title: Carbon monoxide-releasing molecule-2 enhances coagulation and diminishes fibrinolytic vulnerability in diluted plasma in vitro.
abstract: BACKGROUND
  A carbon monoxide-releasing molecule (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances coagulation and attenuates vulnerability to fibrinolysis in normal and hemophiliac human plasma. We tested the hypothesis that plasma diluted with resuscitative fluids would demonstrate improved coagulation and decreased fibrinolytic vulnerability after exposure to CORM-2.
  
  
  METHODS
  Normal, platelet-poor plasma was diluted 0%, 20%, 30%, 40%, or 50% with 0.9% NaCl (NS) or low-molecular-weight hydroxyethyl starch (VOL) and, subsequently, exposed to 0 μmol/L or 100 μmol/L CORM-2 before activation with tissue factor (n = 4 per condition). Additional plasma samples diluted with NS or VOL (0% or 30%) were exposed to 0 μmol/L or 100 μmol/L CORM-2 and 0 U/mL or 100 U/mL tissue-type plasminogen activator to assess fibrinolytic vulnerability (n = 8 per condition). Thrombelastographic data were collected until either clot strength stabilized or clot lysis occurred, as appropriate.
  
  
  RESULTS
  CORM-2 exposure maintained normal to supranormal velocity of clot formation and strength in plasma diluted up to 40% with NS. In contrast, although CORM-2 exposure improved coagulation kinetics, dilution with VOL markedly degraded thrombus formation kinetics. Similarly, fibrinolytic vulnerability to tissue-type plasminogen activator was markedly improved by CORM-2 exposure in samples diluted with NS, whereas VOL-diluted thrombi were still abnormally weak and easily lysed compared with undiluted samples despite CORM-2 exposure.
  
  
  CONCLUSIONS
  CORM-2 exposure attenuated the decrease in coagulation kinetics and enhancement of fibrinolytic vulnerability associated with hemodilution. Extensive preclinical investigation remains to be performed to determine the route of administration, safety, and efficacy of CORM-2 and other CORMs to treat trauma-associated bleeding.
authors.affiliation: Department of Anesthesiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA. vance.nielsen@drexelmed.edu
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: Parmis
authors.initials: P
authors.lastname: Green
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Amber
authors.initials: A
authors.lastname: Martin-Ross
authors.forename: Ejaz S
authors.initials: ES
authors.lastname: Khan
authors.forename: James K
authors.initials: JK
authors.lastname: Kirklin
authors.forename: James F
authors.initials: JF
authors.lastname: George
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D003029:Coagulants / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D009942:Organometallic Compounds / Q000494:pharmacology*; D013916:Thrombelastography; D013925:Thromboplastin / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D003029:Coagulants; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator