Abstract
The gold standard for treatment of the antiphospholipid antibody syndrome (APS) after thrombosis remains highintensity warfarin, and, in pregnancy, heparin and aspirin. Exciting developments include the potential role of hydroxychloroquine as a prophylactic drug, stem cell transplantation, and B-cell tolerance. Animal models appear to be a fruitful “proving ground” of new therapies. The introduction of revised classification criteria for APS should aid in appropriate characterization of, and selection of, patients for clinical trials.
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References and Recommended Reading
Derksen RHWM, de Groot PG, Kater L, Nieuwenhuis HK: Patients with antiphospholipid antibodies and venous thrombosis should receive long-term anticoagulant treatment. Ann Rheum Dis 1993, 52:689–692.
Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV: the management of thrombosis in the antiphospholipid antibody syndrome. N Engl J Med 1995, 332:993–997. The major case series showing that an INR of 3 is protective against recurrent thromboembolism.
Rosove MH, Brewer PMC: Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992, 117:303–308.
Bern MM, Wallach SR, Bothe Jr. A, et al.: Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann Intern Med 1990, 112(6):423–428.
Levine M, Hirsh J, Gent M, et al.: Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 1994, 343:886–889.
Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk: the Medical Research Council’s General Practice Research Framework. Lancet 1998, 351:233–241.
Krnic-Barrie S, O’Connor CR, Looney SW, et al.: A retrospective review of 61 patients with antiphospholipid syndrome: analysis of factors influencing recurrent thrombosis. Arch Intern Med 1997, 157(18):2101–2108. A retrospective case series that suggests that high-intensity warfarin may not be necessary.
Prandoni P, Simoni P, Girolami A: Antiphospholipid antibodies, recurrent thromboembolism and intensity of oral anticoagulation. Thromb Haemost 1996, 75:859.
Rance A, Emmerich J, Fiessinger J-N: Anticardiolipin antibodies and recurrent thromboembolism. Thromb Haemost 1997, 77:221–222.
Schulman S, Svenungsson E, Granqvist S, the Duration of Anticoagulation Study Group: anticardiolipin antibodies predict early recurrence of thromboembolism and death among patinets with venous thromboembolism following anticoagulant therapy. Am J Med 1998, 104:332–338.
Petri M: Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective. Scand J Rheumatol 1996, 25:191–193.
Cowchock FS, Reece EA, Balaban D, et al.: Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol 1992, 166:1318–1323. The classic clinical trial that found that heparin/aspirin and prednisone/aspirin are equally effective, but heparin/aspirin is associated with fewer side-effects.
Laskin CA, Bombardier C, Hannah ME, et al.: Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N Engl J Med 1997, 337:148–153.
Salafia CM, Parke AL: Placental pathology in systemic lupus erythematosus and phospholipid antibody syndrome. Rheum Dis Clin N Am 1997, 23:85–98.
Rosove MH, Tabsh K, Wasserstrum N, et al.: Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. Obstet Gynecol 1990, 75:630–634.
Kutteh WH: 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. Aspirin alone is beneficial in some women, but overall heparin/ aspirin is superior.
Rai R, Cohen H, Dave M, Regan L: Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). Br Med J 1997, 314(7076):253–257.
Welsch S, Branch DW: Antiphospholipid syndrome in pregnancy. Obstetric concerns and treatment. Rheum Dis Clin North Am 1997, 23:71–84.
Shah NM, Khamashta MA, Atsumi T, Hughes GRV: Outcome of patients with anticardiolipin antibodies: a 10-year follow-up of 52 patients. Lupus 1998, 7:3–6.
Ginsburg KS, Liang MH, Newcomer L, et al.: Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Int Med 1992, 117:997–1002.
Petri M, Lakatta C, Magder L, Goldman DW: Effect of prednisone and hydroxychloroquine on coronary artery disease risk factors in systemic lupus erythematosus: a longitudinal data analysis. Am J Med 1994, 96:254–259. Prednisone increases the total serum cholesterol, mean arterial pressure, and weight. Hydroxychloroquine lowers total serum cholesterol.
Rosing J, Tans G, Nicolaes GA, et al.: Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. Br J Haematol 1997, 97:233–238.
Bloemenkamp KWM, Rosendaal FR, Helmerhorst Fm, et al.: Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995, 346:1593–1596.
Martinelli I, Sacchi E, Landi G, et al.: High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives [comments]. N Engl J Med 1998, 338(25):1793–1797.
Verthelyi D, Ansar Ahmed S: Characterization of estrogeninduced autoantibodies to cardiolipin in nonautoimmune mice. J Autoimmun 1997, 10(2):115–125.
Daly E, Vessey MP, Hawkins MM, et al.: Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 1996, 348:977–980.
Jick H, Jick SS, Myers MW, Vasilakis C: Risk of acute myocardial infarction and low-dose combined oral contraceptives. Lancet 1996, 347:627–628.
Grodstein F, Stampfer MJ, Goldhaber SZ, et al.: Prospective study of exogenous hormones and risk of pulmonary embolism in women. Lancet 1996, 348:983–987.
Hulley S, Grady D, Bush T, et al.: Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women: Heart and Estrogen/ progestin Replacement Study (HERS) research group. JAMA 1998, 280:605–613.
Reverter J-C, Tassies D, Font J, et al.: Effects of human monoclonal anticardiolipin antibodies on platelet function and on tissue factor expression on monocytes. Arthritis Rheum 1998, 41:1420–1427.
Robbins DL, Leung S, Miller-Blair DJ, Ziboh V: Effect of anticardiolipin/ beta-2 glycoprotein I complexes on production of thromboxane A2 by platelets from patients with the antiphospholipid syndrome. J Rheumatol 1998, 25:51–56.
Joseph JE, Donohoe S, Harrison P, et al.: Platelet activation and turnover in the primary antiphospholipid syndrome. Lupus 1998, 7:333–340.
Ford I, Urbaniak S, Greaves M: IgG from patients with antiphospholipid syndrome binds to platelets without induction of platelet activation. Br J Haematol 1998, 102:841–849.
Topol EJ, Byzova TV, Plow EF: Platelet GPIIb-IIIa blockers. Lancet 1999, 353:227–231.
Chesebro JH, Badimon JJ: Platelet glycoprotein IIb/IIIa receptor blockade in unstable coronary disease. N Engl J Med 1998, 338:1539–1540.
Asherson RA, Piette J-C: The catastrophic antiphospholipid syndrome 1996: acute multi-organ failure associated with antiphospholipid antibodies: a review of 31 patients. Lupus 1996, 5:414–417. A retrospective case series in which patients who were plasmapheresed were more likely to survive.
Aringer M, Smolen JS, Graninger WB: Severe infections in plasmapheresis-treated systemic lupus erythematosus. Arthritis Rheum 1998, 41:414–420.
Weisman MH, Bluestein HG, Berner CM, de Haan HA: Reduction in circulating dsDNA antibody titer after administration of LJP 394. J Rheumatol 1997, 24(2):314–318.
Iverson GM, Jones DS, Marquis D, et al.: A chemically defined, toleragen-based approach for targeting anti-b2-glycoprotein I antibodies. Lupus 1998, 7(Suppl. 2):S166-S169. A B-cell toleragen approach to antiphospholipid antibody syndrome.
Musso M, Porretto F, Crescimanno A, et al.: Autologous peripheral blood stem and progenitor (CD34+) cell transplantation for systemic lupus erythematosus complicated by Evans syndrome. Lupus 1998, 7:492–494.
Brodsky RA, Petri M, Smith BD, et al.: Immunoblative highdose cyclophosphamide without stem cell rescue for refractory, severe autoimmune disease. Ann Int Med 1998, 129:1031–1035. High-dose cyclophosphamide—without stem cell transplantation— may be sufficient to lead to long-term remissions in some patients.
Brodsky RA, Sensenbrenner LL, Jones RJ: Complete remission in severe aplastic anemia after high-dose cyclophosphamide without bone marrow transplantation. Blood 1996, 87:491–494.
Harris EN, Pierangeli SS: Utilization of intravenous immunoglobulin therapy to treat recurrent pregnancy loss in the antiphospholipid syndrome: a review. Scand J Rheumatol Suppl 1998, 107:97–102.
Gordon C, Kilby MD: Use of intravenous immunoglobulin therapy in pregnancy in systemic lupus erythematosus and antiphospholipid antibody syndrome. Lupus 1998, 7:429–433.
Birdsall MA, Lockwood GM, Ledger WL, et al.: Antiphospholipid antibodies in women having in-vitro fertilization. Hum Reprod 1996, 11(6):1185–1189.
Sher G, Matzner W, Feinman M, et al.: The selective use of heparin/aspirin therapy, alone or in combination with intravenous immunoglobulin G, in the management of antiphospholipid antibody-positive women undergoing in vitro fertilization. Am J Reprod Immunol 1998, 40:74–82.
Fishman P, Falach-Vaknin E, Sredni B, et al.: Aspirin modulates interleukin-3 production: additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome. J Rheumatol 1995, 22:1086–1090.
Blank M, George J, Fishman P, et al.: Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin-3 and granulocytemacrophage colony-stimulating factor expression. Arthritis Rheum 1998, 41:224–232.
Bakimer R, Guilbrud B, Zurgil N, Shoenfeld Y: The effect of intravenous g-globulin on the induction of experimental antiphospholipid syndrome. Clin Immunol Immunopathol 1993, 69:97–102.
Blank M, Tomer Y, Slavin S, Shoenfeld Y: Induction of tolerance to experimental anti-phospholipid syndrome (APS) by syngeneic bone marrow cell transplantation. Scand J Immunol 1995, 42:226–234.
Piette J-C: 1996 diagnostic and classification criteria for the antiphospholipid/cofactors syndrome: a ‘mission impossible’? Lupus 1996, 5:354–363.
Wilson WA, Gharavi AE, Koike T, et al.: International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999, 42(7):309–311.
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Petri, M. Treatment of the antiphospholipid antibody syndrome: Progress in the last five years?. Curr Rheumatol Rep 2, 256–261 (2000). https://doi.org/10.1007/s11926-000-0088-5
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DOI: https://doi.org/10.1007/s11926-000-0088-5