Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation

Abstract

The development of thrombosis in polycythaemia vera (PV) involves multifactorial processes including pathological activation of blood cells. Release of microparticles (MPs) by activated cells in diseases is associated with thrombotic risk, but relatively few data are available in PV. The aim of the present study was to investigate the increase in MP release and exposure of phosphatidylserine (PS) on the outer membrane of MP-origin cells in patients with PV, and to analyse their procoagulant activity (PCA). PS-positive MPs and cells were detected by flow cytometry, while PCA was assessed with clotting time and purified coagulation complex assays. We found that PV patients had elevated circulating lactadherin+ MPs, which mostly originating from erythrocytes, platelets, granulocytes, and endothelial cells, as well as increased PS exposing erythrocytes/platelets as compared to secondary polycythaemia patients or healthy controls. These PS-bearing MPs and cells were highly procoagulant. Moreover, lactadherin competed factor V and VIII to PS and inhibited about 90% of the detected PCA in a dose-response manner while anti-TF antibody did no significant inhibition. Treatment with hydroxyurea is associated with a decrease in PS exposure and lactadherin+ MP release of erythrocytes/platelets. Our data demonstrate that PV patients are characterised by increased circulating procoagulant MPs and PS exposing erythrocytes/platelets, which could contribute to the hypercoagulable state in these patients.

Mechanisms of thrombogenesis in polycythemia vera

“…46 Among patients with PV, serum microparticles originating from platelets, erythrocytes, granulocytes, and ECs are elevated compared with healthy controls. 47, 48 In particular, patients with MPNs that had the JAK2 V617F mutation had significantly higher plasma concentrations of tissue factor–positive microparticles and erythrocyte microparticles ( P <0.05). 48 Among patients with MPNs, serum concentrations of platelet, erythrocyte, and EC microparticles were higher in patients with thrombotic complications ( P <0.05).…”

“…42 Furthermore, the combined coagulant activity of microparticles, erythrocytes, and platelets is increased in patients with PV, as evidenced by a significantly reduced clotting time ( P <0.01). 47 …”

Evaluation of platelet aggregation and platelet derived microparticles in acute leukemia patients

“…Circulating PMPs are important procoagulant factors (14,18) and the hypercoagulable state in patients developing thrombotic events could be partially explained by the elevated levels of PMPs.…”

“…PMPs are highly procoagulant due to phosphatidylserine (PS) and tissue factor (TF) expression on their outer membrane, which are the main initiators of the coagulation cascade (12). Elevated levels of PMPs were reported in a wide range of diseases with thrombotic tendency, including cardiovascular diseases and neoplastic diseases (13)(14)(15)(16)(17)(18).…”

Recent Progress in Research on the Pathogenesis of Pulmonary Thromboembolism: An Old Story with New Perspectives

“…The levels of circulating tissue factor bearing MP (TF + MPs) [84] or phosphatidylserine (PS + ) and lactadherin + MPs [85] are higher in patients with a hypercoagulable status than in control subjects. Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with pancreaticobiliary cancers (PBCs) [86].…”