Skip to main content
Top
Published in: Current Rheumatology Reports 1/2012

01-02-2012 | ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)

The Management of Stroke in Antiphospholipid Syndrome

Authors: Kessarin Panichpisal, Eduard Rozner, Steven R. Levine

Published in: Current Rheumatology Reports | Issue 1/2012

Login to get access

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.
Literature
1.
go back to reference Lim W: Antiphospholipid antibody syndrome. Hematology Am Soc Hematol Educ Program. 2009, 233–9. Lim W: Antiphospholipid antibody syndrome. Hematology Am Soc Hematol Educ Program. 2009, 233–9.
2.
go back to reference Rodrigues CE, Carvalho JF, Shoenfeld Y. Neurological manifestations of antiphospholipid syndrome. Eur J Clin Invest. 2010;40:350–9.PubMedCrossRef Rodrigues CE, Carvalho JF, Shoenfeld Y. Neurological manifestations of antiphospholipid syndrome. Eur J Clin Invest. 2010;40:350–9.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
8.
go back to reference 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 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
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference Brey RL, Chapman J, Levine SR, et al. Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002. Lupus. 2003;12:508–13.PubMedCrossRef Brey RL, Chapman J, Levine SR, et al. Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002. Lupus. 2003;12:508–13.PubMedCrossRef
12.
go back to reference Ruiz-Irastorza G. The treatment of antiphospholipid syndrome: a harmonic contrast. Best Pract Res Clin Rheumatol. 2007;21:1079–92.PubMedCrossRef Ruiz-Irastorza G. The treatment of antiphospholipid syndrome: a harmonic contrast. Best Pract Res Clin Rheumatol. 2007;21:1079–92.PubMedCrossRef
13.
go back to reference Brey RL, Stallworth CL, McGlasson DL, et al. Antiphospholipid antibodies and stroke in young women. Stroke. 2002;33:2396–401.PubMedCrossRef Brey RL, Stallworth CL, McGlasson DL, et al. Antiphospholipid antibodies and stroke in young women. Stroke. 2002;33:2396–401.PubMedCrossRef
14.
go back to reference • 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. PubMedCrossRef • 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. PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference Brey RL, Muscal E, Chapman J. Antiphospholipid antibodies and the brain: a consensus report. Lupus. 2011;20:153–7.PubMedCrossRef Brey RL, Muscal E, Chapman J. Antiphospholipid antibodies and the brain: a consensus report. Lupus. 2011;20:153–7.PubMedCrossRef
17.
go back to reference Tuthill JI, Khamashta MA. Management of antiphospholipid syndrome. J Autoimmune. 2009;33:92–8.CrossRef Tuthill JI, Khamashta MA. Management of antiphospholipid syndrome. J Autoimmune. 2009;33:92–8.CrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference •• 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. PubMedCrossRef •• 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. PubMedCrossRef
20.
go back to reference Ortel TL: Thrombosis and the antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program 2005; 462–8. Ortel TL: Thrombosis and the antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program 2005; 462–8.
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference • 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. PubMedCrossRef • 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. PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference •• 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. •• 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.
go back to reference Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295:1050–7.PubMedCrossRef Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295:1050–7.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference Muscal E, Brey RL. Antiphospholipid syndrome and the brain in pediatric and adult patients. Lupus. 2010;19:406–11.PubMedCrossRef Muscal E, Brey RL. Antiphospholipid syndrome and the brain in pediatric and adult patients. Lupus. 2010;19:406–11.PubMedCrossRef
28.
go back to reference 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 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
29.
go back to reference Ruiz-Irastorza G, Khamashta MA. The treatment of antiphospholipid syndrome: a harmonic contrast. Best Pract Res Clin Rheumatol. 2007;21:1079–92.PubMedCrossRef Ruiz-Irastorza G, Khamashta MA. The treatment of antiphospholipid syndrome: a harmonic contrast. Best Pract Res Clin Rheumatol. 2007;21:1079–92.PubMedCrossRef
30.
31.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
32.
go back to reference • 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. • 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.
go back to reference Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.PubMedCrossRef Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.PubMedCrossRef
34.
go back to reference Hurley D. FDA approval sought for rivaroxaban to prevent stroke in atrial fibrillation. Neurology Today. 2011;11:22–3. Hurley D. FDA approval sought for rivaroxaban to prevent stroke in atrial fibrillation. Neurology Today. 2011;11:22–3.
35.
go back to reference •• 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. PubMedCrossRef •• 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. PubMedCrossRef
36.
go back to reference Laino C. Apixaban outperforms aspirin in stroke prevention. Neurology Today. 2011;11(1):12–4. Laino C. Apixaban outperforms aspirin in stroke prevention. Neurology Today. 2011;11(1):12–4.
37.
go back to reference Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806–17.PubMedCrossRef Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806–17.PubMedCrossRef
38.
go back to reference Cohen H, Machin SJ. Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants. Lupus. 2010;19:486–91.PubMedCrossRef Cohen H, Machin SJ. Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants. Lupus. 2010;19:486–91.PubMedCrossRef
39.
go back to reference Pierangeli SS, Erkan D. Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet? Lupus. 2010;19:475–85.PubMedCrossRef Pierangeli SS, Erkan D. Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet? Lupus. 2010;19:475–85.PubMedCrossRef
40.
go back to reference •• 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. PubMedCrossRef •• 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. PubMedCrossRef
41.
go back to reference Kumar D, Roubey RA. Use of rituximab in the antiphospholipid syndrome. Curr Rheumatol Rep. 2010;12:40–4.PubMedCrossRef Kumar D, Roubey RA. Use of rituximab in the antiphospholipid syndrome. Curr Rheumatol Rep. 2010;12:40–4.PubMedCrossRef
42.
go back to reference Kahn P, Ramanujam M, Bethunaickan R, et al. Prevention of murine antiphospholipid syndrome by BAFF blockade. Arthritis Rheum. 2008;58:2824.PubMedCrossRef Kahn P, Ramanujam M, Bethunaickan R, et al. Prevention of murine antiphospholipid syndrome by BAFF blockade. Arthritis Rheum. 2008;58:2824.PubMedCrossRef
43.
go back to reference Brey RL. New treatment option for the antiphospholipid antibody syndrome? More pleiotropic effects of the statin drugs. J Thromb Haemost. 2004;2:1556–7.PubMedCrossRef Brey RL. New treatment option for the antiphospholipid antibody syndrome? More pleiotropic effects of the statin drugs. J Thromb Haemost. 2004;2:1556–7.PubMedCrossRef
44.
go back to reference • 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. PubMedCrossRef • 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. PubMedCrossRef
45.
go back to reference Belizna CC, Richard V, Thuillez C, et al. Insights into atherosclerosis therapy in antiphospholipid syndrome. Autoimmun Rev. 2007;7:46–51.PubMedCrossRef Belizna CC, Richard V, Thuillez C, et al. Insights into atherosclerosis therapy in antiphospholipid syndrome. Autoimmun Rev. 2007;7:46–51.PubMedCrossRef
Metadata
Title
The Management of Stroke in Antiphospholipid Syndrome
Authors
Kessarin Panichpisal
Eduard Rozner
Steven R. Levine
Publication date
01-02-2012
Publisher
Current Science Inc.
Published in
Current Rheumatology Reports / Issue 1/2012
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-011-0223-5

Other articles of this Issue 1/2012

Current Rheumatology Reports 1/2012 Go to the issue

ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)

Drug-Induced Lupus Anticoagulants and Antiphospholipid Antibodies

ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)

Potential Use of Statins in the Treatment of Antiphospholipid Syndrome

ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)

Cognitive Dysfunction and Antiphospholipid Antibodies

SCLERODERMA (J VARGA, SECTION EDITOR)

Genetics of Systemic Sclerosis: An Update

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.