Platelet function studies in myeloproliferative neoplasms patients with Calreticulin or JAK2V617F mutation

Background: JAK2V617F and Calreticulin (CALR) mutations are the most frequent molecularcauses of Phi-negative myeloproliferative neoplasms (MPN). Patients with CALRmutations are at lower risk of thrombosis than patients with JAK2V617F. We hypothesizedthat CALR-mutated blood platelets would have platelet function defects thatmight explain why these patients are at lower risk of thrombosis.Objectives: Our main objective was to explore and compare platelet functiondepending on the MPN molecular marker.Methods: We analyzed platelet function in 16 patients with MPN with CALR mutationsand 17 patients with JAK2V617F mutation and compared them with healthy controls.None of these patients was taking antiplatelet therapy. We performed an extensiveanalysis of platelet function and measured plasmatic soluble P-selectin and CD40Llevels.Results: We observed significant defects in platelet aggregation, surface glycoproteinexpression, fibrinogen binding, and granule content in platelets from patients with MPNcompared with that in controls. Moreover, soluble CD40L and P-selectin levels wereelevated in patients with MPN compared with that in controls, suggesting an in vivoplatelet preactivation. Comparison of platelet function between patients with CALR andJAK2V617F MPN revealed only minor differences in platelets from patients with CALR.However, these results need to be interpreted within the context of absence of aninflammatory environment that could impact platelet function during MPN.Conclusions: These results do not support the hypothesis that calreticulin-mutatedplatelets have platelet function defects that could explain the lower thrombotic riskof patients with CALR