Platelet function studies in myeloproliferative neoplasms patients with Calreticulin or JAK2 V617F mutation

Alexandre Guy; Khalil Helzy; Olivier Mansier; Jean-Claude Bordet; Etienne Rivière; Mathieu Fiore; Chloe James

doi:10.1016/j.rpth.2023.100060

Platelet function studies in myeloproliferative neoplasms patients with Calreticulin or JAK2 ^V617F mutation

Res Pract Thromb Haemost. 2023 Jan 31;7(2):100060. doi: 10.1016/j.rpth.2023.100060. eCollection 2023 Feb.

Authors

Alexandre Guy^{1

2}, Khalil Helzy¹, Olivier Mansier^{1

2}, Jean-Claude Bordet³, Etienne Rivière⁴, Mathieu Fiore¹, Chloe James^{1

2}

Affiliations

¹ Laboratory of Hematology, University Hospital, Bordeaux, France.
² University of Bordeaux, INSERM UMR 1034, "Biology of Cardiovascular Diseases", Pessac, France.
³ Laboratory of Hematology, University Hospital of Lyon, Bron, France.
⁴ Internal Medicine and Infectious Diseases Unit, University Hospital, Bordeaux, France.

Abstract

Background: JAK2 ^V617F and Calreticulin (CALR) mutations are the most frequent molecular causes of Phi-negative myeloproliferative neoplasms (MPN). Patients with CALR mutations are at lower risk of thrombosis than patients with JAK2 ^V617F. We hypothesized that CALR-mutated blood platelets would have platelet function defects that might explain why these patients are at lower risk of thrombosis.

Objectives: Our main objective was to explore and compare platelet function depending on the MPN molecular marker.

Methods: We analyzed platelet function in 16 patients with MPN with CALR mutations and 17 patients with JAK2 ^V617F mutation and compared them with healthy controls. None of these patients was taking antiplatelet therapy. We performed an extensive analysis of platelet function and measured plasmatic soluble P-selectin and CD40L levels.

Results: We observed significant defects in platelet aggregation, surface glycoprotein expression, fibrinogen binding, and granule content in platelets from patients with MPN compared with that in controls. Moreover, soluble CD40L and P-selectin levels were elevated in patients with MPN compared with that in controls, suggesting an in vivo platelet preactivation. Comparison of platelet function between patients with CALR and JAK2 ^V617F MPN revealed only minor differences in platelets from patients with CALR. However, these results need to be interpreted within the context of absence of an inflammatory environment that could impact platelet function during MPN.

Conclusions: These results do not support the hypothesis that calreticulin-mutated platelets have platelet function defects that could explain the lower thrombotic risk of patients with CALR.

Keywords: JAK2V617F mutation; blood platelets; calreticulin; myeloproliferative neoplasms; platelet aggregation; thrombosis.