https://doi.org/10.4081/itjm.2023.1649
A review on management of antiphospholipid syndrome in clinical practice
Published: 13 September 2023
Abstract Views: 1527
PDF: 645
HTML: 25
HTML: 25
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in patients with persistent antiphospholipid antibodies. Thrombotic APS is characterized by venous, arterial, or microvascular thrombosis. The diagnosis is accepted when both one clinical and one laboratory criteria according to the updated Sapporo classification are established. APS may occur in combination with other autoimmune diseases, mainly systemic lupus erythematosus, or in its primary form. Long-term anticoagulation with a vitamin K antagonist is the standard of care for patients who develop thrombosis, considering the high rate of recurrent thrombosis. The current international guidelines are not in favor of recommending direct oral anticoagulants for secondary prevention of thrombotic antiphospholipid syndrome, especially in the context of arterial thrombosis and triple-positive antiphospholipid patients. The most common approach, endorsed by the American College of Chest Physicians guidelines is the combination of heparin and low-dose aspirin (75-100 mg) daily for women who fulfill the clinical and serologic criteria for obstetric APS. New potential therapeutic approaches are under evaluation but actually the anticoagulation remains the cornerstone of treatment.
Miyakis S, Lockshin MD, 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: https://doi.org/10.1111/j.1538-7836.2006.01753.x
Cervera R, Piette JC, 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;46:1019-27.
DOI: https://doi.org/10.1002/art.10187
Cervera R, Espinosa G. Update on the catastrophic antiphospholipid syndrome and the “CAPS Registry”. Semin Thromb Hemost 2012;38:333-8.
DOI: https://doi.org/10.1055/s-0032-1304718
Asherson RA, Cervera R, de Groot PG, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 2003;12:530-4.
DOI: https://doi.org/10.1191/0961203303lu394oa
Rodriguez-Pinto I, Moitinho M, Santacreu I, et al. Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of 500 patients from the international CAPS registry. Autoimmun Rev 2016.
DOI: https://doi.org/10.1016/j.autrev.2016.09.010
Asherson RA. The catastrophic antiphospholipid syndrome, 1998. A review of the clinical features, possible pathogenesis and treatment. Lupus 1998;7:S55-62.
DOI: https://doi.org/10.1177/096120339800700214
Cervera R, Serrano R, Pons-Estel GJ, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2015;74:1011-8.
DOI: https://doi.org/10.1136/annrheumdis-2013-204838
Cohen H, Cuadrado MJ, Erkan D, et al. (16th International Congress on Antiphospholipid Antibodies Task Force report on antiphospholipid syndrome treatments trends. Lupus 2020;29:1571-93.
DOI: https://doi.org/10.1177/0961203320950461
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;42:1309-11.
DOI: https://doi.org/10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F
Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the subcommittee on lupus anticoagulant/ antiphospholipid antibody of the scientific and standardization committee of the ISTH. Thromb Haemost 1995;74:1185-90.
DOI: https://doi.org/10.1055/s-0038-1649901
Pengo V, Tripodi A, Reber G, et al. Update of the guidelines for lupus anticoagulant detection. Subcommittee on lupus anticoagulant/antiphospholipid antibody of the Scientific and Standardisation committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2009;7:1737-40.
DOI: https://doi.org/10.1111/j.1538-7836.2009.03555.x
Knight JS, Branch DW, Ortel TL. Antiphospholipid syndrome: advances in diagnosis, pathogenesis, and management. BMJ 2023;380:e069717.
DOI: https://doi.org/10.1136/bmj-2021-069717
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;104:332-8.
DOI: https://doi.org/10.1016/S0002-9343(98)00060-6
Garcia D, Akl EA, Carr R, Kearon C. Antiphospholipid antibodies and the risk of recurrence after a first episode of venous thromboembolism: a systematic review. Blood 2013;122:817-24.
DOI: https://doi.org/10.1182/blood-2013-04-496257
Pengo V, Ruffatti A, Legnani C, et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost 2010;8:237-42.
DOI: https://doi.org/10.1111/j.1538-7836.2009.03674.x
Gebhart J, Posch F, Koder S, et al. Increased mortality in patients with the lupus anticoagulant: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS). Blood 2015;125:3477-83.
DOI: https://doi.org/10.1182/blood-2014-11-611129
Moll S, Ortel TL. Monitoring warfarin therapy in patients with lupus anticoagulants. Ann Intern Med 1997;127:177-85.
DOI: https://doi.org/10.7326/0003-4819-127-3-199708010-00001
Rosborough TK, Shepherd MF. Unreliability of international normalized ratio for monitoring warfarin therapy in patients with lupus anticoagulant. Pharmacotherapy 2004;24:838-42.
DOI: https://doi.org/10.1592/phco.24.9.838.36102
Arnaud L, Mathian A, Ruffatti A, et al. Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative meta-analysis. Autoimmun Rev 2014;13:281-91.
DOI: https://doi.org/10.1016/j.autrev.2013.10.014
Tektonidou MG, Andreoli L, Limper M, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 2019;78:1296-304.
DOI: https://doi.org/10.1136/annrheumdis-2019-215213
Tarr T, Lakos G, Bhattoa HP, et al. Analysis of risk factors for the development of thrombotic complications in antiphospholipid antibody positive lupus patients. Lupus 2007;16:39-45.
DOI: https://doi.org/10.1177/0961203306074767
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;61:29-36.
DOI: https://doi.org/10.1002/art.24232
Drosos GC, Vedder D, Houben E, et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal disease, including systemic lupus erythematosus and antiphospholipid syndrome. ANN Rheum Dis 2022;81:768-79.
DOI: https://doi.org/10.1136/annrheumdis-2021-221733
Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009;360:1851-61.
DOI: https://doi.org/10.1056/NEJMoa0900241
Delluc A, Ghanima W, Kovacs MJ, et al. Statins for venous event reduction in patients with venous thromboembolism: A multicenter randomized controlled pilot trial assessing feasibility. J Thromb Haemost 2022;20:126-32.
DOI: https://doi.org/10.1111/jth.15537
Kunutsor SK, Seidu S, Khunti K. Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies. Eur Heart J 2017;38:1608-12.
DOI: https://doi.org/10.1093/eurheartj/ehx107
Yoshikawa Y, Yamashita Y, Morimoto T, et al. Effect of statins on recurrent venous thromboembolism (from the COMMAND VTE Registry). Am J Cardiol 2020;125:189-97.
DOI: https://doi.org/10.1016/j.amjcard.2019.10.011
Li R, Yuan M, Yu S, et al. Effect of statins on the risk of recurrent venous thromboembolism: A systematic review and meta-analysis. Pharmacol Res 2021;165:105413.
DOI: https://doi.org/10.1016/j.phrs.2020.105413
Zhu H, Zheng H, Xu T, et al. Effects of statins in primary and secondary prevention for venous thromboembolism events: A meta-analysis. Vascul Pharmacol 2022;142:106931.
DOI: https://doi.org/10.1016/j.vph.2021.106931
Joseph P, Glynn R, Ramasundarahettige C, et al. Rosuvastatin for the prevention of venous thromboembolism: A pooled analysis of the HOPE-3 and JUPITER randomized controlled trials. Cardiovasc Res 2022;118:897-903.
DOI: https://doi.org/10.1093/cvr/cvab078
Siniscalchi C, Quintavalla R, Rocci A, et al. Statin and all-cause mortality in patients receiving anticoagulant therapy for venous thromboembolism. Data from the RIETE registry. Eur J Intern Med 2019;68:30-5.
DOI: https://doi.org/10.1016/j.ejim.2019.07.028
Siniscalchi C, Suriñach JM, Visonà A, et al. Different types of statins and all-cause mortality in patients receiving anticoagulant therapy for venous thromboembolism. Validation study from the RIETE registry. TH Open 2020;4:e236-e244.
DOI: https://doi.org/10.1055/s-0040-1716734
Siniscalchi C, Muriel A, Suriñach Caralt JM, et al. Statin use and 30-day mortality in patients with acute symptomatic pulmonary embolism. J Thromb Haemost 2022;20:1839-51.
DOI: https://doi.org/10.1111/jth.15753
Siniscalchi C. Protective role of statins during anticoagulation for venous thromboembolism: beyond their lipid lowering effect? Eur J Intern Med 2020;79:127-9.
DOI: https://doi.org/10.1016/j.ejim.2020.04.026
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;349:1133-8.
DOI: https://doi.org/10.1056/NEJM200312253492627
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;3:848-53.
DOI: https://doi.org/10.1111/j.1538-7836.2005.01340.x
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;20:206-18.
DOI: https://doi.org/10.1177/0961203310395803
Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTe disease: chest guideline and expert panel report. Chest 2016;149:315-52.
DOI: https://doi.org/10.1016/j.chest.2015.11.026
Levine SR, Brey RL, Tilley BC, et al. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 2004;291:576-84.
DOI: https://doi.org/10.1001/jama.291.5.576
Okuma H, Kitagawa Y, Yasuda T, et al. Comparison between single antiplatelet therapy and combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome. Int J Med Sci 2009;7:15-8.
DOI: https://doi.org/10.7150/ijms.7.15
Son M, Wypasek E, Celinska-Lowenhoff M, Undas A. The use of rivaroxaban in patients with antiphospholipid syndrome: a series of 12 cases. Thromb Res 2015;135:1035-6.
DOI: https://doi.org/10.1016/j.thromres.2015.01.028
Schaefer JK, McBane RD, Black DF, et al. Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients. Thromb Haemost 2014;112:947-50.
DOI: https://doi.org/10.1160/th14-03-0272
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.
DOI: https://doi.org/10.1002/ajh.23797
Haladyj E, Olesinska M. Rivaroxaban - a safe therapeutic option in patients with antiphospholipid syndrome? Our experience in 23 cases. Reumatologia 2016;54:146-9.
DOI: https://doi.org/10.5114/reum.2016.61217
Betancur JF, Bonilla-Abadia F, Hormaza AA, et al. Direct oral anticoagulants in antiphospholipid syndrome: a real life case series. Lupus 2016;25:658-62.
DOI: https://doi.org/10.1177/0961203315624555
Noel N, Dutasta F, Costedoat-Chalumeau N, et al. Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in antiphospholipid syndrome. Autoimmun Rev 2015;14:680-5.
DOI: https://doi.org/10.1016/j.autrev.2015.03.007
Sciascia S, Breen K, Hunt BJ. Rivaroxaban use in patients with antiphospholipid syndrome and previous venous thromboembolism. Blood Coagul Fibrinolysis 2015;26:476-7.
DOI: https://doi.org/10.1097/MBC.0000000000000247
Arachchillage DRJ, Gomez K, Alikhan R, et al. Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012;157:47-58): use of direct acting oral anticoagulants. Br J Haematol 2020;189:212-5.
DOI: https://doi.org/10.1111/bjh.16308
Espinosa G, Cervera R. Current treatment of antiphospholipid syndrome: lights and shadows. Nat Rev Rheumatol 2015;11:586-96.
DOI: https://doi.org/10.1038/nrrheum.2015.88
Chaturvedi S, McCrae KR. Diagnosis and management of the antiphospholipid syndrome. Blood Rev 2017;31:406-17.
DOI: https://doi.org/10.1016/j.blre.2017.07.006
Zikos TA, Sokolove J, Ahuja N, Berube C. Eculizumab induces sustained remission in a patient with refractory primary catastrophic Antiphospholipid syndrome. J Clin Rheumatol 2015;21:311-3.
DOI: https://doi.org/10.1097/RHU.0000000000000290
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;64:2719-23.
DOI: https://doi.org/10.1002/art.34440
Lonze BE, Zachary AA, Magro CM, et al. Eculizumab prevents recurrent antiphospholipid antibody syndrome and enables successful renal transplantation. Am J Transplant 2014;14:459-65.
DOI: https://doi.org/10.1111/ajt.12540
Wig S, Chan M, Thachil J, et al. A case of relapsing and refractory catastrophic antiphospholipid syndrome successfully managed with eculizumab, a complement 5 inhibitor. Rheumatology (Oxford) 2016;55:382-4.
DOI: https://doi.org/10.1093/rheumatology/kev371
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.
DOI: https://doi.org/10.1097/MD.0000000000000143
Yun Z, Duan L, Liu X, et al. An update on the biologics for the treatment of antiphospholipd syndrome. Front Immunol. 2023 May 19;14:1145145. doi: 10.3389/fimmu.2023.1145145
DOI: https://doi.org/10.3389/fimmu.2023.1145145
Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice guidelines. Chest 2012;141:e691S-736S.
DOI: https://doi.org/10.1378/chest.11-2300
Backos M, Rai R, Baxter N, et al. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol 1999;106:102-7.
DOI: https://doi.org/10.1111/j.1471-0528.1999.tb08208.x
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). BMJ 1997;314:253-7.
DOI: https://doi.org/10.1136/bmj.314.7076.253
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;174:1584-9.
DOI: https://doi.org/10.1016/S0002-9378(96)70610-5
How to Cite
Siniscalchi, C., Rossetti, P., Carolla, G., Di Micco, P., Stella, A., & Riva, M. (2023). A review on management of antiphospholipid syndrome in clinical practice. Italian Journal of Medicine, 17(2). https://doi.org/10.4081/itjm.2023.1649
Copyright (c) 2023 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
