Platelet and Coagulation Activation in Myeloproliferative Diseases (MPD), and Relationship to JAK2(V617F) Mutation Status and Clonality.

Patients with MPD have an increased risk of thrombosis. Previous reports suggest an association between clonality and thrombosis in ET. The contribution of the JAK2 mutation to thrombotic risk is unclear. In our cohort of patients with MPD (n=122) (PRV n = 54, ET n = 64, IMF n= 4), we compared coagulation and platelet activation markers (D-Dimers, thrombin antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), soluble E-selectin(sE-selectin) and soluble P-selectin(sP-selectin)) between MPD patients and hypertensive controls. sP-selectin was significantly increased in patients with MPD (p=<0.001). The JAK2 mutation status was determined in our cohort by ARMS PCR. Of the total MPD cohort, 59% were JAK2 positive, (76% of PRV, 45% of ET, and 50% of IMF). Coagulation activation markers were compared in JAK2 positive and JAK2 negative patients. sP-selectin levels were highly significantly elevated in JAK2 positive patients compared to JAK2 negative (p= 0.002), or controls (p<0.001).

There was no significant difference in platelet count between JAK2 positive and negative patients (p=0.19). The clonality of the MPD was determined in 54 female patients using an x-chromosome inactivation pattern (XCIP) assay (HUMARA). A significant proportion of “polyclonal” patients, as defined by XCIPs were positive for the JAK2 mutation. We therefore calculated the proportion clonality of samples and found no correlation between proportion clonality and any coagulation or platelet activation marker.

Our results show an increase in platelet activation, as determined by sP-selectin levels, in patients with MPD compared to controls. Furthermore, platelet activation was a feature of patients positive for the JAK2 mutation when compared with wild type patients and controls. The role of the JAK2 mutation as a risk factor for thrombosis in MPD is still unclear but our study indicates that the presence of the mutation may be linked to platelet activation in MPD. Whether this translates into a higher clinical thrombosis risk requires further evaluation in a large prospective study.