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.
Keywords: Antiphospholipid syndrome, Antiphospholipid antibodies, Therapy
References
- 1.Miyakis S., Lockshin M.D., Atsumi T., et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) J Thromb Haemost. 2006;4:295–306. doi: 10.1111/j.1538-7836.2006.01753.x. [DOI] [PubMed] [Google Scholar]
- 2.Asherson R.A., Khamashta M.A., Ordi-Ros J., et al. The “primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 1989;68:366–374. doi: 10.1097/00005792-198911000-00004. [DOI] [PubMed] [Google Scholar]
- 3.Cervera R. Lessons from the “Euro-Phospholipid” project. Autoimmun Rev. 2008;7:174–178. doi: 10.1016/j.autrev.2007.11.011. [DOI] [PubMed] [Google Scholar]
- 4.Asherson R.A. The catastrophic antiphospholipid syndrome. J Rheumatol. 1992;19:508–512. [PubMed] [Google Scholar]
- 5.Cervera R., Piette J.C., Font J., et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46:1019–1027. doi: 10.1002/art.10187. [DOI] [PubMed] [Google Scholar]
- 6.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;54:2568–2576. doi: 10.1002/art.22018. [DOI] [PubMed] [Google Scholar]
- 7.Shah N.M., Khamashta M.A., Atsumi T., et al. Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients. Lupus. 1998;7:3–6. doi: 10.1191/096120398678919624. [DOI] [PubMed] [Google Scholar]
- 8.Finazzi G., Brancaccio V., Moia M., et al. 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. 1996;100:530–536. doi: 10.1016/S0002-9343(96)00060-5. [DOI] [PubMed] [Google Scholar]
- 9.Girón-González J.A., García del Rio E., Rodríguez C., et al. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol. 2004;31:1560–1567. [PubMed] [Google Scholar]
- 10.Somers E., Magder L.S., Petri M. Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol. 2002;29:2531–2536. [PubMed] [Google Scholar]
- 11.Forastiero R., Martinuzzo M., Pombo G., et al. A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis. J Thromb Haemost. 2005;3:1231–1238. doi: 10.1111/j.1538-7836.2005.01295.x. [DOI] [PubMed] [Google Scholar]
- 12.Erkan D., Harrison M.J., 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;56:2382–2391. doi: 10.1002/art.22663. [DOI] [PubMed] [Google Scholar]
- 13.Gerosa M., Chighizola C., Meroni P.L. Aspirin in asymptomatic patients with confirmed positivity of antiphospholipid antibodies? Yes (in some cases) Intern Emerg Med. 2008;3:201–203. doi: 10.1007/s11739-008-0170-y. [DOI] [PubMed] [Google Scholar]
- 14.Erkan D. Lupus and thrombosis. J Rheumatol. 2006;33:1715–1717. [PubMed] [Google Scholar]
- 15.Wahl D.G., Bounameaux H., de Moerloose P., et al. 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;160:2042–2048. doi: 10.1001/archinte.160.13.2042. [DOI] [PubMed] [Google Scholar]
- 16.Ruiz-Irastorza G., Egurbide M.V., Pijoan J.I., et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus. 2006;15:577–583. doi: 10.1177/0961203306071872. [DOI] [PubMed] [Google Scholar]
- 17.Erkan D., Yazici Y., Peterson M.G., et al. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford) 2002;41:924–929. doi: 10.1093/rheumatology/41.8.924. [DOI] [PubMed] [Google Scholar]
- 18.Erkan D., Merrill J.T., Yazici Y., et al. High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum. 2001;44:1466–1467. doi: 10.1002/1529-0131(200106)44:6<1466::AID-ART242>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
- 19.Tincani A., Taglietti M., Biasini C., et al. Thromboembolic events after fetal loss in patients with antiphospholipid syndrome: comment on the article by Erkan et al. Arthritis Rheum. 2002;46:1126–1127. doi: 10.1002/art.10165. [DOI] [PubMed] [Google Scholar]
- 20.Ruffatti A., Del Ross T., Ciprian M., et al. Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicenter retrospective follow-up study. Ann Rheum Dis. 2009;68:397–399. doi: 10.1136/ard.2008.096669. [DOI] [PubMed] [Google Scholar]
- 21.Wahl D.G., Guillemin F., de Maistre E., et al. Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus -a meta-analysis. Lupus. 1997;6:467–473. doi: 10.1177/096120339700600510. [DOI] [PubMed] [Google Scholar]
- 22.Wahl D.G., Guillemin F., de Maistre E., et al. Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus. 1998;7:15–22. doi: 10.1191/096120398678919688. [DOI] [PubMed] [Google Scholar]
- 23.Galli M., Luciani D., Bertolini G., et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;101:1827–1832. doi: 10.1182/blood-2002-02-0441. [DOI] [PubMed] [Google Scholar]
- 24.Turiel M., Sarzi-Puttini P., Peretti R., et al. Thrombotic risk factors in primary antiphospholipid syndrome: a 5-year prospective study. Stroke. 2005;36:1490–1494. doi: 10.1161/01.STR.0000170645.40562.09. [DOI] [PubMed] [Google Scholar]
- 25.Galli M., Luciani D., Bertolini G., et al. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood. 2003;102:2717–2723. doi: 10.1182/blood-2002-11-3334. [DOI] [PubMed] [Google Scholar]
- 26.Ruiz-Irastorza G., Hunt B.J., Khamashta M.A. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum. 2007;57:1487–1495. doi: 10.1002/art.23109. [DOI] [PubMed] [Google Scholar]
- 27.Lim W., Crowther M.A., Eikelboom J.W. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295:1050–1057. doi: 10.1001/jama.295.9.1050. [DOI] [PubMed] [Google Scholar]
- 28.Rosove M.H., Brewer P.M. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med. 1992;117:303–308. doi: 10.7326/0003-4819-117-4-303. [DOI] [PubMed] [Google Scholar]
- 29.Derksen R.H., de Groot P.G., Kater L., et al. Patients with antiphospholipid antibodies and venous thrombosis should receive long term anticoagulant treatment. Ann Rheum Dis. 1993;52:689–692. doi: 10.1136/ard.52.9.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Khamashta M.A., Cuadrado M.J., Mujic F., et al. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. 1995;332:993–997. doi: 10.1056/NEJM199504133321504. [DOI] [PubMed] [Google Scholar]
- 31.Krnic-Barrie S., O’Connor C.R., Looney S.W., et al. A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis. Arch Intern Med. 1997;157:2101–2108. doi: 10.1001/archinte.1997.00440390101013. [DOI] [PubMed] [Google Scholar]
- 32.Muñoz-Rodríguez F.J., Font J., Cervera R., et al. Clinical study and follow-up of 100 patients with the antiphospholipid syndrome. Semin Arthritis Rheum. 1999;29:182–190. doi: 10.1016/S0049-0172(99)80029-8. [DOI] [PubMed] [Google Scholar]
- 33.Ruiz-Irastorza G., Khamashta M.A., Hunt B.J., 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;162:1164–1169. doi: 10.1001/archinte.162.10.1164. [DOI] [PubMed] [Google Scholar]
- 34.Ames P.R., Ciampa A., Margaglione M., et al. 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. 2005;93:694–699. doi: 10.1160/TH04-11-0723. [DOI] [PubMed] [Google Scholar]
- 35.Wittkowsky A.K., Downing J., Blackburn J., et al. Warfarin-related outcomes in patients with antiphospholipid antibody syndrome managed in an anticoagulation clinic. Thromb Haemost. 2006;96:137–141. [PubMed] [Google Scholar]
- 36.Ginsberg J.S., Wells P.S., Brill-Edwards P., et al. Antiphospholipid antibodies and venous thromboembolism. Blood. 1995;86:3685–3691. [PubMed] [Google Scholar]
- 37.Prandoni P., Simioni P., Girolami A. Antiphospholipid antibodies, recurrent thromboembolism, and intensity of warfarin anticoagulation. Thromb Haemost. 1996;75:859. [PubMed] [Google Scholar]
- 38.Rance A., Emmerich J., Fiessinger J.N. Anticardiolipin antibodies and recurrent thromboembolism. Thromb Haemost. 1997;77:221–222. [PubMed] [Google Scholar]
- 39.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;104:332–338. doi: 10.1016/S0002-9343(98)00060-6. [DOI] [PubMed] [Google Scholar]
- 40.Crowther M.A., Ginsberg J.S., 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;349:1133–1138. doi: 10.1056/NEJMoa035241. [DOI] [PubMed] [Google Scholar]
- 41.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;3:848–853. doi: 10.1111/j.1538-7836.2005.01340.x. [DOI] [PubMed] [Google Scholar]
- 42.Ho W.K., Hankey G.J., Quinlan D.J., et al. Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med. 2006;166:729–736. doi: 10.1001/archinte.166.7.729. [DOI] [PubMed] [Google Scholar]
- 43.Hron G., Eichinger S., Weltermann A., et al. Family history for venous thromboembolism and the risk for recurrence. Am J Med. 2006;119:50–53. doi: 10.1016/j.amjmed.2005.04.043. [DOI] [PubMed] [Google Scholar]
- 44.Auerbach A.D., Sanders G.D., Hambleton J. Cost-effectiveness of testing for hypercoagulability and effects on treatment strategies in patients with deep vein thrombosis. Am J Med. 2004;116:816–828. doi: 10.1016/j.amjmed.2004.01.017. [DOI] [PubMed] [Google Scholar]
- 45.Straczek C., Alhenc-Gelas M., Aubry M.L., et al. Genetic variation at the estrogen receptor alpha locus in relation to venous thromboembolism risk among postmenopausal women. J Thromb Haemost. 2005;3:1535–1537. doi: 10.1111/j.1538-7836.2005.01450.x. [DOI] [PubMed] [Google Scholar]
- 46.Straczek C., Oger E., Yon de Jonage-Canonico M.B., et al. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation. 2005;112:3495–3500. doi: 10.1161/CIRCULATIONAHA.105.565556. [DOI] [PubMed] [Google Scholar]
- 47.Chopra N., Koren S., Greer W.L., et al. Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with antiphospholipid antibodies. J Rheumatol. 2002;29:1683–1688. [PubMed] [Google Scholar]
- 48.Galli M., Finazzi G., Duca F., et al. 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. 2000;108:865–870. doi: 10.1046/j.1365-2141.2000.01964.x. [DOI] [PubMed] [Google Scholar]
- 49.Galli M., Borrelli G., Jacobsen E.M., et al. Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood. 2007;110:1178–1183. doi: 10.1182/blood-2007-01-066043. [DOI] [PubMed] [Google Scholar]
- 50.Martínez-Berriotxoa A., Ruiz-Irastorza G., Egurbide M.V., et al. Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus. Lupus. 2007;16:810–816. doi: 10.1177/0961203307083316. [DOI] [PubMed] [Google Scholar]
- 51.Espinosa G., Bucciarelli S., Tàssies D., et al. Persistently positive antiphospholipid antibodies are related with the appearance of thrombosis during follow-up of patients with antiphospholipid syndrome (abstract) Arthritis Rheum. 2007;56:s554. [Google Scholar]
- 52.Cervera R., Khamashta M.A., Shoenfeld Y., et al. Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicenter prospective study of 1,000 patients. Ann Rheum Dis. 2009;68:1428–1432. doi: 10.1136/ard.2008.093179. [DOI] [PubMed] [Google Scholar]
- 53.Sorice M., Griggi T., Circella A., et al. Detection of antiphospholipid antibodies by immunostaining on thin layer chromatography plates. J Immunol Methods. 1994;173:49–54. doi: 10.1016/0022-1759(94)90282-8. [DOI] [PubMed] [Google Scholar]
- 54.Erkan D., Derksen W.J., Kaplan V., et al. Real world experience with antiphospholipid antibody tests: how stable are results over time? Ann Rheum Dis. 2005;64:1321–1325. doi: 10.1136/ard.2004.031856. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Rodríguez-Fernández S., Saavedra Ramírez P., Espinosa Garriga G., et al. Suspensión de la anticoagulación en pacientes con síndrome antifosfolipídico primario en los que se negativizan los anticuerpos antifosfolipídicos. Rev Clin Esp. 2009;209:357–358. doi: 10.1016/S0014-2565(09)71823-5. [DOI] [PubMed] [Google Scholar]
- 56.Silver R.K., MacGregor S.N., Sholl J.S., et al. Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. Am J Obstet Gynecol. 1993;169:1411–1417. doi: 10.1016/0002-9378(93)90410-K. [DOI] [PubMed] [Google Scholar]
- 57.Balasch J., Carmona F., Lopez-Soto A., et al. Low-dose aspirin for prevention of pregnancy losses in women with primary antiphospholipid syndrome. Hum Reprod. 1993;8:2234–2239. doi: 10.1093/oxfordjournals.humrep.a138009. [DOI] [PubMed] [Google Scholar]
- 58.Carmona F., Font J., Azulay M., et al. Risk factors associated with fetal losses in treated antiphospholipid syndrome pregnancies: a multivariate analysis. Am J Reprod Immunol. 2001;46:274–279. doi: 10.1034/j.1600-0897.2001.d01-13.x. [DOI] [PubMed] [Google Scholar]
- 59.Lima F., Khamashta M.A., Buchanan N.M., et al. A study of sixty pregnancies in patients with the antiphospholipid syndrome. Clin Exp Rheumatol. 1996;14:131–136. [PubMed] [Google Scholar]
- 60.Granger K.A., Farquharson R.G. Obstetric outcome in antiphospholipid syndrome. Lupus. 1997;6:509–513. doi: 10.1177/096120339700600606. [DOI] [PubMed] [Google Scholar]
- 61.Huong D.L., Wechsler B., Bletry O., et al. A study of 75 pregnancies in patients with antiphospholipid syndrome. J Rheumatol. 2001;28:2025–2030. [PubMed] [Google Scholar]
- 62.Silveira L.H., Hubble C.L., Jara L.J., et al. Prevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin. Am J Med. 1992;93:403–411. doi: 10.1016/0002-9343(92)90170-G. [DOI] [PubMed] [Google Scholar]
- 63.Ruiz-Irastorza G., Khamashta M.A., Hughes G.R. Antiaggregant and anticoagulant therapy in systemic lupus erythematosus and Hughes’ syndrome. Lupus. 2001;10:241–245. doi: 10.1191/096120301667789546. [DOI] [PubMed] [Google Scholar]
- 64.Rosove M.H., Tabsh K., Wasserstrum N., et al. Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. Obstet Gynecol. 1990;75:630–634. [PubMed] [Google Scholar]
- 65.Bates S.M., Greer I.A., Pabinger I., et al. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2008;133:844S–886S. doi: 10.1378/chest.08-0761. [DOI] [PubMed] [Google Scholar]
- 66.Kutteh W.H., Rote N.S., Silver R. Antiphospholipid antibodies and reproduction: the antiphospholipid antibody syndrome. Am J Reprod Immunol. 1999;41:133–152. doi: 10.1111/j.1600-0897.1999.tb00087.x. [DOI] [PubMed] [Google Scholar]
- 67.ACOG Committee on Practice Bulletins-Obstetrics ACOG Practice Bulletin #68: Antiphospholipid syndrome. Obstet Gynecol. 2005;106:1113–1121. doi: 10.1097/00006250-200511000-00056. [DOI] [PubMed] [Google Scholar]
- 68.Derksen R.H., De Groot P.G., Nieuwenhuis H.K., et al. How to treat women with antiphospholipid antibodies in pregnancy? Ann Rheum Dis. 2001;60:1–3. doi: 10.1136/ard.60.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 69.Myones B.L., McCurdy D. The antiphospholipid syndrome: immunologic and clinical aspects. Clinical spectrum and treatment. J Rheumatol. 2000;58(Suppl):20–28. [PubMed] [Google Scholar]
- 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 [DOI] [PMC free article] [PubMed]
- 71.Rai R., Cohen H., Dave M., et al. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies) BMJ. 1997;314:253–257. doi: 10.1136/bmj.314.7076.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 72.Kutteh W.H. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol. 1996;174:1584–1589. doi: 10.1016/S0002-9378(96)70610-5. [DOI] [PubMed] [Google Scholar]
- 73.Farquharson R.G., Quenby S., Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol. 2002;100:408–413. doi: 10.1016/S0029-7844(02)02165-8. [DOI] [PubMed] [Google Scholar]
- 74.Balasch J., Font J., Lopez-Soto A., et al. Antiphospholipid antibodies in unselected patients with repeated abortion. Hum Reprod. 1990;5:43–46. doi: 10.1093/oxfordjournals.humrep.a137038. [DOI] [PubMed] [Google Scholar]
- 75.Pattison N.S., Chamley L.W., Birdsall M., et al. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. Am J Obstet Gynecol. 2000;183:1008–1012. doi: 10.1067/mob.2000.106754. [DOI] [PubMed] [Google Scholar]
- 76.Cowchock S., Reece E.A. Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial. Am J Obstet Gynecol. 1997;176:1099–1100. doi: 10.1016/S0002-9378(97)70409-5. [DOI] [PubMed] [Google Scholar]
- 77.Asherson R.A., Cervera R., Piette J.C., et al. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore) 1998;77:195–207. doi: 10.1097/00005792-199805000-00005. [DOI] [PubMed] [Google Scholar]
- 78.Asherson R.A., Cervera R., Piette J.C., et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 2001;80:355–377. doi: 10.1097/00005792-200111000-00002. [DOI] [PubMed] [Google Scholar]
- 79.Bayraktar U.D., Erkan D., Bucciarelli S., et al. The clinical spectrum of catastrophic antiphospholipid syndrome in the absence and presence of lupus. J Rheumatol. 2007;34:346–352. [PubMed] [Google Scholar]
- 80.Asherson R.A., Cervera R., de Groot P.G., et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003;12:530–534. doi: 10.1191/0961203303lu394oa. [DOI] [PubMed] [Google Scholar]
