title: Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia.
abstract: 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.
  
  
  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. 2500x10(6) 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.
authors.affiliation: Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Marijke C
authors.initials: MC
authors.lastname: Trappenburg
authors.forename: Muriel
authors.initials: M
authors.lastname: van Schilfgaarde
authors.forename: Marina
authors.initials: M
authors.lastname: Marchetti
authors.forename: Henri M
authors.initials: HM
authors.lastname: Spronk
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Anja
authors.initials: A
authors.lastname: Leyte
authors.forename: Wim E
authors.initials: WE
authors.lastname: Terpstra
authors.forename: Anna
authors.initials: A
authors.lastname: Falanga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D003029:Coagulants / Q000378:metabolism*; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000175:diagnosis; D013927:Thrombosis; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D003029:Coagulants; D019040:E-Selectin; D005819:Genetic Markers; D014841:von Willebrand Factor; D013917:Thrombin