A new study has shown that for patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), aspirin may restore expression of procaspase-activating compound 1 (PAC-1). The study’s results were presented in the British Journal of Haematology.

According to the researchers, previous research has shown the capacity of PAC-1 binding to be decreased in some patients with MPNs, particularly those with myelofibrosis.

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In this study, blood samples were analyzed from 40 patients with MPNs and compared with samples from healthy volunteers. Flow cytometry was used to measure expression of platelet fibrinogen receptors (PFRs) among study participants and with respect to whether patients were receiving low-dose aspirin (75 mg to 100 mg) for antiplatelet prophylaxis. Patients had never received cytoreductive therapies.

A total of 28 patients were receiving low-dose aspirin. In the 12 patients with MPNs who did not receive aspirin, PAC-1 binding to platelets was significantly reduced, at 35.3%, compared with 65.3% in the 10 healthy control individuals (P =.008). Patients receiving aspirin showed PAC-1 binding to platelets at a level (56.7%) that was more similar to that of healthy controls.

The researchers found that the JAK2 V617P mutation and corresponding allele burdens did not significantly influence PAC-1 binding capacity. However, in a subset of patients receiving aspirin who had no thrombosis history, persistent microcirculatory disorders were associated with greater PAC-1 binding compared with patients who were asymptomatic (67.7% vs 51.7%; P =.030).

The researchers concluded that low PAC-1 expression in untreated patients with MPNs can be enhanced with low-dose aspirin. “We hypothesize that the hypercoagulable states observed in these patients could depend on a primarily plasma-driven impairment of fibrin turnover and thrombin generation,” they explained.

Reference

1.     Lucchesi A, Carloni S, De Matteis S, et al. Unexpected low expression of platelet fibrinogen receptor in patients with chronic myeloproliferative neoplasms: how does it change with aspirin? [published online December 2, 2019]. Br J Haematol. doi:10.1111/bjh.16335