VPB0758 - JAK2 V617F Confers Aspirin Resistance in Patients with Myeloproliferative Neoplasms

Background: Myeloproliferative neoplasms (MPNs) are a group of clonal disorders associated with an overproduction of differentiated haematopoietic stem cells (HSCs). Affected patients are at an increased risk of thrombosis. Despite treatment with aspirin, some patients still develop thrombotic phenomena whilst others develop major bleeding especially when subjected to surgical interventions.

Aims: Compare platelet aggregometry (PA) by Arachidonic Acid (AA) results of MPNs to healthy controls (HC) and to controls on aspirin (COA) therapy and assess the pharmacological response to aspirin by measuring the levels of thromboxane B2 (TXB2) in blood.

Methods: A total of 36 MPNs were recruited (17 JAK2 V617F positive and 19 JAK2 V617F negative), 22 HCs and 21 COAs. All subjects on aspirin were subjected to a 24 hour wash-out period. PA was performed using the PAP-8E Platelet Aggregation Profiler®. TXB2 was performed by an enzyme-linked immunosorbent assay (Cayman Chemical©).

Results: A statistical significant difference was detected between all 3 cohorts in AA maximum aggregation (MA) and TXB2. AA MA is slightly more supressed in COAs (mean 7.10) when compared to MPNs (mean 9.73), but both groups on aspirin have limited platelet function in response to AA when compared to HCs (mean 71.41). TXB2 levels were higher in MPNs (6469.71 pg/ml) when compared to the COA (445.08 pg/ml). When grouped by JAK2 status, no statistically significant differences were observed between JAK2+ve and JAK2-ve in AA MA, however differences were observed in TXB2, showing a higher mean in JAK2+ve (9605.94 pg/ml) when compared to JAK2-ve (3124.39 pg/ml).

Conclusion(s): JAK2 positivity confers aspirin resistance in MPNs, giving higher TXB2 values than JAK2-ve. This might in part explain the pathogenesis of higher risk of thrombosis in patients with JAK2 positivity.