title: Iron and carbon monoxide attenuate degradation of plasmatic coagulation by Crotalus atrox venom.
abstract: Hypofibrinogenemia is an important clinical consequence following envenomation by Crotalus species, usually attenuated or prevented by administration of antivenom. It has been determined that iron and carbon monoxide (CO) enhance fibrinogen as a thrombin substrate, likely secondary to conformational changes in molecular structure. We tested the hypothesis that pretreatment of plasma with iron and CO could attenuate the effects of exposure to Crotalus atrox venom. Human plasma was exposed to 0 to 10 μmol/l ferric chloride (iron source) and 0 to 100 μmol/l CO-releasing molecule-2 (CO source) followed by exposure to 0 to 0.5 μg/ml venom for 5 to 20 min. Changes in coagulation kinetics were determined with thrombelastography. Iron and CO significantly attenuated venom-mediated degradation of plasmatic coagulation in terms of onset time, velocity of clot growth and final clot strength. Further preclinical investigation of iron and CO administration as a 'bridge-to-antivenom' to preserve plasmatic coagulation is justified.
authors.affiliation: aDepartment of Anesthesiology bVIPER Institute, The University of Arizona College of Medicine, Tucson, Arizona, USA.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: Leslie V
authors.initials: LV
authors.lastname: Boyer
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002248:Carbon Monoxide / Q000737:chemistry / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017839:Crotalus / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology*; D063285:Fibrin Clot Lysis Time; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D013916:Thrombelastography
chemical_list: D002712:Chlorides; D003435:Crotalid Venoms; D005290:Ferric Compounds; D005343:Fibrinolytic Agents; D006490:Hemostatics; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D005340:Fibrinogen; C024555:ferric chloride