Impact of Inherited Thrombophilia on Symptomatic Venous Thrombo-Embolism (VTE) in Children: A Systematic Review & Meta-Analysis of 37 Studies Including 2470 Pediatric Patients.
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AbstractBackground: Inherited thrombophilia (IT) has been described as a risk factor for venous thromboembolism (VTE) in children. So far the majority of studies performed in the field were either retrospective or prospective on small numbers of patients. Thus, the results are contradictory or inconclusive mainly due to lack of statistical power. The aim of this study was to better estimate the impact of IT on early VTE onset and recurrence in children as a prerequisite to develop primary and secondary treatment options.Methods: A systematic search of publications listed in the electronic databases (Pubmed, Medline, EMBASE, Web of Science, The Cochrane Library) up to August 2007 using key words in combination both as MeSH terms and text words, was conducted. Citations were screened by two independent group members and those meeting the inclusion criteria were retained. Articles were included if published after 1990, when pediatric VTE was started to be systematically investigated.Findings: Twenty case-control and 17 cohort studies from 13 countries met the inclusion criteria. In these studies > 70% of patients had at least one clinical risk factor. The summary odds ratios (OR) and 95% confidence intervals (CI) of included studies under a fixed-effects and random-effects model showed statistically significant associations between the IT traits investigated and VTE onset (table). For the rare event of VTE recurrence, 1227 patients (eight studies) were evaluated: at the present state due to high heterogeneity, a trend towards association with recurrent VTE was found for ≥2 IT traits in the fixed-effects model (0R/CI: 2.8/1.6–4.8).Interpretation: The present meta-analysis gives evidence that the detection of inherited thrombophilia is clincially meaningful in children with VTE and underlines the importance of a pediatric thrombophilia screening program.Summary of Data Risk Factors OR/CI:fixed model OR/CI:random model patients/controls 2470/4119 N/A FV G1691A 3.5/2.9–4.2 3.2/2.3–4.4 FII G20210A 2.2/1.5–3.3 2.2/1.5–3.4 Protein C defiiciency 9.8/5.9–16 9.9/6.1–16.1 Protein S deficiency 7.1/3.9–13.2 6.8/3.7–12.7 Antithrombin deficiency 7.9/3.8–16.6 7.3/3.4–15.3 Lipoprotein(a) 4.4/3,2–5.9 4/2.4–6.6 ≥ 2 risk factors 12.6/7.3–21.8 11.6/6.2–20.2
