Presence of Extra-Criteria Antiphospholipid Antibodies Is an Independent Risk Factor for Ischemic Stroke

Naranjo, Laura; Ostos, Fernando; Gil‐Etayo, Francisco Javier; Hernández-Gallego, Jesús; Cabrera-Marante, Óscar; Pleguezuelo, Daniel; Díaz-Simón, Raquel; Cerro, Mercedes; Lora, David; Martínez-Salio, A; Serrano, Antonio

doi:10.3389/fcvm.2021.665741

Cited by 17 publications

(12 citation statements)

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“…This can result in embolic stroke or cause cardiac arrest or arrhythmia, cardiac output reduction secondary to myocardial infarction, or pericardial effusion, and lead to hypoperfusion stroke. Additionally, aPLs, which are present in 11%–40% of patients with SLE ( 24 , 25 ) and 17.2% in young patients (<50 years) with a stroke ( 26 ), are considered a cause of an acquired hypercoagulable state which can lead to ischemic stroke and TIA. aPLs comprise a heterogeneous group of autoantibodies, including mainly anti-β 2 -glycoprotein I antibody (aβ 2 -GPI), aCL, LA, and other antiphospholipid–protein antibodies.…”

Section: Discussionmentioning

confidence: 99%

Exploring the risk factors for ischemic cerebrovascular disease in systemic lupus erythematosus: A single-center case-control study

Zai-kang

Guan

et al. 2022

Front. Immunol.

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ObjectivesIschemic cerebrovascular disease (ICVD) is one of the most common and severe complications in systemic lupus erythematosus (SLE). We aim to explore the risk factors for ICVD in SLE and to assess their associated clinical characteristics.MethodsIn this study, 44 lupus patients with ICVD (ICVD-SLE) and 80 age- and sex-matched lupus patients without ICVD (non-ICVD-SLE) who were hospitalized in our center between 2014 and 2021 were enrolled. A comprehensive set of clinical and socio-demographic data was recorded. In the ICVD-SLE group, the modified Rankin score (mRS) at 90 days after the occurrence of ICVD, the brain MRI, and arterial ultrasonography findings were collected. Group comparisons were made with continuous variables using an independent t-test or the Mann–Whitney test, and with categorical variables using the chi-square test or Fisher exact test. Multivariate logistic regression analysis was performed to identify the risk factors for ICVD in SLE. Patients with ICVD-SLE were divided into three subgroups according to the gradations of intracranial arterial stenosis (ICAS). The subgroup comparisons were performed by one-way ANOVA test or Kruskal–Wallis test.ResultsOf the 44 patients with ICVD, 45% had a large-vessel ischemic stroke, 50% had a symptomatic lacunar stroke, and 9% had a transient ischemic attack. 2 (4.5%) had both large-vessel ischemic stroke and symptomatic lacunar stroke. Multivariate logistic regression analysis showed that cutaneous vasculitis (OR=7.36, 95% CI=2.11–25.65), anticardiolipin antibody (aCL) (OR=4.38, 95% CI=1.435–13.350), and lupus anticoagulant (LA) (OR=7.543,95% CI=1.789–31.808) were the risk factors, and hydroxychloroquine (HCQ) therapy (OR=0.198, 95% CI=0.078–0.502) was the protective factor, after controlling for confounders. During the analysis of the subgroups, no significant difference was observed between the patients in the group without internal carotid arterial occlusion (ICAS) and those with severe ICAS except for diagnostic delay. However, patients in the moderate ICAS group were older when SLE occurred (P<0.01), had a longer diagnostic delay (P<0.01), a lower percentage of hypocomplementemia (P=0.05) and steroids and HCQ therapy (P=0.01, P=0.05, respectively), a trend toward lower mRS score, but a higher incidence of carotid atherosclerotic plaque (P<0.01), when compared with the other two subgroups.ConclusionCutaneous vasculitis and antiphospholipid antibodies (aPLs) are associated with an increased risk of ICVD, while HCQ therapy may provide protection against ICVD in SLE. The ICVD in younger lupus patients is associated with complement-mediated inflammation and poorer outcome, and require immunosuppressive therapy, whereas the ICVD in elderly patients are characterized by moderate ICAS and carotid atherosclerotic plaques.

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Section: Discussionmentioning

confidence: 99%

Exploring the risk factors for ischemic cerebrovascular disease in systemic lupus erythematosus: A single-center case-control study

Zai-kang

Guan

et al. 2022

Front. Immunol.

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“…On the contrary, the clinical importance of IgA anti-β2GPI antibodies has increased over the last 16 years [ 7 ]. One cohort study by Tortosa et al followed up 244 patients who were positive for IgA-aβ2GPI without a history of APS-related symptoms for five years compared to 221 patients who tested negative for IgA-aβ2GPI.…”

Section: Discussionmentioning

confidence: 99%

Evidence of Thrombogenesis Recurrence Induced by IgA Antiphospholipid Antibody β2 Glycoprotein I-Dependent in Early Adulthood

Yacoub¹,

Khine²,

Najar³

et al. 2022

Cureus

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Antiphospholipid antibodies (aPLs) against Beta-2 glycoprotein-I (β 2 GPI) are considered to be the center of pathogenesis of antiphospholipid syndrome (APS). Autoimmune aPLs are pathogenic as patients are at increased risk of enhancing thrombin generation at a young age. There are only three aPLs considered as diagnostic laboratory markers for APS - IgM, IgG, and IgA isotypes. However, the association of the IgA isotypes with clinical thrombosis remains highly controversial. A 30-year-old male with a past medical history of childhood asthma initially presented to the hospital with acute left middle cerebral artery ischemic stroke, which did not get resolved with tissue plasminogen activator (tPA) but was successfully resolved with thromboembolectomy. It was speculated to be associated with a clot from mitral valve prolapse found subsequently on echocardiogram. Twenty-eight days later, the patient presented again with a high-grade luminal narrowing of his mid- and distal left internal carotid artery with 80% narrowing and an acute dissection of his left internal carotid artery. The recurrence of thrombosis was evaluated through hypercoagulable state workup, which demonstrated evidence of antiphospholipid syndrome with elevated beta-2 glycoprotein IgA antibody titers of more than 150 U/mL. This is one of the first cases reported nationwide as evidence of thrombogenesis recurrence induced by IgA antiphospholipid antibody β 2 glycoprotein I-dependent in early adulthood. IgA anti- β 2 GPI antibodies are found to have an association with many clinical manifestations of antiphospholipid syndrome and thrombotic events, particularly arterial thrombosis. To determine the link between the IgA-aβ 2 GPI antibodies and APS-events in asymptomatic individuals before recommending preventive treatments, there needs to be a broader intention to standardize IgA-aβ 2 GPI assays as a diagnostic criterion for APS.

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“…Cardiac embolism due to IE is an extraordinary stroke etiology, accounting for nearly 30% of all patients with IE ( 7 ). Non-infective endocarditis can complicate APS, which is a systemic autoimmune disease characterized by thrombotic complications in patients positive for aPL ( 5 , 8 , 9 ). The APS-associated non-infective endocarditis was reported to be Libman–Sacks (LS) endocarditis ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

A Cryptogenic Stroke Associated With Infective Endocarditis and Antiphospholipid Antibody Syndrome: Case Report and Literature Review

et al. 2022

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IntroductionAccurate definition of stroke etiology is crucial, as this will guide effective targets for treatment. Both antiphospholipid antibody syndrome (APS) and infective endocarditis (IE) can be independent risk factors for ischemic stroke in young adults. When an embolic stroke occurs with IE and APS simultaneously, the origin of the embolic source is difficult to identify.Case ReportA 19-year-old man was admitted to the hospital for the onset of stroke. A diagnosis of APS accompanied by IE was made after a series of examinations. We identified aortic valve vegetation as the embolic source. Although both APS and IE can induce valve vegetation, we considered IE to be the primary cause according to the infective clues. Despite treatment with ampicillin, the patient's fever persisted, and surgical aortic valve replacement was performed urgently. The patient recovered without recurrence of stroke during the 1-year follow-up.ConclusionA considerable challenge for physicians is evaluating all the signs suggestive of embolic sources in acute stroke and identifying the primary etiology when there are multiple causes. Early diagnosis and surgical intervention for bicuspid aortic valve (BAV) vegetation complicated by acute stroke may yield favorable clinical results.

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Presence of Extra-Criteria Antiphospholipid Antibodies Is an Independent Risk Factor for Ischemic Stroke

Cited by 17 publications

References 78 publications

Exploring the risk factors for ischemic cerebrovascular disease in systemic lupus erythematosus: A single-center case-control study

Exploring the risk factors for ischemic cerebrovascular disease in systemic lupus erythematosus: A single-center case-control study

Evidence of Thrombogenesis Recurrence Induced by IgA Antiphospholipid Antibody β2 Glycoprotein I-Dependent in Early Adulthood

A Cryptogenic Stroke Associated With Infective Endocarditis and Antiphospholipid Antibody Syndrome: Case Report and Literature Review

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