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Stroke in children is a heterogeneous disorder. Over 100 risk factors for stroke have been reported and genetic predisposition to stroke has been established. The most frequently reported risk factors are congenital heart malformations, hemolytic anemias, collagen vascular diseases, some rare inborn metabolic disorders, trauma, infection and thrombophilia. The aim of this article is to provide an overview of investigated inherited prothrombotic risk factors in children with first ischemic stroke. Various prothrombotic risk factors have been investigated in pediatric stroke including elevated homocysteine and lipoprotein (a), antithrombin, protein C and protein S deficiency, Factor V Leiden, Factor II G20210A and plasminogen activator inhibitor-1 4G/5G polymorphism. Despite similar criteria for inclusion of different studies in meta-analyses investigating first ischemic stroke in children, the obtained results were not consistent for all prothrombotic risk factors. The discrepancies found could be explained by methodological issues like different sample sizes, patient populations included and lack of controls. In order to provide the necessary power for randomized control trials, multi-center, multi-national approaches like International Pediatric Stroke Study have been initiated with the aim to describe risk factors for childhood stroke and explore their relationship with presentation, age, geography, and infarct characteristics. Although it is evident from numerous studies that the frequency of inherited prothrombotic factors is increased in pediatric stroke, single thrombophilia does not fully explain stroke in a child as it represents only a mild risk factor. Further …