P212 | COMPARATIVE ANALYSIS OF MUTATION LANDSCAPE IN MPN PATIENTS WITH SPLANCHNIC VEIN THROMBOSIS AND OTHER VEIN THROMBOSES

Introduction: Myeloproliferative neoplasms (MPNs) are a main cause of splanchnic vein thrombosis (SVT), with JAK2V617F as a known risk factor. The impact of co-occurring mutations on thrombosis risk remains unclear. Methods: This retrospective study included two molecularly characterized MPN cohorts: one with SVT (MPN-SVT), and one with non-splanchnic thrombotic events (MPN-TE). Diagnoses followed 2022 WHO/ICC criteria. SVT types included Budd–Chiari syndrome, portal (PT), splenic (ST), and mesenteric (MT) thromboses. Only the first event (at or before diagnosis) was considered. All patients underwent mutational analysis for driver genes and targeted NGS of 40 myeloid-relevant genes from granulocyte DNA collected at diagnosis or first referral. Aim: To compare the molecular features of patients with SVT vs. other thrombotic events to identify potential molecular markers linked to site-specific thrombosis. Results: The study population included 90 MPN pts (52 MPN-SVT and 38 MPN-TE). MPN-SVT included ET (17.3%), PV (36.6%), PMF (36.5%), and sMF (11.5%). MPN-TE included ET (10.5%), PV (60.5%), and PMF (29%). In MPN-SVT, PT occurred in 61.5%, ST in 3.8%, BCS in 15.4%, and multiple sites in 19.3% (PT+ST+MT most common). In MPN-TE, DVT occurred in 50%, superficial in 5.3%, both in 15.8%, cerebral in 5.3%, and VT-NOS in 23.7%. MPN-SVT patients were significantly younger at diagnosis (median 48.8 vs. 63.2 years, p < 0.001) and more often female (73% vs. 44.7%, p = 0.006). JAK2 mutation was most common in both (82.7% vs. 89.5%), with no difference in allele burden (40.96% vs. 42.76%). From a hematological standpoint, platelet counts at diagnosis were lower in MPN-SVT (384 vs. 522 ×10⁹/L, p = 0.043). Among non-driver mutations, no significant differences were found in non-driver mutation frequencies: ASXL1 (7.7% vs. 7.9%, p = 0.97), DNMT3A (13.5% vs. 10.5%, p = 0.89), and TET2 (5.8% vs. 7.9%, p = 0.18). Overall, non-driver mutation presence was similar between groups (p = 0.30). Conclusion: In this cohort, patients with SVT were predominantly female and younger compared to those presenting with other types of venous thrombosis at diagnosis. Nevertheless, no significant differences were observed in the molecular profile, including both driver or other myeloid-gene mutations. Further molecular profiling is ongoing, and updated data from the extended cohort will be presented at the meeting.