title: Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes.
abstract: Blood microparticles (MPs) in sickle cell disease (SCD) are reportedly derived only from erythrocytes and platelets. Yet in SCD, endothelial cells and monocytes are activated and abnormally express tissue factor (TF). Thus, sickle blood might contain TF-positive MPs derived from these cells. With the use of flow cytometry to enumerate and characterize MPs, we found total MPs to be elevated in crisis (P =.0001) and steady state (P =.02) in subjects with sickle cell disease versus control subjects. These MPs were derived from erythrocytes, platelets, monocytes, and endothelial cells. Erythrocyte-derived MPs were elevated in sickle crisis (P =.0001) and steady state (P =.02) versus control subjects, as were monocyte-derived MPs (P =.0004 and P =.009, respectively). Endothelial and platelet-derived MPs were elevated in sickle crisis versus control subjects. Total TF-positive MPs were elevated in sickle crisis versus steady state (P =.004) and control subjects (P <.0001) and were derived from both monocytes and endothelial cells. Sickle MPs shortened plasma-clotting time compared with control MPs, and a TF antibody partially inhibited this procoagulant activity. Markers of coagulation were elevated in patients with sickle cell disease versus control subjects and correlated with total MPs and TF-positive MPs (P <.01 for both). These data support the concept that SCD is an inflammatory state with monocyte and endothelial activation and abnormal TF activity.
authors.affiliation: Vascular Biology Center, University of Minnesota Medical School, Minneapolis, USA. shetx001@umn.edu
authors.forename: Arun S
authors.initials: AS
authors.lastname: Shet
authors.forename: Omer
authors.initials: O
authors.lastname: Aras
authors.forename: Kalpna
authors.initials: K
authors.lastname: Gupta
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Hass
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Rausch
authors.forename: Nabil
authors.initials: N
authors.lastname: Saba
authors.forename: Louann
authors.initials: L
authors.lastname: Koopmeiners
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Key
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hebbel
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000378:metabolism / Q000473:pathology*; D017304:Annexin A5 / Q000378:metabolism; D015415:Biomarkers; D001777:Blood Coagulation / Q000502:physiology; D001779:Blood Coagulation Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D010316:Particle Size; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D015415:Biomarkers; D001779:Blood Coagulation Factors; C045071:leukocyte procoagulant activity; D013925:Thromboplastin