CoChat
Sign Up
Cited by 37Systemic Lupus Erythematosus ResearchAcute Ischemic Stroke ManagementBlood Coagulation and Thrombosis Mechanisms

Lupus anticoagulants and anti‐phospholipid antibodies as risk factors for a first episode of ischemic stroke

Open access
SAIDI, S., MAHJOUB, T., ALMAWI, W.Y.·2009·Journal of Thrombosis and Haemostasis
DOI 10.1111/j.1538-7836.2009.03446.x
Open this paper in CoChat — free accountOpen PDF

Abstract

Background Antiphospholipid antibodies (aPLA) and lupus anticoagulant (LAC) were shown to precipitate thromboembolic events. Their association with ischemic stroke remains to be seen. Objectives We investigated the contribution of LAC, and antibodies directed against the phospholipids cardiolipin (aCL), phosphatidylserine (aPS), and the phospholipid-dependent cofactors beta2-glycoprotein I and annexin V, to the risk for ischemic stroke. Patients/methods LAC and antibody levels were measured in 208 stroke patients and 203 age- and gender-matched control subjects. Results Positive LAC resulted in an increased risk for stroke [OR (95% CI) = 8.1 (2.4-27.5)]. Significant elevation in aPS IgG, aCL IgM and aCL IgG titers, and increased prevalence of elevated aPS IgG, aCL IgM and aCL IgG (based on P95 cutoff values of healthy individuals) were seen in patients. aPS IgG was associated with cardioembolic, whereas aCL IgG and IgM were elevated in lacunar, atherosclerotic and cardioembolic, and LAC positivity was documented only in lacunar stroke subtypes. The co-presence of LAC with a positive aCL IgM/IgG or aPS IgG did not affect the overall risk for stroke. Multivariate analysis confirmed the association of positive LAC with stroke [aOR (95% CI) = 9.7 (1.8-52.5)], and demonstrated a clear gradation of increasing risk of stroke associated with the four categories of aCL IgG and aPS IgG, and identified aCL IgM P95 as independent predictors of stroke after adjusting for potentially confounding covariates. Conclusions Our study demonstrates that the presence of LAC, and elevated aCL IgG and aPS IgG antibodies are risk factors for stroke.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1538-7836.2009.03446.x

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 33

  1. Stewart JA, Dundas R, Howard RS, Rudd AG, Wolfe CD. Ethnic differences in incidence of stroke: prospective study with stroke regis- ter. BMJ 1999; 318: 967-71.
  2. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE, the TOAST Investigators. Classification of subtype of acute ischemic stroke. Stroke 1993; 24: 35-41.
  3. Ariyaratnam R, Casas JP, Whittaker J, Smeeth L, Hingorani AD, Sharma P. Genetics of ischaemic stroke among persons of non- European descent: a meta-analysis of eight genes involving approxi- mately 32,500 individuals. PLoS Med 2007; 4: e131.
  4. Banerjee I, Gupta V, Ganesh S. Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta- analysis. J Hum Genet 2007; 52: 205-19.
  5. Voetsch B, Damasceno BP, Camargo EC, Massaro A, Bacheschi LA, Scaff M, Annichino Bizzacchi JM, Arruda VR. Inherited thrombo- philia as a risk factor for the development of ischemic stroke in young adults. Thromb Haemost 2000; 83: 229-33.
  6. Gao X, Yang H, Zhiping T. Association studies of genetic polymor- phism, environmental factors and their interaction in ischemic stroke. Neurosci Lett 2006; 398: 172-7.
  7. Janardhan V, Wolf PA, Kase CS, Massaro JM, DÕAgostino RB, Franzblau C, Wilson PW. Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack: the Framingham cohort and offspring study. Stroke 2004; 35: 736-41.
  8. Nojima J, Kuratsune H, Suehisa E, Kitani T, Iwatani Y, Kanakura Y. Strong correlation between the prevalence of cerebral infarction and the presence of anti-cardiolipin/beta2-glycoprotein I and anti-phos- phatidylserine/prothrombin antibodies -co-existence of these anti- bodies enhances ADP-induced platelet activation in vitro. Thromb Haemost 2004; 91: 967-76.
  9. Lien LM, Chen WH, Chiu HC, Pan WH, Chen JR, Bai CH. High titer of anticardiolipin antibody is associated with first-ever ischemic stroke in Taiwan. Cerebrovasc Dis 2006; 22: 225-30.
  10. Tuhrim S, Rand JH, Wu X, Horowitz DR, Weinberger J, Goldman ME, Godbold JH. Antiphosphatidyl serine antibodies are indepen- dently associated with ischemic stroke. Neurology 1999; 53: 1523-7.
  11. Gonzales-Portillo F, McIntyre JA, Wagenknecht DR, Williams LS, Bruno A, Biller J. Spectrum of antiphospholipid antibodies (aPL) in patients with cerebrovascular disease. J Stroke Cerebrovasc Dis 2001; 10: 222-6.
  12. Carreras LO, Forastiero RR, Martinuzzo ME. Which are the best biological markers of the antiphospholipid syndrome? J Autoimmun 2000; 15: 163-72.
  13. Luong TH, Rand JH, Wu XX, Godbold JH, Gascon-Lema M, Tuhrim S. Seasonal distribution of antiphospholipid antibodies. Stroke 2001; 32: 1707-11.
  14. Rand JH. Antiphospholipid antibody syndrome: new insights on thrombogenic mechanism. Am J Med Sci 1998; 316: 142-51.
  15. Schultz DR. Antiphospholipid antibodies: basic immunology and assays. Semin Arthritis Rheum 1997; 26: 724-39.
  16. Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995; 74: 1185- 90.
  17. 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: 189-93.
  18. Brey RL, Stallworth CL, McGlasson DL, Wozniak MA, Wityk RJ, Stern BJ, Sloan MA, Sherwin R, Price TR, Macko RF, Johnson CJ, Earley CJ, Buchholz DW, Hebel JR, Kittner SJ. Antiphospholipid antibodies and stroke in young women. Stroke 2002; 33: 2396-400.
  19. Tuhrim S, Rand JH, Wu XX, Weinberger J, Horowitz DR, Goldman ME, Godbold JH. Elevated anticardiolipin antibody titer is a stroke risk factor in a multiethnic population independent of isotype or degree of positivity. Stroke 1999; 30: 1561-5.
  20. Heinzlef O, Abuaf N, Cohen A, Amarenco P; French Study of Aortic Plaques in Stroke Group. Recurrent stroke and vascular events in elderly patients with anticardiolipin antibodies: a prospective study. J Neurol 2001;248: 373-9.
  21. Metz LM, Edworthy S, Mydlarski R, Fritzler MJ. The frequency of phospholipid antibodies in an unselected stroke population. Can J Neurol Sci 1998; 25: 64-9.
  22. Tanne D, DÕOlhaberriague L, Trivedi AM, Salowich-Palm L, Schultz LR, Levine SR. Anticardiolipin antibodies and mortality in patients with ischemic stroke: a prospective follow-up study. Neuroepidemiol- ogy 2002; 21: 93-9.
  23. Jerrard-Dunne P, Evans A, McGovern R, Hajat C, Kalra L, Rudd AG, Wolfe CD, Markus HS. Ethnic differences in markers of thrombophilia: implications for the investigation of ischemic stroke in multiethnic populations: the South London Ethnicity and Stroke Study. Stroke 2003; 34: 1821-6.
  24. Markus HS, Khan U, Birns J, Evans A, Kalra L, Rudd AG, Wolfe CD, Jerrard-Dunne P. Differences in stroke subtypes between black and white patients with stroke: the South London Ethnicity and Stroke Study. Circulation 2007; 116: 2157-64.
  25. Hajat C, Tilling K, Stewart JA, Lemic-Stojcevic N, Wolfe CD. Ethnic differences in risk factors for ischemic stroke: a European case-control study. Stroke 2004; 35: 1562-7.
  26. Jones JV, Eastwood BJ, Jones E, James H, Mansour M. Antiphosp- holipid antibodies in a healthy population: methods for estimating the distribution. J Rheumatol 1995; 22: 55-61.
  27. 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 Va¨sterbotten cohort project. Stroke 2000; 31: 1289-93.
  28. Triplett DA. Use of dilute Russell Viper Venom Time (dRVVT); its importance and pitfalls. J Autoimmun 2000; 15: 173-8.
  29. Toschi V, Motta A, Castelli C, Paracchini ML, Zerbi D, Gibelli A. High prevalence of antiphosphatidylinositol antibodies in young pa- tients with cerebral ischemia of undetermined cause. Stroke 1998; 29: 1759-64.
  30. Kahles T, Humpich M, Steinmetz H, Sitzer M, Lindhoff-Last E. Phosphatidylserine IgG and beta-2-glycoprotein I IgA antibodies may be a risk factor for ischaemic stroke. Rheumatology 2005; 44: 1161-5.
  31. Tombul T, Atbas C, Anlar O. Hemostatic markers and platelet aggregation factors as predictive markers for type of stroke and neurological disability following cerebral infarction. J Clin Neurosci 2005; 12: 429-34.
  32. Camerlingo M, Casto L, Censori B, Drago G, Frigeni A, Ferraro B, Servalli MC, Radice E, Mamoli A. Anticardiolipin antibodies in acute non-hemorrhagic stroke seen within six hours after onset. Acta Neurol Scand 1995; 92: 69-71.
  33. Zielin˜ska J, Ryglewicz D, Wierzchowska E, Lechowicz W, Hier DB, Czlonkowska A. Anticardiolipin antibodies are an independent risk factor for ischemic stroke. Neurol Res 1999; 21: 653-7.

Cited by

Sorted by citations

Authors
SAIDI, S., MAHJOUB, T., & ALMAWI, W. Y.
Affiliations
  • University of Monastir (TN)
  • Arabian Gulf University (BH)
Corresponding author
ALMAWI, W.Y.
ORCID
Venue
Journal of Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2009-07
Volume
7
Issue
7
Pages
1075-1080
ISSN
1538-7836 (ISSN-L)
DOI
10.1111/j.1538-7836.2009.03446.x
OpenAlex
W2017176703
Cited by
37
References
3
Citations by year
2026: 2 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 1 · 2018: 1 · 2016: 4 · 2014: 1 · 2013: 1 · 2012: 6
FWCI
2.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thrombosis and Haemostasis (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
lupus anticoagulant, antiphospholipid antibodies, ischemic stroke, anticardiolipin antibodies, phosphatidylserine antibodies, beta2-glycoprotein I, annexin V, stroke risk factors, cardioembolic stroke, lacunar stroke, thromboembolism
MeSH terms
Aged, Brain Ischemia, Female, Humans, Male, Middle Aged, Regression Analysis, Retrospective Studies, Risk Factors, Case-Control Studies, Lupus Coagulation Inhibitor, Antibodies, Antiphospholipid, Stroke

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review