Inherited and acquired risk factors for arterial ischemic stroke in childhood

Abstract

Ischemic stroke in childhood is a rare but serious disorder, which is associated with significant morbidity and mortality. The lack of causal homogeneity in the aetiology of this disorder presents problems for predicting and preventing it, making the ischemic stroke in childhood a real dilemma for the clinician. Although a variety of potential inherited and acquired causes have been now identified, including cardiac pathologies, infections, prothrombotic, metabolic and vascular disorders, the aetiology of ischemic stroke in the young remains still unknown in more than one third of the patients. Presently, an appropriate evaluation of some hypercoagulable conditions seems justified in adults with stroke. However, the etiologic contribution of several thrombophilic conditions to initial and recurrent stroke in affected children has not been definitely clarified, since more powerful and influential non-thrombophilic risk factors are usually present, making the thrombophilia screening in such circumstance a matter of debate. In particular, the diagnostic yield of the screening is reportedly lower in children, the role of several prothrombotic abnormalities is uncertain, especially in recurrent stroke, and there is no evidence-based guidance to stroke prevention and therapy in children carrying a hypercoagulable state. Additional studies are needed to quantify the risk for a cerebrovascular event in children with a prothrombotic disorder and to determine which combination of endogenous and exogenous risk factors leads to greater rates of initial and recurrent stroke.

A Clinical Approach to Arterial Ischemic Childhood Stroke: Increasing Knowledge over the Last Decade

“…The risk for stroke in children is increased by the presence of additional factors such as hereditary coagulopathy. [57][58][59][60] The most relevant are antithrombin deficiency, protein C deficiency, elevated lipoprotein A, and antiphospholipid antibodies. Combination of the presence of hereditary coagulopathies doubles the risk of stroke.…”

Association of Polymorphisms in Coagulation Factor Genes and Enzymes of Homocysteine Metabolism With Arterial Ischemic Stroke in Children

“…Despite extensive investigation of potential additional risk factors, especially in the last 10 years, the etiology of AIS is still undetermined in up to 30% of children. 1,10,12,28,29…”

“…The best-studied genetic polymorphisms associated with an increased risk of AIS are factor V (FV) Leiden ( F5 1691 G>A, rs6025), factor II (FII) G20210A ( F2 20210 G>A, rs1799963), and the common polymorphism in the methylenetetrahydrofolate reductase [MTHFR] gene C677T ( MTHFR 677 C>T, rs1801131). 9 –13 Apart from them, only a few case–control studies have investigated the impact of other polymorphisms in coagulation and fibrinolysis factor genes in the etiology of AIS, such as FV HR2 haplotype ( F5 4070 A>G, rs1800595), β-fibrinogen (FBG)-455G>A ( FBG -455G>A, rs1800790), factor XIII-A (FXIII-A) p.Val34Leu ( F13A1 , rs5985), and plasminogen activator inhibitor 1 (PAI-1) 4G/5G ( SERPINE1 , rs1799889). 14 –19 The role of platelets is still relatively unknown as only the human platelet alloantigen 1 (HPA-1; ITGB3 , 176 T>C, rs5918) has been investigated among platelet glycoprotein receptor polymorphisms and conflicting results were reported.…”

Genotypes and phenotypes of protein S deficiency in Thai children with thromboembolism

“…In Asian populations with venous thromboembolism (VTE), prevalence rates of 8–30% have been reported, compared to 1–2% in Caucasian populations . PS deficiency is usually associated with VTE but less commonly in children with ischemic stroke . The PROS1 gene, located on chromosome 3q11.2, consists of 15 exons.…”