Published online 8 June 2009
Haematologica, Vol 94, Issue 7, 911-918 doi:10.3324/haematol.13774
Copyright © 2009 by Ferrata Storti Foundation

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Myeloproliferative Neoplasms

Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia

Marijke C. Trappenburg¹, Muriel van Schilfgaarde², Marina Marchetti^3,4, Henri M. Spronk⁴, Hugo ten Cate⁴, Anja Leyte², Wim E. Terpstra¹, Anna Falanga³

¹ Departments of Internal Medicine and
² Clinical Chemistry, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands;
³ Department of Hematology-Oncology, Thrombosis and Hemostasis Center, Ospedali Riuniti di Bergamo, Bergamo, Italy and
⁴ Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands

Correspondence: Anja Leyte, Onze Lieve Vrouwe Gasthuis, Oosterpark 9, 1090, HM Amsterdam, The Netherlands., E-mail:a.leyte{at}olvg.nl

Background: Most cell types, including blood - and vascular cells, produce microparticles upon activation. Since cellular microparticles are known to be elevated in thromboembolic diseases, we hypothesized a role for microparticles in the pathogenesis of thrombosis in essential thrombocythemia.

Design and Methods: In plasma samples from 21 patients with essential thrombocythemia and ten healthy subjects, the levels and the cellular origin of microparticles were determined by flowcytometric analysis, while the microparticle-associated procoagulant activity was measured using a thrombin generation assay.

Results: Patients with essential thrombocythemia had significantly higher numbers of circulating annexin V-positive microparticles than controls (median 4500 vs. 2500x10⁶ events/L; p=0.039), including significantly higher numbers of microparticles positive for the platelet marker CD61 (p=0.043), the endothelial markers CD62E (p=0.009) and CD144 (p=0.021), and for tissue factor (p=0.036). CD62E was co-expressed with the platelet marker CD41 on microparticles, suggesting a bilineage origin of such microparticles, which were observed only in patients with risk factors for thrombosis. Patients with essential thrombocythemia had higher plasma levels of mature von Willebrand factor (p=0.045) but similar propeptide levels compared to controls. In thrombin generation analyses, microparticle-rich plasma from patients with essential thrombocythemia had a shorter lag time (p=0.001) and higher peak height (p=0.038) than plasma from controls. Peak height correlated significantly with the total number of microparticles (R=0.634, p<0.001).

Conclusions: Patients with essential thrombocythemia had higher number of circulating microparticles with platelet and endothelial markers, suggesting ongoing platelet and endothelial activation. This was confirmed by an increased level of mature von Willebrand factor, an abnormal mature von Willebrand factor/propeptide ratio, and a hypercoagulable state reflected in thrombin generation. These findings suggest a role for microparticles in thrombosis in essential thrombocythemia.

Key words: microparticles, essential thrombocythemia, E-selectin, thrombin generation, von Willebrand factor.

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