© F e r r a t a S t o r t i F o u n d a t i o ntors include the relatively low incidence compared with that in adults, slow acceptance by some pediatricians of the increasing incidence of HA-VTE, lack of evidence on preventability, and -in particular -the paucity of studies applying appropriate methodologies for establishing independent risk factors and validating risk models derived from them. Challenges regarding how to best/consistently define a risk factor -e.g. immobility-also exist, as they do in adults.Lending further credence to the importance of developing evidence-based HA-VTE prevention guidelines for children, the International Society of Thrombosis and Haemostasis (ISTH) convened a Working Group, via the Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee Scientific and Standardization Committee (SSC), to develop recommendations for standardization and future research regarding pediatric HA-VTE risk factors and risk assessment models. As a prerequisite to the development of guidelines, current evidence must be rigorously analyzed. Accordingly, the purpose of this report is to present findings of a systematic review and metaanalysis of the literature on pediatric HA-VTE risk factors and risk-assessment models.
Methods
Search strategyWe identified English articles using PubMed (1946-May, 2014 and Embase (1980-May, 2014. The search strategies comprised "venous thromboembolism," "risk" and "children" with multiple subject headings and text-words per concept. Given the large body of VTE literature, we began with a sensitive query and progressively specified subsequent queries using major focus syntax and text-word title field restrictions. Selectively exploding subject headings, with relevant subcategories, permitted ever-increasing specificity. The full search strategy for Pubmed is available as Online Supplementary Table S1.
Study selectionWe excluded studies of patients older than 21 years based on the definition of pediatric age from the National Institute of Child Health and Human Development. 9 For studies that included pediatric and adult patients, we excluded those without clear subanalyses for patients under 21 years. Similarly, we excluded studies on arterial thromboembolism unless cases of VTE were included and clearly delineated in sub-analyses. Studies were categorized as narrative reviews, commentaries, single case reports, retrospective case series, cross-sectional studies, case-control studies, cohort studies (retrospective and prospective), registry studies, or clinical trials, the first three of which were excluded. Cases series were retained if they included at least 40 cases. Conflicting opinions regarding study design, where insufficiently or inconsistently described, were resolved through group consensus.
Data extractionThe following data were initially extracted by a pair of reviewers (BB, AM) and independently confirmed by a second pair (LR, CHvO): study design; number of patients/hospital unit; summary statistics on patients' age, gender; VTE location; time from VT...