Impact of inherited thrombophilia on venous thromboembolism in children: A systematic review and meta-analysis of observational studies

Guy Young, Manuela Albisetti, Mariana Bonduel, Leonardo Brandao, Anthony Chan, Frauke Friedrichs, Neil A. Goldenberg, Eric Grabowski, Christine Heller, Janna Journeycake, Gili Kenet, Anne Krümpel, Karin Kurnik, Aaron Lubetsky, Christoph Male, Marilyn Manco-Johnson, Prasad Mathew, Paul Monagle, Heleen Van Ommen, Paolo SimioniPavel Svirin, Daniela Tormene, Ulrike Nowak-Göttl

Research output: Contribution to journalReview articlepeer-review

211 Scopus citations


Background - The aim of the present study was to estimate the impact of inherited thrombophilia (IT) on the risk of venous thromboembolism (VTE) onset and recurrence in children by a meta-analysis of published observational studies. Methods and Results - A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2007 was conducted using key words in combination as both MeSH terms and text words. Citations were independently screened by 2 authors, and those meeting the inclusion criteria defined a priori were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, VTE type, and frequency of recurrence were abstracted. Heterogeneity across studies was evaluated, and summary odds ratios and 95% CIs were calculated with both fixed-effects and random-effects models. Thirty-five of 50 studies met inclusion criteria. No significant heterogeneity was discerned across studies. Although >70% of patients had at least 1 clinical risk factor for VTE, a statistically significant association with VTE onset was demonstrated for each IT trait evaluated (and for combined IT traits), with summary odds ratios ranging from 2.63 (95% CI, 1.61 to 4.29) for the factor II variant to 9.44 (95% CI, 3.34 to 26.66) for antithrombin deficiency. Furthermore, a significant association with recurrent VTE was found for all IT traits except the factor V variant and elevated lipoprotein(a). Conclusions - The present meta-analysis indicates that detection of IT is clinically meaningful in children with, or at risk for, VTE and underscores the importance of pediatric thrombophilia screening programs.

Original languageEnglish (US)
Pages (from-to)1373-1382
Number of pages10
Issue number13
StatePublished - Sep 23 2008


  • Meta-analysis
  • Pediatrics
  • Recurrence
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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