Association Between Clonal Hematopoiesis of Indeterminate Potential and Risk of Venous Thromboembolism: A Systematic...

Clonal hematopoiesis of indeterminate potential (CHIP), marked by age-related somatic mutations in hematopoietic cells, has been linked to cardiovascular disease. Given its shared risk profile with venous thromboembolism (VTE), we evaluated the association between CHIP and VTE.

Following PRISMA guidelines and registered in PROSPERO (CRD420251051168), we systematically searched PubMed, Embase, and Scopus for observational studies reporting quantitative associations between CHIP and VTE through April 2025. Adjusted hazard ratios (HRs) were pooled using a random-effects meta-analysis; heterogeneity was assessed via the I² statistic. Sensitivity (leave-one-out) and subgroup analyses by mutation type and thrombotic phenotype were conducted.

Four studies met the inclusion criteria. The pooled HR for VTE in CHIP carriers was 1.52 (95% CI: 1.00-2.30; p = 0.05) with moderate-to-high heterogeneity (I² = 75%). Subgroup analyses showed non-significant elevated risks for TET2 (HR 1.62), DNMT3A (HR 1.11), and ASXL1 (HR 1.20) mutations. For pulmonary embolism, the pooled HR was 1.62 (95% CI: 0.78-3.38; I² = 85%).

CHIP is associated with increased VTE risk, suggesting it may be a novel risk factor. However, heterogeneity and study design limitations underscore the need for prospective studies.