Management of Recurrent Thrombosis in Antiphospholipid Syndrome

  • Cecilia Nalli
  • Laura Andreoli
  • Cinzia Casu
  • Angela Tincani
ANTIPHOSPHOLIPID SYNDROME (D ERKAN, SECTION EDITOR)
Part of the following topical collections:
  1. Topical Collection on Antiphospholipid Syndrome

Abstract

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.

Keywords

Antiphospholipid antibodies Anticardiolipin antibodies Anti-β2glycoprotein I antibodies Lupus anticoagulant Thrombosis Recurrent thrombosis Stroke Primary antiphospholipid syndrome Cardiovascular risk factors Warfarin Low-dose aspirin Hydroxychloroquine Statins Heparin Rituximab Management 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of major importance

  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    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.Google Scholar
  3. 3.
    Roubey RA, Hoffman M. From antiphospholipid syndrome to antibody-mediated thrombosis. Lancet. 1997;350(9090):1491–3.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.••
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    Thomas RH. Hypercoagulability syndromes. Arch Intern Med. 2001;161(20):2433–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Andreoli L, Tincani A. Beyond the “syndrome”: antiphospholipid antibodies as risk factors. Arthritis Rheum. 2012;64(2):342–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Roubey RA. Risky business: the interpretation, use, and abuse of antiphospholipid antibody tests in clinical practice. Lupus. 2010;19(4):440–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Meroni PL, Borghi MO, Raschi E, Tedesco F. Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol. 2011;7(6):330–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Giannakopoulos B, Krilis SA. The pathogenesis of the antiphospholipid syndrome. N Engl J Med. 2013;368(11):1033–44.PubMedCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.••
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Szekanecz Z, Koch AE. Vascular involvement in rheumatic diseases: ‘vascular rheumatology’. Arthritis Res Ther. 2008;10(5):224.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedGoogle Scholar
  19. 19.
    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.CrossRefGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    Sciascia S, Sanna G, Murru V, Roccatello D, et al. GAPSS: the global anti-phospholipid syndrome score. Rheumatology (Oxford). 2013;52(8):1397–403.CrossRefGoogle Scholar
  22. 22.
    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.PubMedCrossRefGoogle Scholar
  23. 23.
    Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295(9):1050–7. Review.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCentralPubMedGoogle Scholar
  27. 27.
    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.PubMedCrossRefGoogle Scholar
  28. 28.
    Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med. 1992;117(4):303–8.PubMedCrossRefGoogle Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    Shbaklo H, Kahn SR. Long-term prognosis after deep venous thrombosis. Curr Opin Hematol. 2008;15:494–8.Google Scholar
  31. 31.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.•
    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.PubMedCrossRefGoogle Scholar
  33. 33.•
    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.PubMedCrossRefGoogle Scholar
  34. 34.
    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.PubMedCrossRefGoogle Scholar
  35. 35.
    Cohen H, Machin SJ. Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants? Lupus. 2010;19(4):486–91.PubMedCrossRefGoogle Scholar
  36. 36.
    Pierangeli SS, Erkan D. Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet? Lupus. 2010;19(4):475–85.PubMedCrossRefGoogle Scholar
  37. 37.
    Barbhaiya M, Erkan D. Primary thrombosis prophylaxis in antiphospholipid antibody-positive patients: where do we stand? Curr Rheumatol Rep. 2011;13:59–69.10.PubMedCrossRefGoogle Scholar
  38. 38.
    Erkan D, Pierangeli SS. Could statins be a new therapeutic option for antiphospholipid syndrome patients? Expert Rev Hematol. 2013;6(2):115–7.PubMedCrossRefGoogle Scholar
  39. 39.
    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.Google Scholar
  40. 40.
    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.PubMedCrossRefGoogle Scholar
  41. 41.
    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.PubMedCrossRefGoogle Scholar
  42. 42.
    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.PubMedCrossRefGoogle Scholar
  43. 43.
    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.PubMedGoogle Scholar
  44. 44.
    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.PubMedCrossRefGoogle Scholar
  45. 45.
    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.PubMedCrossRefGoogle Scholar
  46. 46.
    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.PubMedCrossRefGoogle Scholar
  47. 47.
    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.PubMedCrossRefGoogle Scholar
  48. 48.
    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.Google Scholar
  49. 49.
    Pengo V, Denas G, Banzato A, Bison E, et al. Secondary prevention in thrombotic antiphospholipid syndrome. Lupus. 2012;21(7):734–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Cecilia Nalli
    • 1
    • 2
    • 3
  • Laura Andreoli
    • 1
    • 3
  • Cinzia Casu
    • 4
    • 5
  • Angela Tincani
    • 1
    • 3
  1. 1.Rheumatology and Clinical Immunology, Department of Clinical and Experimental SciencesSpedali Civili and University of BresciaBresciaItaly
  2. 2.Rheumatology ChairUniversity of PaviaPaviaItaly
  3. 3.BresciaItaly
  4. 4.Rheumatology UnitNiguarda “Ca’ Granda” HospitalMilanItaly
  5. 5.MilanItaly

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