Journal of Thrombosis and Thrombolysis

, Volume 20, Issue 2, pp 105–112 | Cite as

Antiphospholipid Antibodies in Young Adults with Stroke



Background. Antiphospholipid antibodies have been associated with a clinical syndrome consisting thrombosis and recurrent, unexplained fetal loss.

Methods. The literature pertaining to stroke associated with antiphospholipid antibodies, with emphasis on stroke in young adults, was reviewed.

Results. Antiphospholipid antibodies are an independent risk factor for stroke in young adults in five of six studies. Multiple antiphospholipid specificities or the Lupus Anticoagulant were tested in addition to anticardiolipin antibody in these studies. In the single study that found no increased risk for stroke, only anticardiolipin antibody was tested. Only one of these studies evaluated for risk of recurrent stroke in young adults with antiphospholipid antibodies and found it to be increased. No treatment trials have been conducted in young adults with antiphospholipid antibodies and stroke. In the single treatment trial comparing aspirin and low-INR producing doses of warfarin to prevent recurrent stroke, both were found to be equally effective.

Conclusions. Antiphospholipid antibodies, particularly Lupus Anticoagulant, is an independent risk factor for first and possibly recurrent ischemic stroke in young adults. The best therapeutic strategy for preventing antiphospholipid antibody-associated recurrent stroke is not clear.

Key Words

antiphospholipid antibodies anticardiolipin antibody lupus anticoagulant antiphospholipid syndrome cerebral ischemia 


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  1. 1.
    Hughes GRV. Thrombosis, abortion, cerebral disease and lupus anticoagulant. Br Med J 1983;187:1088–1089.Google Scholar
  2. 2.
    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;2(7):1309–1311.CrossRefGoogle Scholar
  3. 3.
    Loizou S, McCrea JD, Rudge AC, Reynolds R, Boyle CC, Harris EN. Measurement of anticardiolipin antibodies by an enzyme linked immunosorbent assay (ELISA): standardization and quanitation of results. Clin Exp Immunol 1985;62:738–745.PubMedGoogle Scholar
  4. 4.
    Galli M, Comfurius P, Maassen C, et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990;335:1544–1547.CrossRefPubMedGoogle Scholar
  5. 5.
    Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin cofactors and the differential diagnosis of autoimmune disease. Lancet 1990;336(8708):177–178.CrossRefGoogle Scholar
  6. 6.
    Meroni PL, Del Papa N, Raschi E, et al. β 2 glycoprotein 1 as a co-factor for antiphospholipid reactivity with endothelial cells. Lupus 1998;7(2):S44–S47.PubMedGoogle Scholar
  7. 7.
    Miyakis S, Giannakopoulos B, Krillis SA. Beta 2 glycoprotein 1—function in health and disease. Thromb Haemostas 2004;114:335–346.CrossRefGoogle Scholar
  8. 8.
    Knic-Barrie S, Reister O'Connor C, Looney SW, Pierangeli SS, Harris EN. A retrospective review of 61 patients with antiphospholipid syndrome. Arch Intern Med 1997;157:2101–2108.CrossRefPubMedGoogle Scholar
  9. 9.
    Shah NM, Khamashta MA, Atsumi T, Hughes GRV. Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients. Lupus 1998;7:3–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Brey RL, Hart RG, Sherman DG, Tegeler CT. Antiphospholipid antibodies and cerebral ischemia in young people. Neurology 1990;40:1190–1196.PubMedGoogle Scholar
  11. 11.
    Nencini P, Baruffi MC, Abbate R, Massai G, Amaducci L, Inzitari D. Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischemia. Stroke 1992;23:189–193.PubMedGoogle Scholar
  12. 12.
    Toschi V, Motta A, Castelli C, Paracchini ML, Zerbi D, Gibelli A. High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause. Stroke 1998;29:1759–1764.PubMedGoogle Scholar
  13. 13.
    Singh K, Gaiha M, Shome DK, Gupta VK, Anuradha S. The association of antiphospholipid antibodies with ischemic stroke and myocardial infarction in young and their correlation: a preliminary study. J Assoc Physicians India 2001;49:537–529.Google Scholar
  14. 14.
    Brey RL, Stallworth CL, McGlasson DL, et al. Antiphospholipid antibodies and stroke in young women. Stroke 2002;33:2396–2400.CrossRefPubMedGoogle Scholar
  15. 15.
    Blohorn A, Guegan-Massardier E, Triquenot A, et al. Antiphospholipid antibodies in the acute phase of cerebral ischemia in young adults: a descriptive study of 139 patients. Cerebrovascular Dis 2002;13:156–162.CrossRefGoogle Scholar
  16. 16.
    Levine SR, Deegan MJ, Futrell N, Welch KMA. Cerebrovascular and neurologic disease associated with antiphospholipid antibodies: 48 cases. Neurology 1990;40: 1181–1189.PubMedGoogle Scholar
  17. 17.
    APASS. Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. Neurology 1993;43:2069–2073.Google Scholar
  18. 18.
    Levine SR, Brey RL, Sawaya KL, et al. Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome. Ann Neurol 1995;38:119–124.CrossRefPubMedGoogle Scholar
  19. 19.
    APASS. Anticardiolipin antibodies and the risk of recurrent thrombo-occlusive events and death. Neurology 1997;48:91–94.Google Scholar
  20. 20.
    Zielinska J, Ryglewicz D, Wierzchoska E, Lechowicz W, Hier DB, Czlonkiwska A. Anticardiolipin antibodies are an independent risk factor for ischemic stroke. Neurol Res 1999;21:653–657.PubMedGoogle Scholar
  21. 21.
    Tuhrim S, Rand JH, Wu X, et al. Elevated anticardiolipin antibody titer is an independent risk factor for stroke in a multiethnic population independent of isotype or degree of positivity. Stroke 1999;30:1561–1565.PubMedGoogle Scholar
  22. 22.
    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;32:1701–1706.PubMedGoogle Scholar
  23. 23.
    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.PubMedGoogle Scholar
  24. 24.
    Muir KW, Squire IB, Alwan W, Lees KR. Anticardiolipin antibodies in an unselected stroke population. Lancet 1994;344:452–456.CrossRefPubMedGoogle Scholar
  25. 25.
    Metz LM, Edworthy S, Mydlarski R, Fritzler MJ. The frequency of phospholipid antibodies in an unselected stroke population. Canadian Journal of Neurological Sciences 1998;25:64–69.PubMedGoogle Scholar
  26. 26.
    Tuhrim S, Rand JH, Wu X, et al. Antiphosphatidylserine antibodies are independently associated with ischemic stroke. Neurology 1999;53:1523–1527.PubMedGoogle Scholar
  27. 27.
    Tanne D, D'Olhaberriague L, Schultz LR, Salowich_Palm L, Sawaya KL, Levine SR. Anticardiolipin antibodies and their associations with cerebrovascular risk factors. Neurology 1999;52:1368–73.28.PubMedGoogle Scholar
  28. 28.
    Ahmed E, Stegmayr B, Trifunovic J, Weinehall L, Hallmans G, Lefvert AK. Anticardiolipin antibodies are not an independent risk factor for stroke. An incident case-referent study nested within the MONICA and Vasterbotten cohort project. Stroke 2000;31:1289–1293.PubMedGoogle Scholar
  29. 29.
    Tanne D, D'Olhaberriague L, Trivedi AM, Salowich-Palm L, Schyltz LR, Levine SR. Anticardiolipin antibodies and mortality in patients with ischemic stroke: a prospective follow-up study. Neuroepidemiology 2002;21:93–99.CrossRefPubMedGoogle Scholar
  30. 30.
    Cervera R, Piette J-C, 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;46:1019–1027.CrossRefPubMedGoogle Scholar
  31. 31.
    Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in Systemic Lupus Erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine 2003;82:299–308.CrossRefPubMedGoogle Scholar
  32. 32.
    Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in Systemic Lupus Erythematosus during a 5-year period: A multicenter prospective study of 1,000 patients. Medicine 1999;78:167–175.CrossRefPubMedGoogle Scholar
  33. 33.
    Carhuapoma JR, Mitsias P, Levine SR. Cerebral venous thrombosis and anticardiolipin antibodies. Neurology 1997;28:2363–2369.Google Scholar
  34. 34.
    Descheins M-A, Conard J, Horellou MH, et al. Coagulations studies, factor V Leiden, and anticardiolipin antibodies in 40 cases of cerebral venous sinus thrombosis. Stroke 1996:1724–1730.Google Scholar
  35. 35.
    Ameri A, Bousser MG. Cerebral venous thrombosis. Neurol Clin 1992;10:87–111.PubMedGoogle Scholar
  36. 36.
    Mackworth-Young C. Antiphospholipid syndrome: multiple mechanisms. Clin Exp Immunol 2004;136:393–401.CrossRefPubMedGoogle Scholar
  37. 37.
    Coull BM, Levine SR, Brey RL. The role of antiphospholipid antibodies and stroke. Neurol Clin 1992;10:125–143.PubMedGoogle Scholar
  38. 38.
    Antiphospholipid Antibodies in Stroke Study (APASS) Group. Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia. Stroke 1990;21:1268–1273.Google Scholar
  39. 39.
    Klemp P, Cooper RC, Strauss FJ, Jordaan ER, Przybojewski JZ, Nel N. Anticardiolipin antibodies in ischemic heart disease. Clin Exp Immunol 1988;74(2):254–257.PubMedGoogle Scholar
  40. 40.
    Ciocca RG, Choi J, Graham AM. Antiphospholipid antibodies lead to increased risk in cardiovascular surgery. Am J Surg 1995;170:198–200.CrossRefPubMedGoogle Scholar
  41. 41.
    Pierangeli SS, Vega-Ostertag M, Harris EN. Intracellular signaling triggered by antiphospholipid antibodies in platelets and endothelial cells: a pathway to therapies. Thromb Haemostas 2004;114:467–476.CrossRefGoogle Scholar
  42. 42.
    Meroni PL. Raschi E. Testoni C, et al. Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. Arthritis Rheum2001;44(12):2870–2878.CrossRefPubMedGoogle Scholar
  43. 43.
    Ford SE, Lillicrap DM, Brunet D, Ford PM. Thrombotic endocarditis and lupus anticoagulant, a pathogenetic possibility for idiopathic rheumatic type valvular heart disease. Arch Pathol Lab Med 1989;113:350–353.PubMedGoogle Scholar
  44. 44.
    Khamashta MA, Cervera R, Asherson RA, et al. Association of antibodies against phospholipids with valvular heart disease in patients with systemic lupus erythematosus. Lancet 1990; 335(8705):1541–1544.CrossRefPubMedGoogle Scholar
  45. 45.
    Cervera R. Coronary and valvular syndromes and antiphospholipid antibodies. Thromb Haemostas2004;114:501–508.CrossRefGoogle Scholar
  46. 46.
    Ford SE, Kennedy LA, Ford PM. Clinico-pathological correlations of antiphospholipid antibodies. Arch Path Lab Med 1994;118:491–495.PubMedGoogle Scholar
  47. 47.
    Gharavi AE, Peirangeli SS. Origin of antiphospholipid antibodies: Induction of aPL by viral peptides. Lupus 1998;7:S52–S54.CrossRefPubMedGoogle Scholar
  48. 48.
    Gharavi AE, Pierangeli SS, Colden-Stanfield M, Liu XW, Espinola RG, Harris EN. GDKV-induced antiphospholipid antibodies enhance thrombosis and activate endothelial cells in vivo and in vitro. Journal of Immunology1999;163(5):2922–2927.Google Scholar
  49. 49.
    Gharavi EE, Chaimovich H, Cucurull E, et al. Induction of antiphospholipid antibodies by immunization with synthetic viral and bacterial peptides. Lupus1999;8(6):449–455.PubMedGoogle Scholar
  50. 50.
    Gharavi AE, Pierangeli SS, Espinola RG, Liu X, Colden-Stanfield M, Harris EN. Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo. Arthritis Rheum2002;46(2):545–552.CrossRefPubMedGoogle Scholar
  51. 51.
    Drouvalakis KA, Buchanan TTC. Phospholipid specificity of autoimmune and drug induced lupus anticoagulants; association of phosphatidylethanolamine reactivity with thrombosis in autoimmune disease. J Rheumatol 1998; 25:290-295.PubMedGoogle Scholar
  52. 52.
    Vila P, Hernandez MC, Lopez-Fernandez MF, Batlle J. Prevalence, follow-up and clinical significance of the anticardiolipin antibodies in normal subjects. Thromb Haemostat 1994;72:209–213.Google Scholar
  53. 53.
    Campbell AL, Pierangeli SS, Wellhausen S, Harris EN. Comparison of the effects of anticardiolipin antibodies from patients with the antiphospholipid antibody syndrome and with syphilis on platelet activation and aggregation. Thromb Haemostat 1995;73:529–534.Google Scholar
  54. 54.
    Vasquez-Mellado J, Llorente L, Richaud-Patin Y, Alarcon-Segovia D. Exposure of anionic phospholipids upon platelet activation permits binding of beta-2-glycoprotein 1 and through it that of IgG antiphospholipid antibodies. J Autoimmunity 1994;7:335–348.CrossRefGoogle Scholar
  55. 55.
    Pierangeli SS, Harris EN. Antiphospholipid antibodies in an in vivo thrombosis model in mice. Lupus 1994;3:247-251.PubMedGoogle Scholar
  56. 56.
    Dagenais P, Urowitz MB, Gladman DD, et al. A family study of the antiphospholipid syndrome associated with other autoimmune diseases. J Rheumatol 1992;19:1393–1396.PubMedGoogle Scholar
  57. 57.
    Hudson N, Busque L, Rauch J, Kassis J, Fortin PR. Familial antiphospholipid syndrome and HLA-DRB gene associations. Arthritis, Rheumatism 1997;40:1907–1908.Google Scholar
  58. 58.
    Goel N, Ortel TL, Bali D, et al. Familial Antiphospholipid Antibody Syndrome Criteria for disease and Evidence for Autosomal Dominant Inheritance. Arthritis, Rheumatism 1999;42(2):318–327.Google Scholar
  59. 59.
    Goldstein R, Moulds JM, Smith CD, Senger DPS. Studies of primary antiphospholipid antibody syndrome and of antiphospholipid antibodies in Systemic Lupus Erythematosus. J Rheumatol 1996;23:1173–1179.PubMedGoogle Scholar
  60. 60.
    Csepany T, Bereczki D, Kollar J, Sikula J, Kiss E, Csiba L. MRI findings in central nervous system systemic lupus erythematosus are associated with immunoserological parameters and hypertension. J Neurol 2003;230:1348–1354.CrossRefGoogle Scholar
  61. 61.
    Provenzale JM, Heinz ER, Ortel TL, Macik BG, Charles LA, Alberts MJ. Antiphospholipid antibodies in patients without systemic lupus erythematosus: neuroradiologic findings. Radiology 1994;192:531–537.PubMedGoogle Scholar
  62. 62.
    Toubi E, Khamashta MA, Panarra A, Hughes GRV. Association of antiphospholipid antibodies with central nervous system disease in systemic lupus erythematosus. Am J Med 1995;99:397–401.CrossRefPubMedGoogle Scholar
  63. 63.
    Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–1277.PubMedGoogle Scholar
  64. 64.
    Tietjen GE, Day M, Norris L, et al. Role of anticardiolipin antibodies in young persons with migraine and transient focal neurologic events. Neurology 1998;50:1433–1440.PubMedGoogle Scholar
  65. 65.
    Sailer M, Burchert W, Ehrenheim C, et al. Positron emission tomography and magnetic resonance imaging for cerebral involvement in patients with systemic lupus erythematosus. J Neurol 1997;244:186–193.CrossRefPubMedGoogle Scholar
  66. 66.
    Schmidt R, Auer-Grumbach P, Fazekas F, Offenbacher H, Kapeller P. Anticardiolipin antibodies in normal subjects. Neuropsychological correlates and MRI findings. Stroke 1995;26:749–754.PubMedGoogle Scholar
  67. 67.
    Hachulla E, Michon-Pasturel U, Leys D, et al. Cerebral magnetic imaging in patients with or without antiphospholipid antibodies. Lupus 1998;7:124–131.CrossRefPubMedGoogle Scholar
  68. 68.
    Specker CH, Perniok A, Brauckmann, Siebler M, Schneider M. Detection of cerebral microemboli in APS—Introducing a novel investigation method and implications of analogies with carotid artery disease. Lupus 1998;7:S75–S80.CrossRefPubMedGoogle Scholar
  69. 69.
    Sun SS, Liu FY, Tsai JJP, Yen RF, Kao CH, Huang WS. Using 99mTc HMPAO brain SPECT to evaluate the effects of anticoagulant therapy on regional cerebral blood flow in primary antiphospholipid antibody syndrome patients with brain involvement—a preliminary report. Rheumatol Int 2003;23:301–304.CrossRefPubMedGoogle Scholar
  70. 70.
    Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid antibody syndrome. NEJM 1995;332:993–997.CrossRefPubMedGoogle Scholar
  71. 71.
    Rosove MH, Brewer PMC. Antiphospholipid thrombosis: Clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992;117:303–308.PubMedGoogle Scholar
  72. 72.
    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. NEJM 2003;349:1133–1138.CrossRefPubMedGoogle Scholar
  73. 73.
    APASS. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 2004;291:576–584.Google Scholar
  74. 74.
    Derksen RHWM, de Groot PG, Kappelle LJ. Low dose aspirin after ischemic stroke associated with antiphospholipid syndrome. Neurology 2003;61:111–114.PubMedGoogle Scholar
  75. 75.
    Ruiz-Ieastorza G, Khamashta KA, Hunt BJ, Escuedero A, Cuadrado MJ, Hughes GRV. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: An analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5. Arch Intern Med 2002;162:1164–1169.CrossRefPubMedGoogle Scholar

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© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.University of Texas Health Science Center at San AntonioSan AntonioUSA

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