Management of Recurrent Thrombosis in Antiphospholipid Syndrome Authors
ANTIPHOSPHOLIPID SYNDROME (D ERKAN, SECTION EDITOR)
First Online: 22 January 2014 DOI:
Cite this article as: Nalli, C., Andreoli, L., Casu, C. et al. Curr Rheumatol Rep (2014) 16: 405. doi:10.1007/s11926-013-0405-4
One of the challenges of managing patients with antiphospholipid syndrome is the prevention of rethrombosis (secondary prophylaxis). Risk stratification, i.e. traditional cardiovascular and thrombosis risk factors, systemic autoimmune diseases, antiphospholipid antibody profile, and the intensity of anticoagulation are all relevant to the management of APS patients with recurrent thrombosis. The paper will review “state of the art” strategies for optimizing therapy for APS patients with recurrent thrombosis.
Anti-β2glycoprotein I antibodies
Primary antiphospholipid syndrome
Cardiovascular risk factors
This article is part of the Topical Collection on
References Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of major importance
Miyakis S, Lockshin MD, Atsumi T, Branch DW, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.
Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, on behalf of APS ACTION, et al. The estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis. Arthritis Care Res (Hoboken). 2013 Jul 16.
Roubey RA, Hoffman M. From antiphospholipid syndrome to antibody-mediated thrombosis. Lancet. 1997;350(9090):1491–3.
Roldan V, Lecumberri R, Muñoz-Torrero JF, Vicente V, et al. Thrombophilia testing in patients with venous thromboembolism. Findings from the RIETE registry. Thromb Res. 2009;124(2):174–7.
Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, Brey R, 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(2):206–18.
The most up-to-date systematic review on the secondary prevention of thrombosis among APS patients, with recommendations elaborated by an international panel of experts
Thomas RH. Hypercoagulability syndromes. Arch Intern Med. 2001;161(20):2433–9.
Andreoli L, Tincani A. Beyond the “syndrome”: antiphospholipid antibodies as risk factors. Arthritis Rheum. 2012;64(2):342–5.
Roubey RA. Risky business: the interpretation, use, and abuse of antiphospholipid antibody tests in clinical practice. Lupus. 2010;19(4):440–5.
Meroni PL, Borghi MO, Raschi E, Tedesco F. Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol. 2011;7(6):330–9.
Giannakopoulos B, Krilis SA. The pathogenesis of the antiphospholipid syndrome. N Engl J Med. 2013;368(11):1033–44.
Meroni PL, Raschi E, Grossi C, Pregnolato F, et al. Obstetric and vascular APS: same autoantibodies but different diseases? Lupus. 2012;21(7):708–10.
Erkan D, Derksen R, Levy R, Machin S, et al. Antiphospholipid syndrome clinical research task force report. Lupus. 2011;20(2):219–24.
The international consensus report on the definition of a high-risk aPL profile
Urbanus RT, Siegerink B, Roest M, Rosendaal FR, et al. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case–control study. Lancet Neurol. 2009;8(11):998–1005.
Szekanecz Z, Koch AE. Vascular involvement in rheumatic diseases: ‘vascular rheumatology’. Arthritis Res Ther. 2008;10(5):224.
PubMedCentral PubMed CrossRef
Pengo V, Banzato A, Denas G, Jose SP, et al. Correct laboratory approach to APS diagnosis and monitoring. Autoimmun Rev. 2013;12(8):832–4.
Pengo V, Ruffatti A, Legnani C, Testa S, et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood. 2011;118(17):4714–8.
Pengo V, Ruffatti A, Legnani C, Gresele P, et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010;8(2):237–42.
Hernández-Molina G, Espericueta-Arriola G, Cabral AR. The role of lupus anticoagulant and triple marker positivity as risk factors for rethrombosis in patients with primary antiphospholipid syndrome. Clin Exp Rheumatol. 2013;31(3):382–8.
Ruffatti A, Tonello M, Visentin MS, Bontadi A, et al. Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case–control study. Rheumatology (Oxford). 2011;50(9):1684–9.
Otomo K, Atsumi T, Amengual O, Fujieda Y, et al. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum. 2012;64(2):504–12.
Sciascia S, Sanna G, Murru V, Roccatello D, et al. GAPSS: the global anti-phospholipid syndrome score. Rheumatology (Oxford). 2013;52(8):1397–403.
Ruiz-Irastorza G, Hunt BJ, Khamashta MA. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum. 2007;57(8):1487–95.
Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295(9):1050–7. Review.
Crowther MA, Ginsberg JS, Julian J, Denburg 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(12):1133–8.
Finazzi G, Marchioli R, Brancaccio V, Schinco P, 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(5):848–53.
Okuma H, Kitagawa Y, Yasuda T, Tokuoka K, 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(1):15–8.
Cervera R, Khamashta MA, Shoenfeld Y, Camps MT, 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(9):1428–32.
Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med. 1992;117(4):303–8.
Tick LW, Kramer MH, Rosendaal FR, Faber WR, Doggen CJ. Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis. J Thromb Haemost. 2008;6:2075–81.
Shbaklo H, Kahn SR. Long-term prognosis after deep venous thrombosis. Curr Opin Hematol. 2008;15:494–8.
Vazquez SR, Freeman A, VanWoerkom RC, Rondina MT. Contemporary issues in the prevention and management of postthrombotic syndrome. Ann Pharmacother. 2009;43(11):1824–35.
PubMedCentral PubMed CrossRef
Punnialingam S, Khamashta MA. Duration of anticoagulation treatment for thrombosis in APS: is it ever safe to stop? Curr Rheumatol Rep. 2013;15(4):318.
This paper provides an overview of the challenge of recurrent thrombosis in APS and investigates the evidence for alternative management to anticoagulation
Pengo V, Ruiz-Irastorza G, Denas G, Andreoli L, et al. High intensity anticoagulation in the prevention of the recurrence of arterial thrombosis in antiphospholipid syndrome: ‘PROS’ and ‘CONS’. Autoimmun Rev. 2012;11(8):577–80.
In this recent review of the literature, controversial aspects of the management of arterial thrombosis are discussed, with the main focus on the intensity of anticoagulation
Vargas-Hitos JA, Ateka-Barrutia O, Sangle S, Khamashta MA. Efficacy and safety of long-term low molecular weight heparin in patients with antiphospholipid syndrome. Ann Rheum Dis. 2011;70(9):1652–4.
Cohen H, Machin SJ. Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants? Lupus. 2010;19(4):486–91.
Pierangeli SS, Erkan D. Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet? Lupus. 2010;19(4):475–85.
Barbhaiya M, Erkan D. Primary thrombosis prophylaxis in antiphospholipid antibody-positive patients: where do we stand? Curr Rheumatol Rep. 2011;13:59–69.10.
Erkan D, Pierangeli SS. Could statins be a new therapeutic option for antiphospholipid syndrome patients? Expert Rev Hematol. 2013;6(2):115–7.
Erkan D, Willis R, Murthy VL, Basra G, et al. A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients. Ann Rheum Dis. 2013 Aug 9.
Erre GL, Pardini S, Faedda R, Passiu G. Effect of rituximab on clinical and laboratory features of antiphospholipid syndrome: a case report and a review of literature. Lupus. 2008;17(1):50–5.
Berman H, Rodríguez-Pintó I, Cervera R, Morel N, et al. Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab. Autoimmun Rev. 2013;12(11):1085–90.
Erkan D, Vega J, Ramón G, Kozora E, et al. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum. 2013;65(2):464–71.
Sciascia S, Giachino O, Roccatello D. Prevention of thrombosis relapse in antiphospholipid syndrome patients refractory to conventional therapy using intravenous immunoglobulin. Clin Exp Rheumatol. 2012;30(3):409–13.
Martinez-Berriotxoa A, Ruiz-Irastorza G, Egurbide MV, Garmendia M, et al. Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus. Lupus. 2007;16(10):810–6.
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(1):29–36.
Criado-García J, Fernández-Puebla RA, Jiménez LL, Velasco F, et al. Anticoagulation treatment withdrawal in primary antiphospholipid syndrome when anticardiolipin antibodies become negative. [Article in Spanish]. Rev Clin Esp. 2008;208(3):135–7.
Coloma Bazán E, Donate López C, Moreno Lozano P, Cervera R, et al. Discontinuation of anticoagulation or antiaggregation treatment may be safe in patients with primary antiphospholipid syndrome when antiphospholipid antibodies became persistently negative. Immunol Res. 2013;56(2–3):358–61.
Chock YP, Erkan D. Discontinuation of anticoagulation in antiphospholipid syndrome patients with vascular events. Abstract presented at 14th Antiphospholid Antibodies International Congress, September 2013, Rio De Janeiro, Brazil.
Pengo V, Denas G, Banzato A, Bison E, et al. Secondary prevention in thrombotic antiphospholipid syndrome. Lupus. 2012;21(7):734–5.
PubMed CrossRef Copyright information
© Springer Science+Business Media New York 2013