Increased Platelet Turnover and Platelet P-Selectin in Patients with Essential Thrombocythemia and Thrombosis.

Essential thrombocythemia (ET) is a myeloproliferative disorder associated with an increased tendency to thrombosis, the pathogenesis of which is not well known. The aim of the present study was to analyze the relationship between platelet turnover and activation and a history of thrombosis in patients with ET. The expression of platelet P-selectin (measured both in unstimulated platelets and after agonist-stimulation with ADP, thrombin, arachidonic acid (AA), collagen or epinephrine) and the percentage of reticulated platelets (RP) were measured in 53 ET patients with (n=26) or without (n=27) previous thrombosis and in 26 healthy controls. Both variable were assessed using quantitative whole blood cytometry and the results were expressed as percentages and in MESF (molecules of equivalent soluble fluorochrome) units. The results were as follows: 1) patients with thrombosis showed a significantly higher basal platelet P-selectin expression (6.1%, 95% CI: 4.6–6.8) than those without thrombosis (4.6%, 95% CI: 3.7–5.5)) and the healthy controls (3%, 95% CI: 2–4.2) (p= 0.0001 for all comparisons); 2) following thrombin activation, ET patients had a higher mean percentage of platelet P-selectin expression than the controls (61% versus 46%, p = 0.01), but no difference was seen between the two groups of patients; 3) after AA activation, patients with ET and thrombosis also showed higher platelet P-selectin values (78%, 95% CI: 69–86) than those without thrombosis (63%, 95% CI: 55–76) and the controls (46%, 95% CI: 33–58) (p=0.001 for all comparisons); 4) ET patients with thrombosis had a significantly higher mean percentage of RP (18%, 95% CI: 13–20) than patients without thrombosis (13%, 95% CI: 11–18) and the controls (8%, 95% CI: 5–10) (p = 0.0001 for all comparisons). No differences were observed when the patients were separated on the basis of the treatment that they received at the time of study. The above results point at a possible role of AA-induced platelet acitvation in the development of thrombosis in ET and give conceptual support to the prohylactic use of aspirin in such patients.