Iron and carbon monoxide attenuate degradation of plasmatic coagulation by Crotalus atrox venom

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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.

Original languageEnglish (US)
JournalBlood Coagulation and Fibrinolysis
DOIs
StateAccepted/In press - Nov 7 2015

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Crotalus
Venoms
Carbon Monoxide
Iron
Antivenins
Thrombelastography
Molecular Structure
Thrombin
Fibrinogen
Growth

ASJC Scopus subject areas

  • Hematology

Cite this

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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.",
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AU - Boyer, Leslie V

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AB - 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.

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