Abstract Number: PB1225
Meeting: ISTH 2022 Congress
Background: Myeloproliferative neoplasms (MPN) includes polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Mutations in the calreticulin (CALR) gene were identified in patients with TE and PMF. Calreticulin, a chaperone protein, is involved in calcium homeostasis. CALR+ patients have fewer thrombotic complications than JAK2V617F+ patients.
Aims: As calcium plays a major role in platelet activation, we hypothesized that CALR+ patients have impaired platelet functions compared with JAK2V617F+ patients.
Methods: To assess platelet functions, we analyzed platelet aggregation, αIIbβ3 and GPIb expression, ATP secretion, fibrinogen binding, dense and alpha granule content, and phosphatidylserine (PS) expression. We used ELISA to measure two plasmatic platelets activation markers, soluble P-selectin (sCD62P) and CD40-ligand (CD40L).
Results: 33 MPN patients were included: 16 CALR+ and 17 JAK2V617F+ patients. None of them had antiplatelet therapy. We first observed a decreased aggregation in response to arachidonic acid in all MPN patients and a decreased aggregation in the presence of epinephrine and TRAP in CALR+ patients only. Expression of αIIbβ3 and internalization of GPIb was decreased in JAK2V617F+ and CALR+ patients compared to controls. Fibrinogen binding was also similarly decreased in CALR+ and JAK2V617F+ patients. Platelets P-selectin expression was decreased in JAK2V617F+ and CALR+ patients, as was the dense granule content. Interestingly, we observed PS overexpression in JAK2V617F+ patients, in favor of a procoagulant potential associated with JAK2V617F mutation. Together with this observation, we reported decreased PS exposure in hydroxyurea-treated patients compared to non-treated patients. Finally, plasmatic concentrations of sCD62P and CD40L were increased without difference between JAK2V617F+ and CALR+ patients.
Conclusion(s): We here report significantly altered platelet functions in CALR+ and JAK2V167F+ patients, but no difference between CALR+ and JAK2V167F+ patients. The presence of increased plasmatic concentrations of CD40L and sCD62 is in favor of in vivo platelet preactivation.
To cite this abstract in AMA style:Guy A, Fiore M, Helzy K, Mansier O, Bordet J, Riviere E, James C. Comparison of platelets function in patients with JAK2V617F or CALR mutated myeloproliferative neoplasms [abstract]. https://abstracts.isth.org/abstract/comparison-of-platelets-function-in-patients-with-jak2v617f-or-calr-mutated-myeloproliferative-neoplasms/. Accessed March 4, 2024.
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