title: Carbon monoxide releasing molecule-2 enhances coagulation and diminishes fibrinolytic vulnerability in subjects exposed to warfarin.
abstract: BACKGROUND
  It has been recently demonstrated that 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 obtained from warfarin-treated subjects would demonstrate improved coagulation and decreased fibrinolytic vulnerability following exposure to CORM-2.
  
  
  METHODS
  Anonymous donor plasma samples with international normalized ratios (INR) values ranging from 1.5-5.4 were exposed to 0 or 100 microM CORM-2 and activated with tissue factor (12 samples). Additional samples within the same INR range were exposed to 0 or 100 microM CORM-2 and 0 or 100 U/ml tissue-type plasminogen activator (tPA) to assess fibrinolytic vulnerability (8 samples). Thrombelastographic data were collected until either clot strength stabilized or clot lysis occurred as appropriate.
  
  
  CONCLUSIONS
  In the absence of tPA, all but one sample (INR=1.5) demonstrated a marked increase in the velocity of clot formation (40-577%) and strength (42-180%) following CORM-2 exposure. Of interest, in the presence of tPA, all samples (including the previously unresponsive sample) were noted to have an increase in the velocity of clot formation and strength, coupled with a prolonged onset to maximal rate of clot lysis (60-242%) and increased clot lysis time (74-149%). As with normal and hemophilic plasma, both enhancement of coagulation and attenuation of fibrinolysis occur following CORM-2 exposure in plasma from warfarin-treated subjects. Future investigation must determine if carbon monoxide releasing molecules could be used therapeutically to control bleeding in warfarin-treated patients.
authors.affiliation: Department of Anesthesiology, Drexel University College of Medicine, and Hahnemann University Hospital, Philadelphia, PA 19102, USA. vance.nielsen@drexelmed.edu
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
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*; D002248:Carbon Monoxide / Q000494:pharmacology*; D005342:Fibrinolysis; D006470:Hemorrhage; D006801:Humans; D019934:International Normalized Ratio; D009942:Organometallic Compounds; D010949:Plasma; D010960:Plasminogen Activators; D013916:Thrombelastography; D013925:Thromboplastin; D013927:Thrombosis; D010959:Tissue Plasminogen Activator; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D014859:Warfarin; D002248:Carbon Monoxide; D013925:Thromboplastin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator