P127 | Clonal Hematopoiesis in Idiopathic Erythrocytosis and Thrombotic Risk Assessment
Year: 2025
Type: article
Abstract: Background: Idiopathic erythrocytosis (IE) is characterized by an increase in red blood cell mass without an identified cause. Diagnosis of IE is based on exclusion of all the known forms of primary and secondary acquired or congenital erythrocytosis. Recent studies showed a genetic complexity of IE, identifying a germinal origin in up to 70% of patients (pts). In the remaining cases a clonal hematopoiesis (CH) could be present but its role in thrombotic risk is still unclear Aims and methods: We investigated 79 IE pts referred to our division, with a complete medical history, including conventional cardiovascular risk factors (CRF) and thrombotic events (TE) before and after diagnosis. None of them carried JAK2 V617F or exon 12 mutations. In all pts next-generation sequencing (NGS) analysis was performed using DNA extracted from peripheral blood by the Myeloid Sophia Genetics Panel (30 genes) in order to identify somatic variants. All pts treated with phlebotomies to keep hematocrit (Ht) level below 50%, and received prophylaxis with low dose aspirin (ASA) according to prior thrombosis or concomitant CRF Results: Principal clinical and laboratory data of pts are shown in Table 1. We confirmed that most IE (55.5%) showed no evidence of CH. IE pts are more frequently males with normal EPO and ferritin level. However, 36 pts carried at least one somatic variant, principally involving DNMT3A, TET2 and ASXL1 genes. No significant differences in clinical and laboratory parameters were found when comparing the groups of pts with (NGS+) or without (NGS-) at least one somatic variant detectable, except for a higher median age at diagnosis (58.2 vs 47.2 years, p=0.0007) and a higher incidence of CRF (p=0.005) in NGS+ group. Therefore, the NGS+ pts received more ASA prophylaxis (p=0.002). After a median follow-up of 7.7 years, we observed 6 TE, 2 arterial (cardiac ischemia) and 4 venous (3 deep vein thrombosis, 1 pulmonary embolism) thrombosis in 4 pts, without significant difference according to NGS status Conclusion: In our IE series, the presence of CH is associated with advanced age and higher incidence of CRF at diagnosis, but doesn't seem to correlate with increased risk of TE. It is possible that our therapeutic strategy based on intensive phlebotomy (Ht target<50%) and stringent ASA prophylaxis influenced these results. Further and larger studies are need in order to achieve a more tailored thrombotic risk assessment and therapeutic approach in this setting
Authors: E.M. Elli, F. Cavalca, F. Mottadelli, V. Rago, B. Ferrari, G. Fazio, C. Gambacorti-Passerini, R. Piazza
Institution: University of Milano-Bicocca
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093121364
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