Pb2214: correlation between hemorrhagic events and ipset score in patients with essential thrombocythemia

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Essential thrombocythemia (ET) course is characterized by increased risk of thrombotic and hemorrhagic events, that represent their leading causes of mortality and morbidity. Treatment cornerstone are low dose aspirin and cytoreductive therapy, whose uses are proportionate to the risk of thrombosis assessed through IPSET score, the main thrombotic risk stratification tool among ET patients. Differently, there is no specific prognostic tool used to predict hemorrhagic risk in ET. Aims: The primary objective of this study was to analyze incidence and main risk factors connected to thrombotic and hemorrhagic events onset in ET patients, to provide correct prognostic stratification and optimize therapeutic strategies. Methods: We retrospectively analyzed distribution of clinical, biochemical, and molecular features among 308 patients diagnosed with ET between 1984 and 2002 and referred to the Hematology Department of Udine. Patients have been treated according to the current international guidelines. T-test and chi-squared test were performed to assess results. Results: Median age at ET diagnosis was 57.2 years (range: 17.7-87.6), with a slight prevalence of females (53.6%). According to mutational status, 201 patients (65.3%) were positive for V617F JAK2, 66 (21.4%) had a CALR mutation (type 1 in 40/66, 60.6%), and 14 (4.5%) had a MPL mutation (W515L in 12/14, 85.7%) while 21 patients (6.8%) were “triple negative”), while in 6 patients (2%) molecular analysis was not available. According to IPSET-thrombosis score, 49.7% patients were at high, 24.7% at intermediate and 25.6% at low risk, respectively. Nineteen patients (6.2%) presented an arterial or venous thrombotic event at ET diagnosis; 32 patients (10.4%) had a thrombotic event after diagnosis, after a median time of 92 months (range: 2-292): 25/32 were arterial events (10 pertaining the CNS, 8 the heart and 7 peripheral) and 7/32 were venous events (DVT). At thrombotic event, 26 patients were under cytoreductive therapy (HU in 21), 22 were in antiplatelet therapy (ASA in 20). Thrombosis-free survival (TFS) was significantly lower in high IPSET patients compared to intermediate or low risk, with a relative risk (RR) 4.1 times higher in high-risk patients compared to intermediate- or low-risk patients; estimated TFS at 10 and 20 years was 80.7% and 63.0% for high-risk, compared to 96.4% and 96.4% for intermediate-risk and 96.9% and 90.2% for low-risk, respectively (p <0.001. While we found no correlation between TFS and mutational status (p=0.18). Twenty-four patients (7.8%) experienced a hemorrhagic event after ET diagnosis, at a median time of 117 months (range: 1-316). At hemorrhage, 18 patients received cytoreduction (HU in 15), 19 antiplatelet therapy (ASA in 14) and 4 were under anticoagulants. As for thrombosis, there was a significant correlation between hemorrhagic risk and IPSET score: estimated HFS at 10 and 20 years was 90.2% and 75.0% for high-risk, compared to 97.1% and 97.1% for intermediate-risk and 96.8% and 96.8% for low-risk, respectively (p=0.002, Fig.1); RR for hemorrhage in high-risk patients was 3.3. Again, no correlation was found between hemorrhages and mutational status. Summary/Conclusion: Results of our analysis confirm the validity of IPSET score in predicting individual thrombotic risk among ET patients. More, a statistically significant correlation between the same score and hemorrhagic events incidence has been found, suggesting a possible role of IPSET scoring system as a global evaluator for vascular events.Keywords: Essential Thrombocytemia, Hemorrhage, Thromboembolic events