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Ferrata Storti Foundation
Haematologica 2019 Volume 104(8):1676-1681
Hemostasis
Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population
Gabrielle deVeber,1* Fenella Kirkham,2,3* Kelsey Shannon,1 Leonardo Brandão,1 Ronald Sträter,4 Gili Kenet,5 Hartmut Clausnizer,6 Mahendranath Moharir,1 Martina Kausch,6 Rand Askalan,1 Daune MacGregor,1 Monika Stoll,7 Antje Torge,6 Nomazulu Dlamini,1 Vijeja Ganesan,2 Mara Prengler,2 Jaspal Singh3 and Ulrike Nowak-Göttl4/6
1The Hospital for Sick Children, Toronto, Canada; 2Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, London, UK; 3University Hospital Southampton, UK; 4Department of Paediatric Haematology/Oncology, University of Münster, Münster, Germany; 5Pediatric Coagulation Service, National Hemophilia Centre and Institute of Thrombosis and Hemostasis Sheba Medical Center, Tel-Hashomer, Israel; 6Institute of Clinical Chemistry, University Hospital Kiel-Lübeck, Kiel, Germany and 7Department of Genetic Epidemiology, University of Münster, Münster, Germany
*GdeV and FK contributed equally to this work.
ABSTRACT
Risk factors for arterial ischemic stroke in children include vasculopa- thy and prothrombotic risk factors but their relative importance to recurrent stroke is uncertain. Data on recurrent stroke from databases held in Canada (Toronto), Germany (Kiel-Lübeck/Münster), and the UK (London/Southampton) were pooled. Data were available from 894 patients aged 1 month to 18 years at first stroke (median age, 6 years) with a median follow-up of 35 months. Among these 894 patients, 160 (17.9%) had a recurrence between 1 day and 136 months after the first stroke (medi- an, 3.1 months). Among 288 children with vasculopathy, recurrence was significantly more common [hazard ratio (HR) 2.5, 95% confidence interval (95% CI) 1.92-3.5] compared to the rate in children without vasculopathy. Adjusting for vasculopathy, isolated antithrombin deficiency (HR 3.9; 95% CI: 1.4-10.9), isolated elevated lipoprotein (a) (HR 2.3; 95% CI: 1.3-4.1), and the presence of more than one prothrombotic risk factor (HR 1.9; 95% CI: 1.12-3.2) were independently associated with an increased risk of recur- rence. Recurrence rates calculated per 100 person-years were 10 (95% CI: 3-24) for antithrombin deficiency, 6 (95% CI: 4-9) for elevated lipoprotein (a), and 13 (95% CI: 7-20) for the presence of more than one prothrombotic risk factor. Identifying children at increased risk of a second stroke is impor- tant in order to intensify measures aimed at preventing such recurrences.
Introduction
Published estimates of the annual incidence of arterial ischemic stroke (AIS) in children range from 1.2 to 8 per 100,000 children.1-5 Prior diagnoses in children with symptomatic AIS are common and include cardiac disorders, hematologic condi- tions (sickle cell anemia, prothrombotic disorders), collagen tissue diseases, metabol- ic disorders, other chronic diseases, and acute illnesses.6-8 Childhood infections, including Varicella zoster virus, have been shown to be associated with an increased risk of AIS, with routine vaccination being protective against AIS.9,10 In addition, the presence of prothrombotic risk factors has been found in small case series and case control studies to be associated with ischemic stroke in children and this association has been confirmed by a meta-analysis.11 This is in contrast to perinatal stroke, in which recent studies have not shown an association with thrombophilia12 and recur- rence is relatively rare.13,14
Correspondence:
ULRIKE NOWAK-GÖTTL
leagottl@uksh.de
Received: November 7, 2018. Accepted: January 22, 2019. Pre-published: January 24, 2019.
doi:10.3324/haematol.2018.211433
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