Background: The two most frequent molecular causes of Phi negative myeloproliferative neoplasms (MPN) are JAK2V617F and mutations of Calreticulin. They are responsible for increased activation of the JAK/STAT pathway and subsequent increased production of platelets. The main risk in these diseases is thrombosis, but patients with Calreticulin mutations are at a lesser risk of thrombosis than JAK2V617F patients. The calreticulin protein, through its C domain, regulates calcium homeostasis. The mutations that are found in MPN impair this domain. Given the role of calcium in platelet activation, we hypothesized that calreticulin mutated platelets would have platelet function defects, that may explain why these patients are at lesser risk of thrombosis.

Aims: Compare platelet function depending on the molecular marker of MPN.

Methods: We analysed platelet function in 9 MPN patients with calreticulin mutations, 6 with JAK2V617F and 20 healthy controls. To rule out a possible effect of treatment on platelet function, none of the patients were taking antiplatelet therapy nor cytoreductive drugs.
We performed platelet agregometry, secretion assays, stained for glycoprotein receptor expression, analysed the content of alpha and dense granules, looked for phospholipid expression using annexin, and studied fibrinogen binding.

Results: We observed significant defects of platelet aggregation, secretion, CD41 expression, fibrinogen binding and dense granule content in calreticulin platelets compared with normal ones. But we also observed the same results with JAK2V617F platelets compared with normal ones. There was no significant difference in platelet function tests between calreticulin and JAK2 mutated platelets. We did not observe any significant difference in annexin binding among different subtypes of MPN platelets.

Conclusions: Using various platelet function tests, in patients without any antiplatelet nor cytoreductive treatment, we did observe platelet function defect in calreticulin mutated platelets but these defects were not specific for calreticulin mutations as we observed comparable defects in JAK2V617F platelets.

« Back to ISTH 2020 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-functions-defects-in-calreticulin-and-jak2v617f-mpn-patients/