Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐Analysis

Background Inherited thrombophilias are well‐established predisposing factors for venous thromboembolism, but their role in arterial thrombosis, such as arterial ischemic stroke, remains uncertain. We aimed to evaluate the association between inherited thrombophilia (factor V Leiden, prothrombin G20...

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Main Authors: Thita Chiasakul, Elizabeth De Jesus, Jiayi Tong, Yong Chen, Mark Crowther, David Garcia, Chatree Chai‐Adisaksopha, Steven R. Messé, Adam Cuker
Format: Article
Language:English
Published: Wiley 2019-10-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.119.012877
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author Thita Chiasakul
Elizabeth De Jesus
Jiayi Tong
Yong Chen
Mark Crowther
David Garcia
Chatree Chai‐Adisaksopha
Steven R. Messé
Adam Cuker
author_facet Thita Chiasakul
Elizabeth De Jesus
Jiayi Tong
Yong Chen
Mark Crowther
David Garcia
Chatree Chai‐Adisaksopha
Steven R. Messé
Adam Cuker
author_sort Thita Chiasakul
collection DOAJ
description Background Inherited thrombophilias are well‐established predisposing factors for venous thromboembolism, but their role in arterial thrombosis, such as arterial ischemic stroke, remains uncertain. We aimed to evaluate the association between inherited thrombophilia (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency) and risk of arterial ischemic stroke in adults. Methods and Results We searched PubMed, EMBASE, and Cochrane Library Databases from inception to December 31, 2018. We included case‐control or cohort studies of adults reporting the prevalence of inherited thrombophilias in those with arterial ischemic stroke and subjects without arterial ischemic stroke. Two reviewers (T.C., E.D.) independently searched the literature and extracted data. Pooled odds ratios (ORs) and 95% CIs were calculated using random‐effects model. We identified 68 eligible studies, which collectively enrolled 11 916 stroke patients and 96 057 controls. The number of studies reporting factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency were 56, 45, 15, 17, and 12, respectively. Compared with controls, patients with arterial ischemic stroke were significantly more likely to have the following inherited thrombophilias: factor V Leiden (OR, 1.25; 95% CI, 1.08–1.44; I2=0%), prothrombin G20210A mutation (OR, 1.48; 95% CI, 1.22–1.80; I2=0%), protein C deficiency (OR, 2.13; 95% CI, 1.16–3.90; I2=0%), and protein S deficiency (OR, 2.26; 95% CI, 1.34–3.80; I2=8.8%). Statistical significance was not reached for antithrombin deficiency (OR, 1.25; 95% CI, 0.58–2.67; I2=8.8%). Conclusions Inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, and protein S deficiency) are associated with an increased risk of arterial ischemic stroke in adults. The implications of these findings with respect to clinical management of patients with ischemic stroke require further investigation.
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spelling doaj-art-a02a3ceab3ac486a9067f5ff01ddccb52025-08-20T03:47:49ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802019-10-0181910.1161/JAHA.119.012877Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐AnalysisThita Chiasakul0Elizabeth De Jesus1Jiayi Tong2Yong Chen3Mark Crowther4David Garcia5Chatree Chai‐Adisaksopha6Steven R. Messé7Adam Cuker8Division of Hematology Department of Medicine Faculty of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital Thai Red Cross Society Bangkok ThailandTufts University School of Medicine Boston MADepartment of Biostatistics and Epidemiology Perelman School of Medicine University of Pennsylvania Philadelphia PADepartment of Biostatistics and Epidemiology Perelman School of Medicine University of Pennsylvania Philadelphia PADepartment of Medicine McMaster University Hamilton Ontario CanadaDepartment of Medicine University of Washington School of Medicine Seattle WAFaculty of Medicine Chiang Mai University Chiang Mai ThailandDepartment of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PADepartment of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PABackground Inherited thrombophilias are well‐established predisposing factors for venous thromboembolism, but their role in arterial thrombosis, such as arterial ischemic stroke, remains uncertain. We aimed to evaluate the association between inherited thrombophilia (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency) and risk of arterial ischemic stroke in adults. Methods and Results We searched PubMed, EMBASE, and Cochrane Library Databases from inception to December 31, 2018. We included case‐control or cohort studies of adults reporting the prevalence of inherited thrombophilias in those with arterial ischemic stroke and subjects without arterial ischemic stroke. Two reviewers (T.C., E.D.) independently searched the literature and extracted data. Pooled odds ratios (ORs) and 95% CIs were calculated using random‐effects model. We identified 68 eligible studies, which collectively enrolled 11 916 stroke patients and 96 057 controls. The number of studies reporting factor V Leiden, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency were 56, 45, 15, 17, and 12, respectively. Compared with controls, patients with arterial ischemic stroke were significantly more likely to have the following inherited thrombophilias: factor V Leiden (OR, 1.25; 95% CI, 1.08–1.44; I2=0%), prothrombin G20210A mutation (OR, 1.48; 95% CI, 1.22–1.80; I2=0%), protein C deficiency (OR, 2.13; 95% CI, 1.16–3.90; I2=0%), and protein S deficiency (OR, 2.26; 95% CI, 1.34–3.80; I2=8.8%). Statistical significance was not reached for antithrombin deficiency (OR, 1.25; 95% CI, 0.58–2.67; I2=8.8%). Conclusions Inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, protein C deficiency, and protein S deficiency) are associated with an increased risk of arterial ischemic stroke in adults. The implications of these findings with respect to clinical management of patients with ischemic stroke require further investigation.https://www.ahajournals.org/doi/10.1161/JAHA.119.012877hypercoagulopathystrokestroke, ischemicthrombosis
spellingShingle Thita Chiasakul
Elizabeth De Jesus
Jiayi Tong
Yong Chen
Mark Crowther
David Garcia
Chatree Chai‐Adisaksopha
Steven R. Messé
Adam Cuker
Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐Analysis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
hypercoagulopathy
stroke
stroke, ischemic
thrombosis
title Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐Analysis
title_full Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐Analysis
title_fullStr Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐Analysis
title_full_unstemmed Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐Analysis
title_short Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta‐Analysis
title_sort inherited thrombophilia and the risk of arterial ischemic stroke a systematic review and meta analysis
topic hypercoagulopathy
stroke
stroke, ischemic
thrombosis
url https://www.ahajournals.org/doi/10.1161/JAHA.119.012877
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