The role of antiphospholipid antibodies in acute ischemic stroke

Abstract

Background & Objective: Antiphospholipid syndrome(APS) is one of the uncommon cause of ischemic stroke, and it has been known to be associated with young and female ischemic stroke patients. However, the significance of antiphospholipid antibody in older ischemic stroke patients are uncertain. We aimed to seek the significance of the APAs on ischemic stroke.

Materials and Methods: We consecutively collected 739 patients with acute ischemic stroke within 7 days of initial symptom from January 2016 to December 2018. We retrospectively obtained the clinical and laboratory data of the patients from medical records. APAs (lupus anticoagulant, anti-cardiolipin antibody, anti-β2 glycoprotein-I antibody) were measured the day after admission and the presence of at least one antibody was regarded as positive APA. For patients with positive APA, they were rechecked at least 12 weeks apart for confirmation of APS.

Result: Among 739 patients, 103 (13.9%) had positive APA initially. They were older, had more atrial fibrillation and had higher level of inflammatory markers. However, patients with APA had less diabetes mellitus. Stroke subtypes did not showed differences between two groups. Among 103 APA positive patients, 41 patients showed remained positive at 3 months, 23 patients showed negative conversion, and 39 patients were not available to check the follow up study. APS diagnosed patients had more number of APAs and higher anti-β2 glycoprotein-I IgG titers than negative conversion group. However, there were no significant differences of stroke subtypes between two groups. Presence of APA showed tendency to predict poor outcome of ischemic stroke in univariate analysis, but did not reached statistical significance in multivariable logistic regression analysis.

Conclusion: Our study found that APA is rather common antibodies in ischemic stroke patients regardless of age. Whether the influences of positive APA on ischemic stroke occurrence is not well known, two or more numbers of APAs and anti-β2 glycoprotein-I IgG titers may predict the presence of APS

|항인지질항체증후군은 기타 드문원인에 의해 발생되는 뇌경색 중 하나로 젊은 여성에게서 드물게 관찰된다. 하지만 장-노년층 뇌경색 환자의 항인지질항체 중요성은 아직 명확하지 않다. 따라서 급성 경색성 뇌졸중 환자에서 항인지질항체의 의미 및 중요성을 살펴보도록 하겠다.

한양대학교병원에 급성 경색성 뇌졸중 증상으로 증상 발생 후 7일 이내에 내원한 환자를 연속적으로 739명 모집하였으며, 모집기간은 2016년 1월부터 2018년 12월까지이다. 후향적으로 임상적 및 검사결과를 의무기록에서 취득하였으며 항인지질항체 (루푸스 항응고인자, 항카디오리핀 항체, 항베타2당단백1 항체) 는 입원 다음날 공복 후 혈액을 채취하여 검사하였다. 세 항체중 한 개 이상에서 양성을 보일 때 항인지질항체 양성으로 간주하였다. 양성이 나온 환자들은 항인지질항체증후군으로 확진하기 위해 최소 12주 이후에 재검사를 하였다.

739명의 환자 중 103명이 (13.9%) 첫 검사시 항인지질항체에서 양성을 보였으며, 음성을 보인 환자에 비해 나이가 많고 심방세동이 많으며 염증수치가 높았으며, 당뇨는 오히려 더 적은 환자에서 관찰되었다. 뇌졸중 유형에서는 통계적으로 차이를 보이지 않았다. 양성이 나온 103명의 환자 중 재검사 후 41명은 양성이 측정되었으며 23명은 음성으로 전환되었다. 두 환자군을 비교하였을 때 양성이 나온 환자군은 음성전환군보다 더 높은 항베타2 당단백1 항체 IgG 역가를 보였으며, 처음 검사시에 더 많은 양성의 항인지질항체 수를 가지고 있었으나 역시 뇌졸중 유형에서는 통계적으로 차이를 보이지 않았다. 단일변량분석에서는 항체의 존재가 뇌졸중환자의 예후와 밀접한 관련을 보였지만, 이분형회귀분석에서는 통계적 유의성을 보이지 않아 독립적인 위험요소를 만족하지 못하였다.

이 연구를 통해 항인지질항체는 특정 연령층과 무관하게 비교적 흔하게 관찰되는 항체임을 알 수 있다. 항인지질항체의 뇌졸중에 대한 영향은 아직 정확하지 않으며 2개 이상의 양성 항인지질항체 및 높은 항베타2당단백1 항체 역가는 훌륭한 항인지질항체증후군의 예측인자이다.; Background & Objective: Antiphospholipid syndrome(APS) is one of the uncommon cause of ischemic stroke, and it has been known to be associated with young and female ischemic stroke patients. However, the significance of antiphospholipid antibody in older ischemic stroke patients are uncertain. We aimed to seek the significance of the APAs on ischemic stroke.

Materials and Methods: We consecutively collected 739 patients with acute ischemic stroke within 7 days of initial symptom from January 2016 to December 2018. We retrospectively obtained the clinical and laboratory data of the patients from medical records. APAs (lupus anticoagulant, anti-cardiolipin antibody, anti-β2 glycoprotein-I antibody) were measured the day after admission and the presence of at least one antibody was regarded as positive APA. For patients with positive APA, they were rechecked at least 12 weeks apart for confirmation of APS.

Result: Among 739 patients, 103 (13.9%) had positive APA initially. They were older, had more atrial fibrillation and had higher level of inflammatory markers. However, patients with APA had less diabetes mellitus. Stroke subtypes did not showed differences between two groups. Among 103 APA positive patients, 41 patients showed remained positive at 3 months, 23 patients showed negative conversion, and 39 patients were not available to check the follow up study. APS diagnosed patients had more number of APAs and higher anti-β2 glycoprotein-I IgG titers than negative conversion group. However, there were no significant differences of stroke subtypes between two groups. Presence of APA showed tendency to predict poor outcome of ischemic stroke in univariate analysis, but did not reached statistical significance in multivariable logistic regression analysis.

Conclusion: Our study found that APA is rather common antibodies in ischemic stroke patients regardless of age. Whether the influences of positive APA on ischemic stroke occurrence is not well known, two or more numbers of APAs and anti-β2 glycoprotein-I IgG titers may predict the presence of APS