This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 118/13/1373    most recent CIRCULATIONAHA.108.789008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Young, G. Articles by Nowak-Göttl, U. Search for Related Content PubMed PubMed Citation Articles by Young, G. Articles by Nowak-Göttl, U. Related Collections Deep vein thrombosis Thrombophilia Thrombosis risk factors Related Article

(Circulation. 2008;118:1373-1382.)
© 2008 American Heart Association, Inc.

Vascular Medicine

Impact of Inherited Thrombophilia on Venous Thromboembolism in Children

A Systematic Review and Meta-Analysis of Observational Studies

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

From the Division of Hematology/Oncology, Children’s Hospital Los Angeles, Los Angeles, Calif (G.Y.); Division of Hematology, University Children’s Hospital, Zurich, Switzerland (M.A.); Servicio de Hematolgía y Oncología, Hospital de Pediatría "Prof. Dr. J.P. Garrahan," Buenos Aires, Argentina (M.B.); Hospital for Sick Children, Toronto, Canada (L.B.); McMaster University, Hamilton, Canada (A.C.); Leibniz Institute for Arteriosclerosis Research, University of Münster, Münster, Germany (F.F.); Department of Pediatrics, Hematology/Oncology/BMT, University of Colorado and the Children’s Hospital, Denver (N.A.G., M.M.-J.); Massachusetts General Hospital, Harvard Medical School, Boston, Mass (E.G.); Department of Pediatric Hematology/Oncology, University Hospital Frankfurt, Frankfurt, Germany (C.H.); Department of Pediatrics, Children’s Medical Centre Dallas, University of Texas Southwestern Medical Center, Dallas (J.J.); Israel National Haemophilia Centre, Sheba Medical Centre, Tel-Hashomer, Israel (G.K., A.L.); Department of Pediatric Hematology/Oncology, University Hospital Münster, Münster, Germany (A.K., U.N.-G.); Department of Pediatrics, University Hospital Munich, Munich, Germany (K.K.); Department for Pediatrics, Medical University, Vienna, Austria (C.M.); Department of Pediatrics, University of New Mexico, Albuquerque (P. Mathew); The Royal Children’s Hospital, Victoria, Australia (P. Monagle); Department of Pediatric Hematology, Emma Children’s Hospital AMC, Amsterdam, the Netherlands (H.v.O.); Department of Medical and Surgical Sciences, University of Padua, Padua, Italy (P. Simioni, D.T.); and Russian National Center of Pediatric Hematology/Oncology, Moscow State Medical University, Moscow, Russian Federation (P. Svirin).

Correspondence to Professor Dr U. Nowak-Göttl, Pediatric Hematology and Oncology, University Hospital of Münster, Albert-Schweitzer-Str 33, D-48149 Münster, Germany. E-mail leagottl{at}uni-muenster.de

Received January 3, 2008; accepted July 11, 2008.

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.

---

 

CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
Circulation 2008 118: 1307-1308. [Extract] [Full Text]

This article has been cited by other articles:

				L. Raffini, Y.-S. Huang, C. Witmer, and C. Feudtner Dramatic Increase in Venous Thromboembolism in Children's Hospitals in the United States From 2001 to 2007 Pediatrics, October 1, 2009; 124(4): 1001 - 1008. [Abstract] [Full Text] [PDF]

				U. Nowak-Gottl, H. Weiler, I. Hernandez, S. Thedieck, T. Seehafer, T. Schulte, and M. Stoll Fibrinogen {alpha} and {gamma} genes and factor VLeiden in children with thromboembolism: results from 2 family-based association studies Blood, August 27, 2009; 114(9): 1947 - 1953. [Abstract] [Full Text] [PDF]