Clonal Hematopoiesis Rates in a Recurrent Venous Thrombosis Population: A Prospective Pilot Study.

BackgroundApproximately 50% of venous thromboembolism (VTE) are unprovoked, and 30% recur, leading to significant patient morbidity. Clonal hematopoiesis (CH) are acquired hematopoietic mutations that increase the risk of cardiovascular disease and myeloid neoplasms. CH may be associated with VTE and/or a predictive risk factor for recurrent VTE.MethodsWe conducted the first prospective pilot single-center study for patients with VTE to assess rate of CH, VTE recurrence rate, and clinical outcomes. Subjects with prior VTE underwent blood sample collection and detailed history collection during routine clinic visits. Next generation sequencing of samples was performed with Ion Torrent instrument using a custom Ampliseq 25 gene panel. CH was defined as variant allele frequency (VAF) of 2.0% or greater (CH≥2%). CH with VAF detected between 0.1% to 2.0% were confirmed by random sampling via digital droplet polymerase chain reaction. Statistical analysis on VTE outcomes for CH≥2% and on micro-CH, (defined as CH with VAF of ≥ 0.1%), was performed.Results/Conclusions167 subjects were enrolled with median follow up of 400 days. Approximately half (45.5%) had history of recurrent VTE and 80% had unprovoked VTE at study enrollment. The CH≥2% rate detected was 13.2% in the study population. There were 9.5 recurrent VTE events per 100 person-years and 40.1 bleeding events per 100 person-years in this study. There were no significant associations between CH and VTE in this pilot study. Larger clinical studies are needed.