Markers of Endothelial and In Vivo Platelet Activation in Patients with Essential Thrombocythemia and Polycythemia Vera

Abstract

We investigated endothelial and in vivo platelet activation in a cohort of 52 patients with essential thrombocythemia (ET) and polycythemia vera (PV) before and after cytoreductive treatment, 22 healthy controls, and 17 patients with acute cerebrovascular ischemia (ACVI) and normal platelet counts. We measured platelet expression of CD62P and CD63 antigens and levels of soluble vascular cell adhesion molecule 1 (sVCAM-1). We found increased in vivo platelet activation in all patients with ET and PV, both before and after cytoreductive treatment, compared with controls. In patients with arterial thrombosis, platelet expression of CD62P, and in patients with erythromelalgia, expression of both markers was higher compared with expression in patients without thrombotic complications. In patients with ET and PV before and after treatment, sVCAM-1 expression was increased compared with expression in controls but also compared with expression in patients with ACVI and normal platelet counts. In patients with arterial thrombosis and erythromelalgia, in vivo platelet activation correlated with the level of sVCAM-1. Our findings indicated that in vivo platelet activation reflects intrinsic platelet defects in patients with ET and PV, persists after cytoreductive treatment, and results in endothelial damage, probably through release of angiogenic factors and/or activation of white blood cells.

JAK2V 617 F-positive endothelial cells contribute to clotting abnormalities in myeloproliferative neoplasms

“…In our model, ECs are, at least in part, responsible for dysfunctional hemostasis in response to injury, opposing some previous reports suggesting that JAK2V 617 F + ECs may be prothrombotic (35). One potential explanation for these differences is the remarkable heterogeneity of ECs.…”

The Role of JAK2 V617F Mutation, Spontaneous Erythropoiesis and Megakaryocytopoiesis, Hypersensitive Platelets, Activated Leukocytes, and Endothelial Cells in the Etiology of Thrombotic Manifestations in Polycythemia Vera and Essential Thrombocythemia

“…This was more marked in patients with arterial thrombosis or erythromelalgia. 107 This platelet activation was associated with an increase in plasma sVCAM-1, suggesting an endothelial cell activation, which again was more marked in patients with previous arterial thromboses or erythromelalgia.…”

“…Other studies also showed the persistence of platelet activation with endothelial cell activation after cytoreductive therapy. 106,107 These data may account for the persistent risk of thromboses, even if it is decreased, in patients treated with hydroxyurea, as shown by several retrospective studies and a prospective controlled clinical trial. 132 We also noticed an increase in the platelet volume, which very likely is linked to enlarged, mature MKs in ET/PV.…”

Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?

“…We now aimed at investigating the effect of exposure of PMN to P‐selectin in vivo . For this purpose we studied the PMN of patients with myeloproliferative disease (MPD), who reportedly have exposed P‐selectin on platelet surfaces [2–5]. Platelet‐mediated up‐regulation of TF on PMN could have clinical relevance, in view of the increased thrombotic risk in MPD [6–9].…”