Abstract

Patients with myeloproliferative disorders (MPD) have an excess of thrombotic complications which is not fully corrected by normalisation of their elevated haematocrit or thrombocytosis. The mechanisms responsible for this are not completely understood but platelets, leucocytes and endothelial cells have all been implicated. Plasma microparticles are observed to be elevated in other diseases associated with thrombotic complications. We measured platelet (PMP), endothelial (EMP), red cell (RMP) and leucocyte (LMP) microparticles in patients with MPD compared to healthy controls. Microparticles, of less than 1μm were measured by flow cytometry on platelet poor plasma obtained from citrated peripheral blood samples. Subtypes were identified using fluorescent conjugated monoclonal antibodies; EMP CD31+CD42-, PMP CD31+42+, RMP Glycophorin A + and LMP CD45+ events. Absolute concentrations of microparticles per μl plasma were calculated using Trucount beads. Results are currently available for 27 MPD patients, 9 polycythaemia vera (PV), and 18 primary thrombocythaemia and 14 healthy controls. All patients except 1 PV were on current treatment with hydroxycarbamide and all but 3 were receiving aspirin. PMP and LMP were elevated in MPD patients compared to healthy controls, PMP 12432 (1653) v 2371 (278) per μl, mean (SEM) p<0.001, LMP 98.7 (14) v 62.6 (7.7) per μl, p=0.03. EMP were elevated in MPD patients at 202 (34) v 34 (14) per μl, p<0.001. There was no significant difference in RMP levels 646 (131) v 589 (241) per μl, p=0.84. There were no significant differences in MP numbers between the PT and PV patients or by Jak2 V617F mutation status. Platelet count (x109/l) was higher in the MPD patients, PT 503 (39) v PV 372 (43) v control 236 (12), all comparisons p<0.04. PMP/platelet count was calculated to adjust for this and the ratio remained elevated in the MPD patients, PV 28.5 (4.5) and PT 26.1 (3.7) v controls 9.9 (1.2), both p=<0.03. In conclusion, these results demonstrate that PMP, EMP and LMP are elevated in MPD despite standard treatment, with the PMP elevated disproportionately to the platelet count. This is further evidence for platelet activation, endothelial dysfunction and a role for leucocytes in the thrombotic risk of MPD and that the microparticles also play an active role in promoting the prothrombotic state.

Author notes

Disclosure: No relevant conflicts of interest to declare.