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Semin Thromb Hemost 2011; 37(7): 814-825
DOI: 10.1055/s-0031-1297173
© Thieme Medical Publishers

Safety and Efficacy of Low Molecular Weight Heparins in Children: A Systematic Review of the Literature and Meta-Analysis of Single-Arm Studies

Christoph Bidlingmaier1 , Gili Kenet2 , Karin Kurnik1 , Prasad Mathew3 , Daniela Manner4 , Lesley Mitchell5 , Anne Krümpel6 , Ulrike Nowak-Göttl4
  • 1Department of Thrombosis and Hemostasis, Dr. von Hauner's Children's Hospital, University Children's Hospital, Munich, Germany
  • 2Pediatric Coagulation Service, National Hemophilia Centre and Institute of Thrombosis and Hemostasis Sheba Medical Centre, Tel-Hashomer, Israel
  • 3Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico
  • 4Centre for Thrombosis and Hemostasis, Institute for Clinical Chemistry, University of Kiel, Kiel, Germany
  • 5Stollery Children's Hospital, University of Alberta, Edmonton AB, Canada
  • 6Department of Pediatric Hematology/Oncology, University Children's Hospital, University of Münster, Germany
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Publication Date:
20 December 2011 (online)

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ABSTRACT

Within the last two decades low molecular weight heparins (LMWH) have gained increasing widespread use as anticoagulants in children. The use of LMWH has been implemented into clinical care even though there is a lack of firm evidence on the efficacy and safety of LMWH in this population due to the absence of sufficiently powered randomized controlled trials. In the absence of clinical trials, we performed a meta-analysis of available single-arm studies using LMWH in children. A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1980 to 2010 was conducted using keywords in combination both as MeSH terms and text words. Two authors independently screened citations and those meeting a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients, ethnicity, venous thromboembolic events type, and frequency of recurrence and major bleedings were abstracted. Pooled incidence rates (IR) including 95% confidence intervals (95% CIs) on efficacy and safety data of LMWH administration on primary prophylaxis, as well as on secondary prophylaxis in children following symptomatic thromboembolism (TE) were shown. We included 2251 pediatric patients derived from 35 single-arm studies from 12 study countries who were eligible for analysis in the present systematic review. Pooled incidence rates (95% CI) to develop first TE on primary prophylaxis, further TE event on LMWH secondary prophylaxis, or a major bleeding event on LMWH were 0.047 (0.023 to 0.091), 0.052 (0.037 to 0.073) for efficacy, and 0.054 (0.039 to 0.074) for safety (treatment data only), respectively. Efficacy and safety data are comparable with adult data. The present systematic review suggests that use of LMWH in children as primary prophylaxis and in treatment of symptomatic thrombosis is effective and safe. However, properly designed randomized controlled trials are needed.

KEYWORDS

Low molecular weight heparin - pediatric thrombosis - children - safety and efficacy

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Christoph BidlingmaierM.D. 

Department of Thrombosis and Hemostasis, Dr. von Hauner's Children's Hospital

University Hospital, Lindwurmstr. 4, 80337 Munich

Email: christoph.bidlingmaier@med.uni-muenchen.de