Role of factor VIII, IX, and XI in venous thrombosis recurrence risk in adults and children: A systematic review

BACKGROUND: Predicting recurrent venous thromboembolic events (VTEs) is challenging in clinical practice for both adults and children, but it is relevant for clinical management. Identifying laboratory risk factors for VTE recurrence may aid in clinical decision-making. OBJECTIVE: The goal of this systematic review is to investigate the predictive role of FVIII, IX, or XI in recurrent VTE in adult and pediatric patients with a first VTE. METHODS: A systematic review of the published literature was conducted in databases MEDLINE In-Process, Other Nonindexed Citations, MEDLINE Epub Ahead of Print, EMBASE Classic + EMBASE (OvidSP), and Cochrane (Wiley). We included observational and interventional studies that comprised adults or children with a first VTE, FVIII, FIX, and/or FXI and objectively confirmed VTE recurrence. The quality in prognosis studies tool was used to assess the risk of bias. RESULTS: We identified 2177 unique studies, of which 19 were included (18 for adults and 1 for children). The risk of bias was overall low to moderate. The studies were heterogenous with regards to population (provoked/unprovoked primary VTE), exposure (type of assay and cut-off values), and statistical analysis results (measures of association and modeling strategy). In adults, contradictory evidence was found for FVIII and FXI as outcome predictors, while no research could establish if FIX predicts VTE recurrence. Data in pediatrics were limited. Given the extensive heterogeneity of the literature, a meta-analysis was not performed. CONCLUSIONS: Overall, there is contradictory evidence that FVIII, FIX, or FXI predict recurrent VTE in adults and children. Addressing heterogeneity is a relevant aspect to consider in future studies investigating prognostic factors for VTE recurrence.