Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: A systematic review and meta-analysis of observational studies

Gili Kenet, Lisa K. Lütkhoff, Manuela Albisetti, Timothy Bernard, Mariana Bonduel, Leonardo Brandao, Stephane Chabrier, Anthony Chan, Gabrielle Deveber, Barbara Fiedler, Heather J. Fullerton, Neil A. Goldenberg, Eric Grabowski, Gudrun Günther, Christine Heller, Susanne Holzhauer, Alfonso Iorio, Janna Journeycake, Ralf Junker, Fenella J. KirkhamKarin Kurnik, John K. Lynch, Christoph Male, Marilyn Manco-Johnson, Rolf Mesters, Paul Monagle, C. Heleen Van Ommen, Leslie Raffini, Kevin Rostásy, Paolo Simioni, Ronald D. Sträter, Guy Young, Ulrike Nowak-Göttl*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

350 Citations (Scopus)


Background: The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies. Methods and results: A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: antithrombin deficiency, 7.06 (95% CI, 2.44 to 22.42); protein C deficiency, 8.76 (95% CI, 4.53 to 16.96); protein S deficiency, 3.20 (95% CI, 1.22 to 8.40), factor V G1691A, 3.26 (95% CI, 2.59 to 4.10); factor II G20210A, 2.43 (95% CI, 1.67 to 3.51); MTHFR C677T (AIS), 1.58 (95% CI, 1.20 to 2.08); antiphospholipid antibodies (AIS), 6.95 (95% CI, 3.67 to 13.14); elevated lipoprotein(a), 6.27 (95% CI, 4.52 to 8.69), and combined thrombophilias, 11.86 (95% CI, 5.93 to 23.73). In the 6 exclusively perinatal AIS studies, summary ORs were as follows: factor V, 3.56 (95% CI, 2.29 to 5.53); and factor II, 2.02 (95% CI, 1.02 to 3.99). Conclusions: The present meta-analysis indicates that thrombophilias serve as risk factors for incident stroke. However, the impact of thrombophilias on outcome and recurrence risk needs to be further investigated.

Original languageEnglish
Pages (from-to)1838-1847
Number of pages10
Issue number16
Publication statusPublished - 27 Apr 2010
Externally publishedYes

Bibliographical note

Sources of Funding
The study was supported by grants from the Förderverein “Schlaganfall und Thrombosen im Kindesalter e.V.,” Deutsche Schlaganfall-Hilfe, and Interdisziplinäres Zentrum für Klinische Forschung (CRA01-09), University of Münster. These study supporters had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Copyright © 2010 American Heart Association. All rights reserved.


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