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The Management of Stroke in Antiphospholipid Syndrome

  • ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)
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Abstract

Ischemic stroke is one of the most common complications of the antiphospholipid syndrome (APS). Because of the relative lack of definitive prospective studies, there is still some debate as to whether the persistent presence of antiphospholipid antibodies (aPLs) increases the risk of recurrent stroke. There is more evidence for aPLs as a risk factor for first stroke. The mechanisms of ischemic stroke are considered to be thrombotic and embolic. APS patients with thrombotic stroke frequently have other, often conventional vascular risk factors. Transesophageal echocardiogram is strongly recommended in APS patients with ischemic stroke because of the high yield of valvular abnormalities. The appropriate management of thrombosis in patients with APS is still controversial because of limited randomized clinical trial data. This review discusses the current evidence for antithrombotic therapy in patients who are aPL positive but do not fulfill criteria for APS, and in APS patients. Alternative and emerging therapies including low molecular weight heparin, new oral anticoagulants (including direct thrombin inhibitors), hydroxychloroquine, statins, and rituximab, are also addressed.

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References

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

  1. Lim W: Antiphospholipid antibody syndrome. Hematology Am Soc Hematol Educ Program. 2009, 233–9.

  2. Rodrigues CE, Carvalho JF, Shoenfeld Y. Neurological manifestations of antiphospholipid syndrome. Eur J Clin Invest. 2010;40:350–9.

    Article  PubMed  Google Scholar 

  3. Janardhan V, Wolf PA, Kase CS, et al. Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack: The Framingham Cohort and Offspring Study. Stroke. 2004;35:736–41.

    Article  PubMed  Google Scholar 

  4. Ahmed E, Stegmayr B, Trifunovic J, et al. Anticardiolipin antibodies are not an independent risk factor for stroke: an incident case-referent study nested within the MONICA and Västerbotten cohort project. Stroke. 2000;31:1289–93.

    Article  PubMed  CAS  Google Scholar 

  5. Brey RL, Abbott RD, Curb JD, et al. Beta(2)-glycoprotein 1–dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the Honolulu Heart Program. Stroke. 2001;32:1701–6.

    Article  PubMed  CAS  Google Scholar 

  6. Sletnes KE, Smith P, Abdelnoor M, et al. Antiphospholipid antibodies after myocardial infarction and their relation to mortality, reinfarction, and non-haemorrhagic stroke. Lancet. 1992;339:451–3.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. Ginsburg KS, Liang MH, Newcomer L, et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med. 1992;117:997–1002.

    PubMed  CAS  Google Scholar 

  9. Finazzi G, Brancaccio V, Moia M, et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a 4-year prospective study from the Italian Registry. Am J Med. 1996;100:530–6.

    Article  PubMed  CAS  Google Scholar 

  10. Levine SR, Salowich-Palm L, Sawaya KL, et al. IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study. Stroke. 1997;28:1660–5.

    Article  PubMed  CAS  Google Scholar 

  11. Brey RL, Chapman J, Levine SR, et al. Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002. Lupus. 2003;12:508–13.

    Article  PubMed  CAS  Google Scholar 

  12. Ruiz-Irastorza G. The treatment of antiphospholipid syndrome: a harmonic contrast. Best Pract Res Clin Rheumatol. 2007;21:1079–92.

    Article  PubMed  CAS  Google Scholar 

  13. Brey RL, Stallworth CL, McGlasson DL, et al. Antiphospholipid antibodies and stroke in young women. Stroke. 2002;33:2396–401.

    Article  PubMed  CAS  Google Scholar 

  14. • Urbanus RT, Siegerink B, Roest M, 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;8:998–1005. This large case–control study showed that LA is a major risk factor for arterial thrombosis in women, and the presence of other risk factor increases the risk even further.

    Article  PubMed  CAS  Google Scholar 

  15. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:227–76.

    Article  PubMed  Google Scholar 

  16. Brey RL, Muscal E, Chapman J. Antiphospholipid antibodies and the brain: a consensus report. Lupus. 2011;20:153–7.

    Article  PubMed  CAS  Google Scholar 

  17. Tuthill JI, Khamashta MA. Management of antiphospholipid syndrome. J Autoimmune. 2009;33:92–8.

    Article  CAS  Google Scholar 

  18. de Lau LM, Leebeek FW, de Maat MP, et al. A review of hereditary and acquired coagulation disorders in the aetiology of ischaemic stroke. Int J Stroke. 2010;5:385–94.

    Article  PubMed  Google Scholar 

  19. •• 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. This is the latest consensus document following a systematic and critical review of the literature on primary and secondary thromboprophylaxis in individuals with aPLs.

    Article  PubMed  CAS  Google Scholar 

  20. Ortel TL: Thrombosis and the antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program 2005; 462–8.

  21. Erdogan D, Goren MT, Diz-Kucukkaya R, Inanc M. Assessment of cardiac structure and left atrial appendage functions in primary antiphospholipid syndrome: a transesophageal echocardiographic study. Stroke. 2005;36:592–6.

    Article  PubMed  Google Scholar 

  22. • Koniari I, Siminelakis SN, Baikoussis NG, et al.: Antiphospholipid syndrome; its implication in cardiovascular diseases: a review. J Cardiothorac Surg 2010;5:101. This is a good review of cardiac disease in APS.

    Article  PubMed  Google Scholar 

  23. Turiel M, Sarzi-Puttini P, Peretti R, et al. Thrombotic risk factors in primary antiphospholipid syndrome: a 5-year prospective study. Stroke. 2005;36:1490–4.

    Article  PubMed  Google Scholar 

  24. •• Caplan LR. Overview of the evaluation of stroke In: UpToDate, Kasner SE(Ed), UpToDate, Waltham, MA, 2011. This is an excellent topic review for initial stroke evaluation.

  25. Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295:1050–7.

    Article  PubMed  CAS  Google Scholar 

  26. 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 syndrome. N Engl J Med. 2003;349:1133–8.

    Article  PubMed  CAS  Google Scholar 

  27. Muscal E, Brey RL. Antiphospholipid syndrome and the brain in pediatric and adult patients. Lupus. 2010;19:406–11.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    PubMed  Google Scholar 

  29. Ruiz-Irastorza G, Khamashta MA. The treatment of antiphospholipid syndrome: a harmonic contrast. Best Pract Res Clin Rheumatol. 2007;21:1079–92.

    Article  PubMed  CAS  Google Scholar 

  30. Hughes G. Rituximab in lupus and beyond: the state of the art. Lupus. 2009;18:639–44.

    Article  PubMed  CAS  Google Scholar 

  31. Bick RL, Rice J. Long-term outpatient dalteparin (fragmin) therapy for arterial and venous thrombosis: efficacy and safety—a preliminary report. Clin Appl Thromb Hemost. 1999;5:S67–71.

    Article  PubMed  CAS  Google Scholar 

  32. • 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 May 30. [Epub ahead of print]. This is the latest study of LMWH in APS.

  33. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.

    Article  PubMed  CAS  Google Scholar 

  34. Hurley D. FDA approval sought for rivaroxaban to prevent stroke in atrial fibrillation. Neurology Today. 2011;11:22–3.

    Google Scholar 

  35. •• Ahrens I, Lip GY, Peter K: What do the RE-LY, AVERROES and ROCKET-AF trials tell us for stroke prevention in atrial fibrillation? Thromb Haemost. 2011;105:574–8. This is a good summary of new oral anticoagulants.

    Article  PubMed  CAS  Google Scholar 

  36. Laino C. Apixaban outperforms aspirin in stroke prevention. Neurology Today. 2011;11(1):12–4.

    Google Scholar 

  37. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806–17.

    Article  PubMed  CAS  Google Scholar 

  38. Cohen H, Machin SJ. Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants. Lupus. 2010;19:486–91.

    Article  PubMed  CAS  Google Scholar 

  39. Pierangeli SS, Erkan D. Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet? Lupus. 2010;19:475–85.

    Article  PubMed  CAS  Google Scholar 

  40. •• Mehdi AA, Uthman I, Khamashta M: Antiphospholipid syndrome: pathogenesis and a window of treatment opportunities in the future. Eur J Clin Invest 2010;40:451–64. This is a good review of novel therapies for APS.

    Article  PubMed  CAS  Google Scholar 

  41. Kumar D, Roubey RA. Use of rituximab in the antiphospholipid syndrome. Curr Rheumatol Rep. 2010;12:40–4.

    Article  PubMed  CAS  Google Scholar 

  42. Kahn P, Ramanujam M, Bethunaickan R, et al. Prevention of murine antiphospholipid syndrome by BAFF blockade. Arthritis Rheum. 2008;58:2824.

    Article  PubMed  Google Scholar 

  43. Brey RL. New treatment option for the antiphospholipid antibody syndrome? More pleiotropic effects of the statin drugs. J Thromb Haemost. 2004;2:1556–7.

    Article  PubMed  CAS  Google Scholar 

  44. • Jajoria P, Murthy V, Papalardo E, et al.: Statins for the treatment of antiphospholipid syndrome? Ann NY Acad Sci 2009;1173:736–45. This is a comprehensive review of statin use in APS.

    Article  PubMed  CAS  Google Scholar 

  45. Belizna CC, Richard V, Thuillez C, et al. Insights into atherosclerosis therapy in antiphospholipid syndrome. Autoimmun Rev. 2007;7:46–51.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

Dr. Levine is supported by National Institutes of Health/National Heart, Lung, and Blood Institute grant no. 1R01 HL096944.

Disclosure

Dr. Levine has been compensated for reviewing aPL and APS cases for law offices and receives book royalties.

Drs. Panichpisal and Rozner reported no potential conflicts of interest relevant to this article.

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Authors and Affiliations

  1. Department of Neurology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 1213, Brooklyn, NY, 11203-2098, USA

    Kessarin Panichpisal, Eduard Rozner & Steven R. Levine

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  1. Kessarin Panichpisal
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  2. Eduard Rozner
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  3. Steven R. Levine
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Correspondence to Steven R. Levine.

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Panichpisal, K., Rozner, E. & Levine, S.R. The Management of Stroke in Antiphospholipid Syndrome. Curr Rheumatol Rep 14, 99–106 (2012). https://doi.org/10.1007/s11926-011-0223-5

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