Factor XII Deficiency and Thrombosis Risk: A Systematic Review and Meta-Analysis

Factor XII (FXII) initiates the intrinsic coagulation pathway. Despite its role in contact activation assays, FXII deficiency is not associated with bleeding. Experimental models suggest that FXII deficiency may protect against thrombosis, but human studies have produced conflicting results regarding its association with venous or arterial thromboembolic events.

A systematic review and meta-analysis were conducted according to PRISMA guidelines. Embase, PubMed, Web of Science, and the Cochrane Library were searched up to August 2025. Eligible studies evaluated FXII deficiency in patients with thromboembolic events, deep vein thrombosis (DVT) or myocardial infarction (MI), and compared them with controls. Study characteristics and risk estimates were extracted. Pooled risk ratios (RRs) and odds ratios (ORs) were calculated using random-effects models, and heterogeneity was assessed using the I² statistic.

Of the 1,048 records identified, six studies, including 5,003 individuals, met the inclusion criteria. Study sizes ranged from 488-1,509 participants and included two prospective and four retrospective studies. The primary meta-analysis (five studies; 1,704 cases and 1,790 controls) showed a pooled RR of 1.34 (95% CI: 0.99-1.81). A secondary analysis restricted to DVT (n = 1,144 per group) yielded an RR of 1.44 (95% CI: 0.88-2.36; I² = 54.7%). A third analysis pooling adjusted ORs from two studies showed no association (OR 1.03; 95% CI: 0.65-1.64).

FXII deficiency was not significantly associated with thromboembolic risk. While not a reliable clinical marker of thrombosis, FXII remains a potential therapeutic target.