Clonal Hematopoiesis in Venous Thromboembolism: An Emerging Risk Factor
Alessandro Pozzi1, Giorgio Rosati1, Isabella Russo1, Cristina Barale1, Marco De Gobbi1, Alessandro Morotti1*
1Dept of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the presence of somatic mutations in genes associated with myeloid neoplasms at a variant allele fraction ≥2% in the absence of overt hematologic disease. While CHIP has been extensively linked to atherosclerotic cardiovascular disease, its role in venous thromboembolism (VTE) has only recently begun to emerge. Several observational studies suggest that CHIP may represent a novel risk factor for VTE, although the strength and consistency of this association remain less robust than for arterial disease. In particular, mutations in genes such as JAK2 and TET2 appear to confer a higher thrombotic risk, whereas the contribution of other CHIP-associated mutations remains less clear. Limited evidence also suggests a potential role of CHIP in the development of chronic thromboembolic complications, including chronic thromboembolic pulmonary hypertension. Data regarding VTE at unusual sites are scarce but may carry important clinical implications. Notably, a high prevalence of CHIP—particularly JAK2 and DNMT3A mutations—has been observed in patients with idiopathic splanchnic vein thrombosis, suggesting that specific CHIP-associated mutations may contribute to distinct thrombotic phenotypes. Mechanistically, CHIP-related thrombosis is thought to arise from chronic low-grade inflammation, immune dysregulation, endothelial injury, and enhanced platelet and neutrophil activation. However, the relative contribution of different mutations and clonal characteristics remains incompletely understood. In this commentary, we review current evidence regarding the epidemiology and pathogenesis of CHIP-associated VTE and discuss potential implications for risk stratification, monitoring, and future therapeutic strategies.
DOI: 10.29245/2690-0009/2026/2.1314 View / Download Pdf