphospholipid antibody profiles and their clinical associations in Chinese patients with systemic lupus erythematosus. J Rheumatol 2005; 32:622.
  26. Petri M. Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort. Lupus 2000; 9:170.
  27. Edwards MH, Pierangeli S, Liu X, et al. Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice. Circulation 1997; 96:4380.
  28. Espinola RG, Pierangeli SS, Gharavi AE, Harris EN. Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb Haemost 2002; 87:518.
  29. Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus 2011; 20:206.
  30. Vianna JL, Khamashta MA, Ordi-Ros J, et al. Comparison of the primary and secondary antiphospholipid syndrome: a European Multicenter Study of 114 patients. Am J Med 1994; 96:3.
  31. Hereng T, Lambert M, Hachulla E, et al. Influence of aspirin on the clinical outcomes of 103 anti-phospholipid antibodies-positive patients. Lupus 2008; 17:11.
  32. Ruffatti A, Del Ross T, Ciprian M, et al. Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study. Ann Rheum Dis 2009; 68:397.
  33. Shah NM, Khamashta MA, Atsumi T, Hughes GR. Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients. Lupus 1998; 7:3.
  34. Somers E, Magder LS, Petri M. Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol 2002; 29:2531.
  35. Alarcón-Segovia D, Boffa MC, Branch W, et al. Prophylaxis of the antiphospholipid syndrome: a consensus report. Lupus 2003; 12:499.
  36. Erkan D, Merrill JT, Yazici Y, et al. High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum 2001; 44:1466.
  37. Wahl DG, Bounameaux H, de Moerloose P, Sarasin FP. Prophylactic antithrombotic therapy for patients with systemic lupus erythematosus with or without antiphospholipid antibodies: do the benefits outweigh the risks? A decision analysis. Arch Intern Med 2000; 160:2042.
  38. Ruiz-Irastorza G, Khamashta MA. The treatment of antiphospholipid syndrome: a harmonic contrast. Best Pract Res Clin Rheumatol 2007; 21:1079.
  39. Cuadrado MJ, Bertolaccini ML, Seed PT, et al. Low-dose aspirin vs low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial in patients positive for antiphospholipid antibodies (ALIWAPAS). Rheumatology (Oxford) 2014; 53:275.
  40. Ruiz-Irastorza G, Hunt BJ, Khamashta MA. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum 2007; 57:1487.
  41. Schulman S, Svenungsson E, Granqvist S. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Duration of Anticoagulation Study Group. Am J Med 1998; 104:332.
  42. Sacco RL, Adams R, Albers G, et al. 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 2006; 37:577.
  43. Muscal E, Brey RL. Neurologic manifestations of the antiphospholipid syndrome: integrating molecular and clinical lessons. Curr Rheumatol Rep 2008; 10:67.
  44. Zavaleta NE, Montes RM, Soto ME, et al. Primary antiphospholipid syndrome: a 5-year transesophageal echocardiographic followup study. J Rheumatol 2004; 31:2402.
  45. Lockshin M, Tenedios F, Petri M, et al. Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report. Lupus 2003; 12:518.
  46. Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e576S.
  47. Atsumi T, Furukawa S, Amengual O, Koike T. Antiphospholipid antibody associated thrombocytopenia and the paradoxical risk of thrombosis. Lupus 2005; 14:499.
  48. Leuzzi RA, Davis GH, Cowchock FS, et al. Management of immune thrombocytopenic purpura associated with the antiphospholipid antibody syndrome. Clin Exp Rheumatol 1997; 15:197.
  49. Petri M. Pathogenesis and treatment of the antiphospholipid antibody syndrome. Med Clin North Am 1997; 81:151.
  50. Kavanaugh A. Danazol therapy in thrombocytopenia associated with the antiphospholipid antibody syndrome. Ann Intern Med 1994; 121:767.
  51. Alarcón-Segovia D, Sánchez-Guerrero J. Correction of thrombocytopenia with small dose aspirin in the primary antiphospholipid syndrome. J Rheumatol 1989; 16:1359.
  52. Durand JM, Lefevre P, Kaplanski G, et al. Correction of thrombocytopenia with dapsone in the primary antiphospholipid syndrome. J Rheumatol 1993; 20:1777.
  53. Suarez IM, Diaz RA, Aguayo Canela D, Pujol de la Llave E. Correction of severe thrombocytopenia with chloroquine in the primary antiphospholipid syndrome. Lupus 1996; 5:81.
  54. Erkan D, Leibowitz E, Berman J, Lockshin MD. Perioperative medical management of antiphospholipid syndrome: hospital for special surgery experience, review of literature, and recommendations. J Rheumatol 2002; 29:843.
  55. Erkan D, Cervera R, Asherson RA. Catastrophic antiphospholipid syndrome: where do we stand? Arthritis Rheum 2003; 48:3320.
  56. Bucciarelli S, Espinosa G, Cervera R, et al. Mortality in the catastrophic antiphospholipid syndrome: causes of death and prognostic factors in a series of 250 patients. Arthritis Rheum 2006; 54:2568.
  57. Cervera R, Rodríguez-Pintó I, Colafrancesco S, et al. 14th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome. Autoimmun Rev 2014; 13:699.
  58. Lockshin MD, Erkan D. Treatment of the antiphospholipid syndrome. N Engl J Med 2003; 349:1177.
  59. Cervera R, Rodríguez-Pintó I, G Espinosa on behalf of the Task Force on Catastrophic Antiphospholipid Syndrome. Catastrophic antiphospholipid syndrome: task force report summary. Lupus 2014; 23:1283.
  60. Cervera R. Update on the diagnosis, treatment, and prognosis of the catastrophic antiphospholipid syndrome. Curr Rheumatol Rep 2010; 12:70.
  61. Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 2001; 80:355.
  62. Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore) 1998; 77:195.
  63. Zar T, Kaplan AA. Predictable removal of anticardiolipin antibody by therapeutic plasma exchange (TPE) in catastrophic antiphospholipid antibody syndrome (CAPS). Clin Nephrol 2008; 70:77.
  64. Shapira I, Andrade D, Allen SL, Salmon JE. Brief report: induction of sustained remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab. Arthritis Rheum 2012; 64:2719.
  65. Rubenstein E, Arkfeld DG, Metyas S, et al. Rituximab treatment for resistant antiphospholipid syndrome. J Rheumatol 2006; 33:355.
  66. Berman H, Rodríguez-Pintó I, Cervera R, et al. Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab. Autoimmun Rev 2013; 12:1085.
  67. Strakhan M, Hurtado-Sbordoni M, Galeas N, et al. 36-year-old female with catastrophic antiphospholipid syndrome treated with eculizumab: a case report and review of literature. Case Rep Hematol 2014; 2014:704371.
  68. Kronbichler A, Frank R, Kirschfink M, et al. Efficacy of eculizumab in a patient with immunoadsorption-dependent catastrophic antiphospholipid syndrome: a case report. Medicine (Baltimore) 2014; 93:e143.
  69. Cervera R, CAPS Registry Project Group. Catastrophic antiphospholipid syndrome (CAPS): update from the 'CAPS Registry'. Lupus 2010; 19:412.
  70. Erkan D, Asherson RA, Espinosa G, et al. Long term outcome of catastrophic antiphospholipid syndrome survivors. Ann Rheum Dis 2003; 62:530.
  71. Moll S, Ortel TL. Monitoring warfarin therapy in patients with lupus anticoagulants. Ann Intern Med 1997; 127:177.
  72. Hylek EM, Heiman H, Skates SJ, et al. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 1998; 279:657.
  73. Robert A, Le Querrec A, Delahousse B, et al. Control of oral anticoagulation in patients with the antiphospholipid syndrome--influence of the lupus anticoagulant on International Normalized Ratio. Groupe Méthodologie en Hémostase du Groupe d'Etudes sur l'Hémostases et la Thrombose. Thromb Haemost 1998; 80:99.
  74. Kasthuri RS, Roubey RA. Warfarin and the antiphospholipid syndrome: does one size fit all? Arthritis Rheum 2007; 57:1346.
  75. Lawrie AS, Purdy G, Mackie IJ, Machin SJ. Monitoring of oral anticoagulant therapy in lupus anticoagulant positive patients with the anti-phospholipid syndrome. Br J Haematol 1997; 98:887.
  76. Douketis JD, Crowther MA, Julian JA, et al. The effects of low-intensity warfarin on coagulation activation in patients with antiphospholipid antibodies and systemic lupus erythematosus. Thromb Haemost 1999; 82:1028.
  77. Tripodi A, Chantarangkul V, Clerici M, et al. Laboratory control of oral anticoagulant treatment by the INR system in patients with the antiphospholipid syndrome and lupus anticoagulant. Results of a collaborative study involving nine commercial thromboplastins. Br J Haematol 2001; 115:672.
  78. Lockshin MD. Antiphospholipid antibody. Babies, blood clots, biology. JAMA 1997; 277:1549.
  79. Ruiz-Irastorza G, Khamashta MA, Hunt BJ, 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. Arch Intern Med 2002; 162:1164.
  80. Statkute L, Traynor A, Oyama Y, et al. Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation. Blood 2005; 106:2700.
  81. Kumar D, Roubey RA. Use of rituximab in the antiphospholipid syndrome. Curr Rheumatol Rep 2010; 12:40.
  82. Erkan D, Vega J, Ramón G, et al. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum 2013; 65:464.
  83. Keswani SC, Chauhan N. Antiphospholipid syndrome. J R Soc Med 2002; 95:336.
  84. Cervera R, Khamashta MA, Shoenfeld Y, et al. Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2009; 68:1428.