title: Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease.
abstract: BACKGROUND
  Sickle cell disease is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and circulating cell-derived microparticles. There is still no consensus on the cellular origin of such microparticles and the exact mechanism by which they may enhance coagulation activation in sickle cell disease.
  
  
  METHODS
  In the present study, we analyzed the origin of circulating microparticles and their procoagulant phenotype during painful crises and steady state in 25 consecutive patients with sickle cell disease.
  
  
  RESULTS
  The majority of microparticles originated from platelets (GPIIIa,CD61) and erythrocytes (glycophorin A,CD235), and their numbers did not differ significantly between crisis and steady state. Erythrocyte-derived microparticles strongly correlated with plasma levels of markers of hemolysis, i.e. hemoglobin (r=-0.58, p<0.001) and lactate dehydrogenase (r=0.59, p<0.001), von Willebrand factor as a marker of platelet/endothelial activation (r=0.44, p<0.001), and D-dimer and prothrombin fragment F1+2 (r=0.52, p<0.001 and r=0.59, p<0.001, respectively) as markers of fibrinolysis and coagulation activation. Thrombin generation depended on the total number of microparticles (r=0.63, p<0.001). Anti-human factor XI inhibited thrombin generation by about 50% (p<0.001), whereas anti-human factor VII was ineffective (p>0.05). The extent of factor XI inhibition was associated with erythrocyte-derived microparticles (r=0.50, p=0.023).
  
  
  CONCLUSIONS
  We conclude that the procoagulant state in sickle cell disease is partially explained by the factor XI-dependent procoagulant properties of circulating erythrocyte-derived microparticles.
authors.affiliation: Department of Haematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: van Beers
authors.forename: Marianne C L
authors.initials: MC
authors.lastname: Schaap
authors.forename: René J
authors.initials: RJ
authors.lastname: Berckmans
authors.forename: Rienk
authors.initials: R
authors.lastname: Nieuwland
authors.forename: Augueste
authors.initials: A
authors.lastname: Sturk
authors.forename: Frederiek F
authors.initials: FF
authors.lastname: van Doormaal
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Biemond
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications; D001777:Blood Coagulation; D055252:Cell-Derived Microparticles / Q000473:pathology*; D004912:Erythrocytes / Q000473:pathology*; D005172:Factor XI; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D005172:Factor XI