title: Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation.
abstract: BACKGROUND
  Red blood cell-derived microparticles (RMPs) are small phospholipid vesicles shed from RBCs in blood units, where they accumulate during storage. Because microparticles are bioactive, it could be suggested that RMPs are mediators of posttransfusion complications or, on the contrary, constitute a potential hemostatic agent.
  
  
  METHODS
  This study was performed to establish the impact on coagulation of RMPs isolated from blood units. Using calibrated automated thrombography, we investigated whether RMPs affect thrombin generation (TG) in plasma.
  
  
  RESULTS
  We found that RMPs were not only able to increase TG in plasma in the presence of a low exogenous tissue factor (TF) concentration, but also to initiate TG in plasma in absence of exogenous TF. TG induced by RMPs in the absence of exogenous TF was neither affected by the presence of blocking anti-TF nor by the absence of Factor (F)VII. It was significantly reduced in plasma deficient in FVIII or F IX and abolished in FII-, FV-, FX-, or FXI-deficient plasma. TG was also totally abolished when anti-XI 01A6 was added in the sample. Finally, neither Western blotting, flow cytometry, nor immunogold labeling allowed the detection of traces of TF antigen. In addition, RMPs did not comprise polyphosphate, an important modulator of coagulation.
  
  
  CONCLUSIONS
  Taken together, our data show that RMPs have FXI-dependent procoagulant properties and are able to initiate and propagate TG. The anionic surface of RMPs might be the site of FXI-mediated TG amplification and intrinsic tenase and prothrombinase complex assembly.
authors.affiliation: Service Régional Vaudois de Transfusion Sanguine, Epalinges, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rubin
authors.forename: Julien
authors.initials: J
authors.lastname: Delobel
authors.forename: Michel
authors.initials: M
authors.lastname: Prudent
authors.forename: Niels
authors.initials: N
authors.lastname: Lion
authors.forename: Kid
authors.initials: K
authors.lastname: Kohl
authors.forename: Erik I
authors.initials: EI
authors.lastname: Tucker
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Tissot
authors.forename: Anne
authors.initials: A
authors.lastname: Angelillo-Scherrer
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001780:Blood Coagulation Tests; D001793:Blood Preservation; D015153:Blotting, Western; D055252:Cell-Derived Microparticles / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism*; D005172:Factor XI / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D010949:Plasma / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005172:Factor XI; D013925:Thromboplastin; D013917:Thrombin