title: The procoagulant properties of purified fibrinogen concentrate are enhanced by carbon monoxide releasing molecule-2.
abstract: BACKGROUND
  Fibrinogen concentrate has been demonstrated to enhance coagulation in vitro and in several clinical settings of coagulopathy. We have recently demonstrated that carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances fibrinogen as a substrate for thrombin via an attached heme. The objective of this study was to determine if CORM-2 modified fibrinogen concentrate would enhance coagulation more effectively than CORM-2 naïve fibrinogen concentrate.
  
  
  METHODS
  In the first series of experiments, fibrinogen concentrate (final concentration 300mg/dl) was exposed to 0, 50 or 100μM CORM-2 for 5min at 37°C prior to being added to citrated, fibrinogen depleted plasma. In another series of experiments, citrated plasma obtained from 12 normal subjects was 50% diluted with crystalloid to which was added fibrinogen concentrate (final concentration 300mg/dl) exposed to 0 or 100μM CORM-2. Coagulation was activated with tissue factor (n=8 per condition). Thrombus growth was monitored with thrombelastography for 15min.
  
  
  CONCLUSIONS
  CORM-2 modification of fibrinogen concentrate significantly enhanced the velocity of clot formation (30-50%) and strength (15-31%) in fibrinogen deficient plasma. Similarly, while diluted plasma-derived thrombi demonstrated a marked decrease in velocity of formation (54%) and strength (61%), fibrinogen concentrate significantly enhanced velocity (217%) and strength (171%); however, CORM-2 modified fibrinogen concentrate significantly increased velocity (303%) and strength (205%) to a greater extent. Additional in vitro investigation and in vivo preclinical assessments of the hemostatic efficacy of CORM-2 modified fibrinogen concentrate are warranted.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Machovec
authors.forename: Deepu S
authors.initials: DS
authors.lastname: Ushakumari
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Welsby
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006438:Hemodilution; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000494:pharmacology*; D013916:Thrombelastography / Q000379:methods; D055815:Young Adult
chemical_list: D006490:Hemostatics; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D005340:Fibrinogen