Association between elevated plasma levels of factor VIII and risk of recurrent venous thromboembolism: a systematic review and meta-analysis.

Abstract

Although several studies have examined the relationship between factor VIII levels and recurrent venous thromboembolism (VTE), findings remain inconsistent. This systematic review and meta-analysis aimed to assess the association between elevated plasma factor VIII levels and VTE recurrence. A comprehensive search was conducted in PubMed, Web of Science, Scopus, and Embase databases, and Google Scholar up to May 2025 to identify observational studies evaluating the association between elevated factor VIII levels and recurrent VTE. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects model. Eighteen studies (12 cohort and 6 case-control studies) involving 9835 participants and 1554 recurrent events were included. Plasma factor VIII levels > 200 IU/dL were associated with an increased risk of VTE recurrence (RR = 1.70; 95% CI: 1.32-2.19; I² = 85.0%, P < 0.001). Subgroup analyses based on the type of effect measures indicated increased risk of VTE recurrence across studies reporting hazard ratios (HRs), odds ratios (Ors), and RRs. Similarly, the association remained significant in both cohort and case-control studies. Elevated factor VIII levels were associated with recurrence only in patients not receiving anticoagulation (RR = 1.64; 95% CI: 1.28-2.10), whereas no significant association was observed among those receiving anticoagulation (RR = 1.89; 95% CI: 0.36-9.87). This meta-analysis demonstrates a possible relationship between elevated factor VIII levels and VTE recurrence. These findings highlight the potential of factor VIII as a prognostic marker. Further prospective studies are needed to confirm this association and support clinical decision-making.