Essential thrombocythaemia (ET) is a clonal myeloproliferative disorder associated with an increased risk of both thromboembolic and bleeding complications. Platelet activation plays a crucial role in the pathogenesis of prethrombotic conditions. The platelet surface expression of p-selectin (CD62p) and thrombospondin (TSP) has been shown to correlate with platelet activation. In the present study, we used a flow cytometric assay to study whether the fraction of platelets expressing CD62p and TSP is increased in newly diagnosed ET. Thirty-four patients with newly diagnosed ET and 25 healthy control subjects were investigated. The proportion of platelets expressing the activation-dependent antigens CD62p and TSP was higher in patients with ET (CD62p: 14.7+/-15.0%; TSP: 12.4+/-9.9%) as compared with healthy control subjects (CD62p: 3.0+/-4.0%; TSP: 3.2+/-3.2%; p< 0.001). In ET, there was a linear correlation between platelet surface expression of CD62p and TSP (p<0.0001, r=0.83). At diagnosis of ET, 20 patients were symptomatic and 14 asymptomatic. Compared with asymptomatic ET patients there was no difference in the expression of CD62p (18.3+/-16.2% vs. 14.5+/-13.4%) and TSP (14.4+/-9.8% vs. 12.8+/-9.5%) in symptomatic ET patients. In conclusion, increased expression of platelet neoantigens is present at the diagnosis of ET. Both activation-dependent epitopes CD62p and TSP are increasingly expressed on the platelet surface in newly diagnosed ET patients.