Thrombophilia risk is not increased in children after perinatal stroke

Abstract

Key Points• Thrombophilia in children with perinatal stroke is rare, with rates similar to those in the normal population.• Routine testing in childhood is not indicated.Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders, but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management.We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias. Children with idiopathic magnetic resonance imaging-classified neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or fetal periventricular venous infarction (PVI) were recruited. Standardized thrombophilia evaluations were performed after 12 months of age on stroke cases and controls, including quantified proteins C and S, antithrombin, factors VIII/IX/XI, fibrinogen, lipoprotein(a), homocysteine, lupus anticoagulant, anticardiolipin antibodies and genotyping of factor V Leiden (FVL), factor II G20210A (FII), and methylenetetrahydrofolate reductase C677T. A total of 212 children were studied: 46 with NAIS, 34 with APPIS, 55 with PVI, and 77 controls (male, 53%; median age, 4.8 years). Of 14 parameters, no differences were observed in 12, including all common thrombophilias. Mean prothrombin time was shorter in arterial strokes (P < .001). Rates of antiphospholipid antibodies were low, comparable to those in controls, and resolved on repeat testing. FVL and FII rates were comparable to population norms. Total number of possible abnormalities did not differ between cases and controls. Our prospective, population-based, controlled, disease-specific study suggests minimal association between perinatal stroke and thrombophilia. This does not exclude the possibility of disordered coagulation at the time of stroke but suggests testing in childhood is not indicated. (Blood. 2017;129(20):2793-2800 Medscape Continuing

Arterial Ischemic Stroke Secondary to Cardiac Disease in Neonates and Children

“…29 The updated 2019 AHA guidelines for Management of Stroke in Neonates and Children 30 and the AHA Guidelines on Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease concur with these recommendations and suggest considering evaluation for inherited or acquired prothrombotic risk factors in children with heart disease who have a stroke (Class IIa, Level of Evidence B). 6 Although routine testing for hypercoaguability after neonatal stroke may not be indicated in the absence of cardiac disease, 31 in neonates and children with CHD, a thrombophilia evaluation may be appropriate. Consistent thrombophilia testing in children with cardiac disease may help identify children with additional risk factors for AIS who accordingly, should be considered for more intensive or longerterm antithrombotic treatment for primary or secondary AIS prevention.…”

Role of Perinatal Inflammation in Neonatal Arterial Ischemic Stroke

“…The only study which identified thrombophilia from genetic origin as an independent risk factor of neonatal ischemic stroke was based on a heterogeneous cohort of term, late preterm, and early preterm newborns ( 12 ). Several other studies assessed the association between constitutive prothrombotic risk factors and NAIS, with contradictory findings ( 23 – 25 ). The one with the most reliable methodology found a similar rate of thrombophilia at 12 months between the NAIS and the control groups ( 23 ).…”

Hemostasis in the Very Young

“…44 The potential association of thrombophilic risk factors and perinatal stroke notwithstanding, the causality of thrombophilia in the pathogenesis of AIS, deserves further attention. [48][49][50] One recent case-control study found that thrombophilia was not associated with risk for AIS during the perinatal period. 50 The number of patients in that study was small, however, and different stroke/CSVT entities were grouped together; thus, those findings should not be generalized prior to confirmation by other larger perinatal/neonatal cohorts.…”