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Clinical Rheumatology

, Volume 38, Issue 2, pp 379–384 | Cite as

Stroke and antiphospholipid syndrome—antiphospholipid antibodies are a risk factor for an ischemic cerebrovascular event

  • Nataša GašperšičEmail author
  • Marjan Zaletel
  • Jan Kobal
  • Polona Žigon
  • Saša Čučnik
  • Snežna Sodin Šemrl
  • Matija Tomšič
  • Aleš Ambrožič
Original Article
  • 104 Downloads
Part of the following topical collections:
  1. Rheumatology in Slovenia: Clinical practice and translational research

Abstract

Testing for antiphospholipid antibodies could be an important part in determining the cause of a cerebrovascular event (CVE). Currently, it is also unknown whether antiphospholipid antibodies represent a risk factor for the development of a CVE and whether the selected therapy options are efficacious. So, this study aimed at (1) determining the frequency of patients experiencing a CVE and fulfilling the laboratory criterion for an antiphospholipid syndrome (APS), (2) investigating whether the persistent presence of antiphospholipid antibodies represented a risk factor for a CVE, and (3) focusing on the efficacy of the selected treatment strategy in the first year after the CVE. Eighty-nine patients with an acute CVE were prospectively followed for 1 year. At least two sera from each were tested for lupus anticoagulants, anticardiolipin, anti-β2-glycoprotein I, anti-phosphatidylserine/prothrombin and anti-annexin V antibodies. Twenty out of eighty-nine (22%) of CVE patients fulfilled the criteria for APS (17/20 for definitive and 3 for probable APS). There was a significant association between persistently present antiphospholipid antibodies and the CVE (OR, 4.62). No statistically significant difference was found in the CVE recurrence rate between APS-CVE and non-APS-CVE patients being treated mainly with acetyl salicylic acid. Antiphospholipid antibodies represent an independent risk factor for a CVE. In the first year after the CVE, antiplatelet therapy seemed to be sufficient in secondary CVE thromboprophylaxis in most APS patients.

Keywords

Antiphospholipid antibody Risk Stroke Treatment 

Notes

Funding information

The study was supported by the Slovenian Research Agency (ARRS) for the National Research Programme (P3-0314).

Compliance with ethical standards

Disclosures

None.

Ethics approval

The study was approved by the Slovene National Medical Ethics Committee (163/02/09).

References

  1. 1.
    Brey RL (2000) Differential diagnosis of central nervous system manifestations of the antiphospholipid antibody syndrome. J Autoimmun 15:133–138.  https://doi.org/10.1006/jaut.2000.0426 CrossRefGoogle Scholar
  2. 2.
    Shi H, Teng JL, Sun Y, Wu XY, Hu QY, Liu HL, Cheng XB, Yin YF, Ye JN, Chen PP, Yang CD (2017) Clinical characteristics and laboratory findings of 252 Chinese patients with anti-phospholipid syndrome: comparison with euro-phospholipid cohort. Clin Rheumatol 36:599–608.  https://doi.org/10.1007/s10067-017-3549-1 CrossRefGoogle Scholar
  3. 3.
    Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306.  https://doi.org/10.1111/j.1538-7836.2006.01753.x CrossRefGoogle Scholar
  4. 4.
    Bertolaccini ML, Hughes GR, Khamashta MA (2004) Revisiting antiphospholipid antibodies: from targeting phospholipids to phospholipid binding proteins. Clin Lab 50:653–665Google Scholar
  5. 5.
    Žigon P, Čučnik S, Ambrožič A, Kveder T, Šemrl SS, Rozman B, Božič B (2013) Detection of antiphosphatidylserine/prothrombin antibodies and their potential diagnostic value. Clin Dev Immunol 2013:1–8.  https://doi.org/10.1155/2013/724592 Google Scholar
  6. 6.
    Zhang S, Wu Z, Li J, Wen X, Li L, Zhang W, Zhao J, Zhang F, Li Y (2017) Evaluation of the clinical relevance of anti-annexin-A5 antibodies in Chinese patients with antiphospholipid syndrome. Clin Rheumatol 36:407–412.  https://doi.org/10.1007/s10067-016-3510-8 CrossRefGoogle Scholar
  7. 7.
    Bertolaccini ML, Amengual O, Atsumi T, Binder WL, de Laat B, Forastiero R, Kutteh WH, Lambert M, Matsubayashi H, Murthy V, Petri M, Rand JH, Sanmarco M, Tebo AE, Pierangeli SS (2011) ‘Non-criteria’ aPL tests: report of a task force and preconference workshop at the 13th International Congress on Antiphospholipid Antibodies, Galveston, TX, USA, April 2010. Lupus 20:191–205.  https://doi.org/10.1177/0961203310397082 CrossRefGoogle Scholar
  8. 8.
    Brandt JT, Triplett DA, Alving B, Scharrer I (1995) Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost 74:1185–1190CrossRefGoogle Scholar
  9. 9.
    Bozic B, Kveder T, Stegnar M, Morosini-Berus E, Kos-Golja M, Peternel P, Rozman B (1997) Influence of degraded phosphatidylserine on binding of antiphospholipid antibodies. Int Arch Allergy Immunol 112:19–26.  https://doi.org/10.1159/000237426 CrossRefGoogle Scholar
  10. 10.
    Cucnik S, Krizaj I, Rozman B, Kveder T, Bozic B (2004) Concomitant isolation of protein C inhibitor and unnicked beta2-glycoprotein I. Clin Chem Lab Med 42:171–174.  https://doi.org/10.1515/CCLM.2004.031 CrossRefGoogle Scholar
  11. 11.
    Žigon P, Ambrožič A, Čučnik S, Kveder T, Rozman B, Božič B (2011) Modified phosphatidylserine-dependent antiprothrombin [corrected] ELISA enables identification of patients negative for other antiphospholipid antibodies and also detects low avidity antibodies. Clin Chem Lab Med 49:1011–1018.  https://doi.org/10.1515/CCLM.2011.162 Google Scholar
  12. 12.
    Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24:35–41CrossRefGoogle Scholar
  13. 13.
    Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA, American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease (2014) Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:2160–2236.  https://doi.org/10.1161/STR.0000000000000024 CrossRefGoogle Scholar
  14. 14.
    Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D (2013) Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res (Hoboken) 65:1869–1873.  https://doi.org/10.1002/acr.22066 CrossRefGoogle Scholar
  15. 15.
    Sciascia S, Sanna G, Khamashta MA, Cuadrado MJ, Erkan D, Andreoli L, Bertolaccini ML, Action APS (2015) The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review. Ann Rheum Dis 74:2028–2033.  https://doi.org/10.1136/annrheumdis-2014-205663 CrossRefGoogle Scholar
  16. 16.
    Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL, American Heart Association Stroke Council (2018) 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49:e46–e110.  https://doi.org/10.1161/STR.0000000000000158 CrossRefGoogle Scholar
  17. 17.
    Delgado MG, Rodríguez S, García R, Sánchez P, Sáiz A, Calleja S (2015) Antiphospholipid syndrome of late onset: a difficult diagnosis of a recurrent embolic stroke. J Stroke Cerebrovasc Dis 24:e209–e211.  https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.04.016 CrossRefGoogle Scholar
  18. 18.
    Garcia D, Erkan D (2018) Diagnosis and management of the antiphospholipid syndrome. N Engl J Med 378:2010–2021.  https://doi.org/10.1056/NEJMra1705454 CrossRefGoogle Scholar
  19. 19.
    Pyo JY, Jung SM, Lee SW, Song JJ, Lee SK, Park YB (2017) Subsequent thrombotic outcomes in patients with ischemic stroke with antiphospholipid antibody positivity. Yonsei Med J 58:1128–1134.  https://doi.org/10.3349/ymj.2017.58.6.1128 CrossRefGoogle Scholar
  20. 20.
    Galli M, Luciani D, Bertolini G, Barbui T (2003) Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 101:1827–1832.  https://doi.org/10.1182/blood-2002-02-0441 CrossRefGoogle Scholar
  21. 21.
    Pengo V, Testa S, Martinelli I, Ghirarduzzi A, Legnani C, Gresele P, Passamonti SM, Bison E, Denas G, Jose SP, Banzato A, Ruffatti A (2015) Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant. Thromb Res 135:46–49.  https://doi.org/10.1016/j.thromres.2014.10.013 CrossRefGoogle Scholar
  22. 22.
    Pengo V, Denas G, Padayattil SJ, Zoppellaro G, Bison E, Banzato A, Hoxha A, Ruffatti A (2015) Diagnosis and therapy of antiphospholipid syndrome. Pol Arch Med Wewn 125:672–677Google Scholar
  23. 23.
    Yelnik CM, Urbanski G, Drumez E, Sobanski V, Maillard H, Lanteri A, Morell-Dubois S, Caron C, Dubucquoi S, Launay D, Duhamel A, Hachulla E, Hatron PY, Lambert M (2017) Persistent triple antiphospholipid antibody positivity as a strong risk factor of first thrombosis, in a long-term follow-up study of patients without history of thrombosis or obstetrical morbidity. Lupus 26:163–169.  https://doi.org/10.1177/0961203316657433 CrossRefGoogle Scholar
  24. 24.
    Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, Brey R, Crowther M, Derksen R, Erkan D, Krilis S, Machin S, Pengo V, Pierangeli S, Tektonidou M, Khamashta M (2011) 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 20:206–218.  https://doi.org/10.1177/0961203310395803 CrossRefGoogle Scholar
  25. 25.
    Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C (1994) Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Stroke 25:333–337CrossRefGoogle Scholar
  26. 26.
    Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirsh J, Douketis J, Laskin C, Fortin P, Anderson D, Kearon C, Clarke A, Geerts W, Forgie M, Green D, Costantini L, Yacura W, Wilson S, Gent M, Kovacs MJ (2003) A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 349:1133–1138.  https://doi.org/10.1056/NEJMoa035241 CrossRefGoogle Scholar
  27. 27.
    Okuma H, Kitagawa Y, Yasuda T, Tokuoka K, Takagi S (2009) 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 7:15–18Google Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Nataša Gašperšič
    • 1
    Email author
  • Marjan Zaletel
    • 2
  • Jan Kobal
    • 2
  • Polona Žigon
    • 1
  • Saša Čučnik
    • 1
    • 3
  • Snežna Sodin Šemrl
    • 1
    • 4
  • Matija Tomšič
    • 1
    • 5
  • Aleš Ambrožič
    • 1
  1. 1.Department of RheumatologyUniversity Medical Centre LjubljanaLjubljanaSlovenia
  2. 2.Department of NeurologyUniversity Medical Centre LjubljanaLjubljanaSlovenia
  3. 3.Faculty of PharmacyUniversity of LjubljanaLjubljanaSlovenia
  4. 4.Faculty of Mathematics, Natural Sciences and Information TechnologiesUniversity of PrimorskaKoperSlovenia
  5. 5.Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia

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