title: Carbon monoxide releasing molecule-2 increases the velocity of thrombus growth and strength in hemophilia A, hemophilia B and factor VII-deficient plasmas.
abstract: Carbon monoxide derived from carbon monoxide releasing molecules (CORMs) has been demonstrated to enhance normal plasma thrombus speed of growth and strength in vitro. We tested the hypothesis that tricarbonyldichlororuthenium (II) dimer (CORM-2) improves the velocity of formation and strength of hemophiliac plasma thrombi as determined by thrombelastography. Plasma deficient (<1% normal activity) in factor VIII (FVIII; n = 11 individuals), factor IX (FIX; n = 5 individuals) or factor VII (FVII; n = 4 individuals) was exposed to 0 or 100 micromol CORM-2, with coagulation initiated with tissue factor. Coagulation kinetics were monitored with thrombelastography for 15 min. Paired t-tests were used to analyze FVIII-deficient plasma results; relative change was used to describe the other plasma types tested. In FVIII-deficient plasma, CORM-2 exposure significantly (P < 0.05) increased the velocity of thrombus formation (84%) and strength (48%) compared with plasma not exposed to CORM-2. FXI-deficient clots demonstrated an increase in velocity of formation (63%) and strength (43%) after CORM-2 exposure. Lastly, CORM-2 exposure increased FVII-deficient plasma velocity of formation (45%) and strength (63%). CORM-2 markedly enhanced the velocity of clot growth and strength in hemophiliac plasma. These findings serve as the rationale to determine whether CORMs could be utilized as hemostatic agents.
authors.affiliation: Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA. vgnielsen333@gmail.com
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
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 / Q000097:blood / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005168:Factor VII Deficiency / Q000097:blood*; D006467:Hemophilia A / Q000097:blood; D002836:Hemophilia B / Q000097:blood*; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009942:Organometallic Compounds / Q000494:pharmacology*; D010949:Plasma; D011355:Prodrugs / Q000494:pharmacology*; D013916:Thrombelastography; D013925:Thromboplastin / Q000494:pharmacology
chemical_list: D006490:Hemostatics; D009942:Organometallic Compounds; D011355:Prodrugs; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D013925:Thromboplastin