Impact of Persistent Antiphospholipid Antibodies on Risk of Incident Symptomatic Thromboembolism in Children: A Systematic Review and Meta-Analysis

Gili Kenet; Sofia Aronis; Yackov Berkun; Mariana Bonduel; Anthony Chan; Neil A. Goldenberg; Susanne Holzhauer; Alfonso Iorio; Janna Journeycake; Ralf Junker; Christoph Male; Marilyn Manco-Johnson; Patti Massicotte; Rolf Mesters; Paul Monagle; Heleen van Ommen; Leslie Rafini; Paolo Simioni; Guy Young; Ulrike Nowak-Göttl

doi:10.1055/s-0031-1297171

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2011; 37(7): 802-809
DOI: 10.1055/s-0031-1297171

Impact of Persistent Antiphospholipid Antibodies on Risk of Incident Symptomatic Thromboembolism in Children: A Systematic Review and Meta-Analysis

Gili Kenet¹ , Sofia Aronis² , Yackov Berkun³ , Mariana Bonduel⁴ , Anthony Chan⁵ , Neil A. Goldenberg⁶ , Susanne Holzhauer⁷ , Alfonso Iorio⁸ , Janna Journeycake⁹ , Ralf Junker¹⁰ , Christoph Male¹¹ , Marilyn Manco-Johnson⁵ , Patti Massicotte¹² , Rolf Mesters¹³ , Paul Monagle¹⁴ , Heleen van Ommen¹⁵ , Leslie Rafini¹⁶ , Paolo Simioni¹⁷ , Guy Young¹⁸ , Ulrike Nowak-Göttl¹⁰

¹The Israel National Haemophilia Centre, Sheba Medical Centre, Tel-Hashomer, Israel
²Haemophilia Centre-Haemostasis Unit, Aghia Sophia Children's Hospital, Athens, Greece
³The Department of Pediatrics, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel
⁴Servicio de Hematolgía y Oncología, Hospital de Pediatría “Prof. Dr. JP Garrahan,” Buenos Aires, Argentina
⁵Thrombosis and Atherosclerosis Research Institute McMaster University, Hamilton, Ontario, Canada
⁶Department of Pediatrics and Medicine, Hematology/Oncology/BMT, University of Colorado and The Children's Hospital, Denver, Colorado
⁷Department of Pediatric Hematology/Oncology, Charite, Berlin, Germany
⁸Departments of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Ontario, Canada
⁹Department of Pediatrics, Children's Medical Centre Dallas, University of TX Southwestern, Medical Centre Dallas, Texas
¹⁰Department of Clinical Chemistry, University Hospital of Kiel, Kiel, Germany
¹¹Department for Pediatrics, Medical University Vienna, Vienna, Austria
¹²Department of Pediatrics, University Children Hospital Alberta, Canada
¹³Department of Internal Medicine, University Hospital of Münster, Münster, Germany
¹⁴The Royal Children's Hospital, Victoria, Australia
¹⁵Department of Pediatric Hematology, Emma Children's Hospital AMC, Amsterdam, The Netherlands
¹⁶Division of Hematology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
¹⁷Department of Medical & Surgical Sciences, University of Padua, Padua, Italy
¹⁸Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California

Abstract

ABSTRACT

The aim of this study was to estimate the impact of antiphospholipid (aPL) antibodies on the risk of incident thromboembolism (TE; arterial and venous) in children via meta-analysis of published observational studies. A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1966 to 2010 was conducted using keywords in combination both as MeSH terms and text words. Two authors independently screened citations and those meeting the a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, TE type, and frequency of recurrence were abstracted. Heterogeneity across studies was evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using either fixed-effects or random-effects models. Of 504, 16 pediatric studies met the inclusion criteria. In total 1403 patients and 1667 population-based controls ≤18 years were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. Thus, data from arterial and venous TE were analyzed together. In addition, meta-regression analysis did not reveal statistically significant differences between site of TE, age at first TE, country, or publication year. A statistically significant association with a first TE was demonstrated for persistent aPL antibodies, with an overall summary ORs/CI of 5.9/3.6–9.7 (arterial 6.6/3.5–12.4; deep vein thrombosis 4.9/2.2–10.9). The present meta-analysis indicates that detection of persistent aPL is clinically meaningful in children with, or at risk for, TE and underscores the importance of pediatric thrombophilia screening programs.

KEYWORDS

Antiphospholipid antibodies - thromboembolism - recurrence - children - meta-analysis

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Referenzen

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Ulrike Nowak-GöttlM.D.

Hemostasis Unit, Department of Clinical Chemistry, University Hospital of Kiel

Arnold-Heller-Str. 3, D-24105 Kiel, Germany

eMail: leagottl@gmail.com