title: Carbon monoxide releasing molecule-2 attenuates the anticoagulant and amplifies the hypofibrinolytic effects of hypothermia in human plasma in vitro.
abstract: Hypothermia is known to contribute to coagulopathy in trauma and other major surgical procedures. Although the effects of hypothermia on coagulation have been characterized, the effects on fibrinolysis remained to be elucidated. Thus, our goals were to discern the effects of hypothermia on fibrinolysis in human plasma, and secondarily determine if a new procoagulant/antifibrinolytic molecule, carbon monoxide releasing molecule (tricarbonyldichlororuthenium (II) dimer; CORM-2) would modify thrombus growth/disintegration under hypothermic conditions. Normal plasma was exposed to 0 or 100 μmol/l CORM-2, with coagulation activated by tissue factor and fibrinolysis initiated with 100 U/ml tissue-type plasminogen activator. Plasma samples were exposed to 37°, 35°, 33°, 31°, 29°, or 27°C (n = 6 per temperature/CORM-2 concentration). Thrombus growth/disintegration kinetics were monitored with thrombelastography until clot lysis time occurred. Hypothermia significantly prolonged the onset and decreased the velocity of clot growth in plasma without decreasing clot strength. Although hypothermia did not affect the time to onset of fibrinolysis, it did significantly decrease the velocity of lysis. The addition of CORM-2 significantly increased the velocity of clot growth and clot strength at all temperatures tested compared with unexposed plasma. Further, CORM-2 addition significantly prolonged the onset of fibrinolysis and diminished the velocity of lysis. Hypothermia resulted in slower growing, slower lysing thrombi in normal plasma. CORM-2 enhanced coagulation and markedly attenuated fibrinolysis at all temperatures tested. Further investigation is warranted to determine if CORM-2 administration can improve hemostasis in preclinical models of hypothermia and trauma.
authors.affiliation: Department of Anesthesiology, Drexel University College of Medicine, Broad & Vine Streets, Philadelphia, PA 19102, USA. vance.nielsen@drexelmed.edu
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: Shelley J
authors.initials: SJ
authors.lastname: George
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D003029:Coagulants / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007035:Hypothermia / Q000097:blood*; D009942:Organometallic Compounds / Q000494:pharmacology*; D013916:Thrombelastography / Q000187:drug effects
chemical_list: D003029:Coagulants; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer