Skip to main content

Advertisement

Management of the antiphospholipid syndrome

Abstract

Antiphospholipid syndrome (APS) is characterized by recurrent venous or arterial thromboses, fetal losses and thrombocytopenia in the presence of antiphospholipid antibodies, namely lupus anticoagulant, anticardiolipin antibodies or antibodies directed to various proteins, mainly β2 glycoprotein I, or all three. There is consensus in treating patients with APS and first venous thrombosis with oral anticoagulation to a target international normalized ratio (INR) of 2.0–3.0. A recent systematic review recommended a target INR of >3.0 in those patients with APS and arterial thrombosis. The approach in women with obstetric manifestations of APS is based on the use of aspirin plus heparin. The best treatment for patients with the catastrophic variant of the APS is a combination of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins.

References

  1. 1.

    Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306

  2. 2.

    Asherson RA, Khamashta MA, Ordi-Ros J et al (1989) The “primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 68:366–374

  3. 3.

    Cervera R (2008) Lessons from the “Euro-Phospholipid” project. Autoimmun Rev 7:174–178

  4. 4.

    Asherson RA (1992) The catastrophic antiphospholipid syndrome. J Rheumatol 19:508–512

  5. 5.

    Cervera R, Piette JC, Font J et al (2002) Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 46:1019–1027

  6. 6.

    Bucciarelli S, Espinosa G, Cervera R et al (2006) Mortality in the catastrophic antiphospholipid syndrome: causes of death and prognostic factors in a series of 250 patients. Arthritis Rheum 54:2568–2576

  7. 7.

    Shah NM, Khamashta MA, Atsumi T et al (1998) Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients. Lupus 7:3–6

  8. 8.

    Finazzi G, Brancaccio V, Moia M et al (1996) Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. Am J Med 100:530–536

  9. 9.

    Girón-González JA, García del Rio E, Rodríguez C et al (2004) Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol 31:1560–1567

  10. 10.

    Somers E, Magder LS, Petri M (2002) Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol 29:2531–2536

  11. 11.

    Forastiero R, Martinuzzo M, Pombo G et al (2005) A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis. J Thromb Haemost 3:1231–1238

  12. 12.

    Erkan D, Harrison MJ, Levy R et al (2007) Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum 56:2382–2391

  13. 13.

    Gerosa M, Chighizola C, Meroni PL (2008) Aspirin in asymptomatic patients with confirmed positivity of antiphospholipid antibodies? Yes (in some cases). Intern Emerg Med 3:201–203

  14. 14.

    Erkan D (2006) Lupus and thrombosis. J Rheumatol 33:1715–1717

  15. 15.

    Wahl DG, Bounameaux H, de Moerloose P et al (2000) 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 160:2042–2048

  16. 16.

    Ruiz-Irastorza G, Egurbide MV, Pijoan JI et al (2006) Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 15:577–583

  17. 17.

    Erkan D, Yazici Y, Peterson MG et al (2002) A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford) 41:924–929

  18. 18.

    Erkan D, Merrill JT, Yazici Y et al (2001) High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum 44:1466–1467

  19. 19.

    Tincani A, Taglietti M, Biasini C et al (2002) Thromboembolic events after fetal loss in patients with antiphospholipid syndrome: comment on the article by Erkan et al. Arthritis Rheum 46:1126–1127

  20. 20.

    Ruffatti A, Del Ross T, Ciprian M et al (2009) Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicenter retrospective follow-up study. Ann Rheum Dis 68:397–399

  21. 21.

    Wahl DG, Guillemin F, de Maistre E et al (1997) Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus -a meta-analysis. Lupus 6:467–473

  22. 22.

    Wahl DG, Guillemin F, de Maistre E et al (1998) Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus 7:15–22

  23. 23.

    Galli M, Luciani D, Bertolini G et al (2003) Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 101:1827–1832

  24. 24.

    Turiel M, Sarzi-Puttini P, Peretti R et al (2005) Thrombotic risk factors in primary antiphospholipid syndrome: a 5-year prospective study. Stroke 36:1490–1494

  25. 25.

    Galli M, Luciani D, Bertolini G et al (2003) Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 102:2717–2723

  26. 26.

    Ruiz-Irastorza G, Hunt BJ, Khamashta MA (2007) A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum 57:1487–1495

  27. 27.

    Lim W, Crowther MA, Eikelboom JW (2006) Management of antiphospholipid antibody syndrome: a systematic review. JAMA 295:1050–1057

  28. 28.

    Rosove MH, Brewer PM (1992) Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 117:303–308

  29. 29.

    Derksen RH, de Groot PG, Kater L et al (1993) Patients with antiphospholipid antibodies and venous thrombosis should receive long term anticoagulant treatment. Ann Rheum Dis 52:689–692

  30. 30.

    Khamashta MA, Cuadrado MJ, Mujic F et al (1995) The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 332:993–997

  31. 31.

    Krnic-Barrie S, O’Connor CR, Looney SW et al (1997) A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis. Arch Intern Med 157:2101–2108

  32. 32.

    Muñoz-Rodríguez FJ, Font J, Cervera R et al (1999) Clinical study and follow-up of 100 patients with the antiphospholipid syndrome. Semin Arthritis Rheum 29:182–190

  33. 33.

    Ruiz-Irastorza G, Khamashta MA, Hunt BJ et al (2002) 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 162:1164–1169

  34. 34.

    Ames PR, Ciampa A, Margaglione M et al (2005) Bleeding and re-thrombosis in primary antiphospholipid syndrome on oral anticoagulation: an 8-year longitudinal comparison with mitral valve replacement and inherited thrombophilia. Thromb Haemost 93:694–699

  35. 35.

    Wittkowsky AK, Downing J, Blackburn J et al (2006) Warfarin-related outcomes in patients with antiphospholipid antibody syndrome managed in an anticoagulation clinic. Thromb Haemost 96:137–141

  36. 36.

    Ginsberg JS, Wells PS, Brill-Edwards P et al (1995) Antiphospholipid antibodies and venous thromboembolism. Blood 86:3685–3691

  37. 37.

    Prandoni P, Simioni P, Girolami A (1996) Antiphospholipid antibodies, recurrent thromboembolism, and intensity of warfarin anticoagulation. Thromb Haemost 75:859

  38. 38.

    Rance A, Emmerich J, Fiessinger JN (1997) Anticardiolipin antibodies and recurrent thromboembolism. Thromb Haemost 77:221–222

  39. 39.

    Schulman S, Svenungsson E, Granqvist S (1998) 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 104:332–338

  40. 40.

    Crowther MA, Ginsberg JS, Julian J et al (2003) A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 349:1133–1138

  41. 41.

    Finazzi G, Marchioli R, Brancaccio V et al (2005) 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 3:848–853

  42. 42.

    Ho WK, Hankey GJ, Quinlan DJ et al (2006) Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med 166:729–736

  43. 43.

    Hron G, Eichinger S, Weltermann A et al (2006) Family history for venous thromboembolism and the risk for recurrence. Am J Med 119:50–53

  44. 44.

    Auerbach AD, Sanders GD, Hambleton J (2004) Cost-effectiveness of testing for hypercoagulability and effects on treatment strategies in patients with deep vein thrombosis. Am J Med 116:816–828

  45. 45.

    Straczek C, Alhenc-Gelas M, Aubry ML et al (2005) Genetic variation at the estrogen receptor alpha locus in relation to venous thromboembolism risk among postmenopausal women. J Thromb Haemost 3:1535–1537

  46. 46.

    Straczek C, Oger E, Yon de Jonage-Canonico MB et al (2005) Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation 112:3495–3500

  47. 47.

    Chopra N, Koren S, Greer WL et al (2002) Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with antiphospholipid antibodies. J Rheumatol 29:1683–1688

  48. 48.

    Galli M, Finazzi G, Duca F et al (2000) The G1691 → A mutation of factor V, but not the G20210 → A mutation of factor II or the C677 → T mutation of methylenetetrahydrofolate reductase genes, is associated with venous thrombosis in patients with lupus anticoagulants. Br J Haematol 108:865–870

  49. 49.

    Galli M, Borrelli G, Jacobsen EM et al (2007) Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood 110:1178–1183

  50. 50.

    Martínez-Berriotxoa A, Ruiz-Irastorza G, Egurbide MV et al (2007) Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus. Lupus 16:810–816

  51. 51.

    Espinosa G, Bucciarelli S, Tàssies D et al (2007) Persistently positive antiphospholipid antibodies are related with the appearance of thrombosis during follow-up of patients with antiphospholipid syndrome (abstract). Arthritis Rheum 56:s554

  52. 52.

    Cervera R, Khamashta MA, Shoenfeld Y et al (2009) Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicenter prospective study of 1,000 patients. Ann Rheum Dis 68:1428–1432

  53. 53.

    Sorice M, Griggi T, Circella A et al (1994) Detection of antiphospholipid antibodies by immunostaining on thin layer chromatography plates. J Immunol Methods 173:49–54

  54. 54.

    Erkan D, Derksen WJ, Kaplan V et al (2005) Real world experience with antiphospholipid antibody tests: how stable are results over time? Ann Rheum Dis 64:1321–1325

  55. 55.

    Rodríguez-Fernández S, Saavedra Ramírez P, Espinosa Garriga G et al (2009) Suspensión de la anticoagulación en pacientes con síndrome antifosfolipídico primario en los que se negativizan los anticuerpos antifosfolipídicos. Rev Clin Esp 209:357–358

  56. 56.

    Silver RK, MacGregor SN, Sholl JS et al (1993) Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. Am J Obstet Gynecol 169:1411–1417

  57. 57.

    Balasch J, Carmona F, Lopez-Soto A et al (1993) Low-dose aspirin for prevention of pregnancy losses in women with primary antiphospholipid syndrome. Hum Reprod 8:2234–2239

  58. 58.

    Carmona F, Font J, Azulay M et al (2001) Risk factors associated with fetal losses in treated antiphospholipid syndrome pregnancies: a multivariate analysis. Am J Reprod Immunol 46:274–279

  59. 59.

    Lima F, Khamashta MA, Buchanan NM et al (1996) A study of sixty pregnancies in patients with the antiphospholipid syndrome. Clin Exp Rheumatol 14:131–136

  60. 60.

    Granger KA, Farquharson RG (1997) Obstetric outcome in antiphospholipid syndrome. Lupus 6:509–513

  61. 61.

    Huong DL, Wechsler B, Bletry O et al (2001) A study of 75 pregnancies in patients with antiphospholipid syndrome. J Rheumatol 28:2025–2030

  62. 62.

    Silveira LH, Hubble CL, Jara LJ et al (1992) Prevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin. Am J Med 93:403–411

  63. 63.

    Ruiz-Irastorza G, Khamashta MA, Hughes GR (2001) Antiaggregant and anticoagulant therapy in systemic lupus erythematosus and Hughes’ syndrome. Lupus 10:241–245

  64. 64.

    Rosove MH, Tabsh K, Wasserstrum N et al (1990) Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. Obstet Gynecol 75:630–634

  65. 65.

    Bates SM, Greer IA, Pabinger I et al (2008) Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133:844S–886S

  66. 66.

    Kutteh WH, Rote NS, Silver R (1999) Antiphospholipid antibodies and reproduction: the antiphospholipid antibody syndrome. Am J Reprod Immunol 41:133–152

  67. 67.

    ACOG Committee on Practice Bulletins-Obstetrics (2005) ACOG Practice Bulletin #68: Antiphospholipid syndrome. Obstet Gynecol 106:1113–1121

  68. 68.

    Derksen RH, De Groot PG, Nieuwenhuis HK et al (2001) How to treat women with antiphospholipid antibodies in pregnancy? Ann Rheum Dis 60:1–3

  69. 69.

    Myones BL, McCurdy D (2000) The antiphospholipid syndrome: immunologic and clinical aspects. Clinical spectrum and treatment. J Rheumatol 58 (Suppl):20–28

  70. 70.

    Empson MB, Lassere M, Craig JC et al (2005) Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database of Systematic Reviews, Issue 2. Art. no. CD002859

  71. 71.

    Rai R, Cohen H, Dave M et al (1997) Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 314:253–257

  72. 72.

    Kutteh WH (1996) Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol 174:1584–1589

  73. 73.

    Farquharson RG, Quenby S, Greaves M (2002) Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 100:408–413

  74. 74.

    Balasch J, Font J, Lopez-Soto A et al (1990) Antiphospholipid antibodies in unselected patients with repeated abortion. Hum Reprod 5:43–46

  75. 75.

    Pattison NS, Chamley LW, Birdsall M et al (2000) Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. Am J Obstet Gynecol 183:1008–1012

  76. 76.

    Cowchock S, Reece EA (1997) Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial. Am J Obstet Gynecol 176:1099–1100

  77. 77.

    Asherson RA, Cervera R, Piette JC et al (1998) Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore) 77:195–207

  78. 78.

    Asherson RA, Cervera R, Piette JC et al (2001) Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 80:355–377

  79. 79.

    Bayraktar UD, Erkan D, Bucciarelli S et al (2007) The clinical spectrum of catastrophic antiphospholipid syndrome in the absence and presence of lupus. J Rheumatol 34:346–352

  80. 80.

    Asherson RA, Cervera R, de Groot PG et al (2003) Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 12:530–534

Download references

Author information

Correspondence to Ricard Cervera.

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • Antiphospholipid syndrome
  • Antiphospholipid antibodies
  • Therapy