Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom

Olver, Christine S.; Nielsen, Vance G.

doi:10.1007/s10534-017-0035-9

Cited by 3 publications

(1 citation statement)

References 11 publications

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“…Using the representative measurement of TTG, dog plasma, with a mean of 108.5 dynes/cm 2 , is hypocoagulable compared with almost all species tested (horse, 313 dcs; pig, 230 dcs; human being, 168 dcs; rabbit, 232 dcs; and rat, 188 dcs) in previous reports . The same is true for the rate of clotting.…”

Section: Discussionmentioning

confidence: 58%

Carbon Monoxide‐Releasing Molecule Enhances Coagulation and Decreases Fibrinolysis in Normal Canine Plasma

Donaghy

Yoo²,

Johnson

et al. 2018

Basic Clin Pharma Tox

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The dog is an important companion animal and also purpose-bred for research studies. Coagulopathies in dogs are common, although the availability of blood products for therapy is inconsistent throughout the profession. A pro-coagulant therapeutic that is readily available and easily stored would be useful for the treatment of coagulopathies. Tricarbonyldichlororuthenium (II) dimer [Carbon monoxide-releasing molecule-2 (CORM-2)] acts as a prothrombotic agent in plasma by increasing the velocity of clot formation and clot strength, and by decreasing the clot's vulnerability to fibrinolysis. We sought to test CORM-2's effect on coagulation and fibrinolysis in vitro in canine plasma using thromboelastography. Measures of the rate of clot formation and clot strength in plasma without CORM-2 were highly correlated with fibrinogen concentration. We found that CORM-2 significantly enhanced the rate of clot formation and clot strength and significantly reduced the rate of fibrinolysis and the clot lysis time. The per cent change in rate of clot formation and clot strength was not significantly correlated with fibrinogen concentration, indicating that CORM-2's pro-coagulant effect is not dependent on fibrinogen concentration. This study corroborates studies in other species that show that CORM-2 is pro-coagulant in plasma, and lays the groundwork for developing CORM-2 as a therapeutic agent for canine coagulopathies. Future studies will evaluate the effect of CORM-2 on whole blood both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 58%

Carbon Monoxide‐Releasing Molecule Enhances Coagulation and Decreases Fibrinolysis in Normal Canine Plasma

Donaghy

Yoo²,

Johnson

et al. 2018

Basic Clin Pharma Tox

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Effects of purified human fibrinogen modified with carbon monoxide and iron on coagulation in rabbits injected with Crotalus atrox venom

Nielsen

2017

J Thromb Thrombolysis

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While snake venom derived enzymes, such as the thrombin-like activity possessing ancrod, have been used to treat thrombotic disease by defibrinogenating patients, the therapeutic potential of fibrinogenolytic snake venom enzymes, such as those derived from Crotalus atrox, have not been fully explored. However, one of the potential risks of administering fibrinogenolytic enzymes to effect defibrinogenation is hemorrhage secondary to hypofibrinogenemia. The present investigation sought to determine if human fibrinogen modified with carbon monoxide (CO) and iron (Fe) could resist degradation by C. atrox venom as has been seen in vitro in a recently developed rabbit model of envenomation. Compared with unmodified human fibrinogen, CO/Fe modified fibrinogen administered prior to envenomation had significantly shorter onset of coagulation and greater strength; however, when administered after envenomation, there was no differences between the two types of fibrinogen. Of interest, when administered after envenomation, both types of fibrinogen delayed the onset of coagulation while increasing plasma clot strength, a mixed effect likely secondary to formation of fibrinogen degradation products. Further preclinical investigations are needed to further define the benefits and risks of the use of fibrinogenolytic enzymes as defibrinogenating agents, as well as the risks of the "biochemical brakes" used to modulate the activity or substrate of the fibrinogenolytic enzyme.

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Snakebite: An Exploratory Cost-Effectiveness Analysis of Adjunct Treatment Strategies

Herzel

Samuel

Bulfone

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Abstract.The cost-effectiveness of the standard of care for snakebite treatment, antivenom, and supportive care has been established in various settings. In this study, based on data from South Indian private health-care providers, we address an additional question: “For what cost and effectiveness values would adding adjunct-based treatment strategies to the standard of care for venomous snakebites be cost-effective?” We modeled the cost and performance of potential interventions (e.g., pharmacologic or preventive) used adjunctively with antivenom and supportive care for the treatment of snakebite. Because these potential interventions are theoretical, we used a threshold cost-effectiveness approach to explore this forward-looking concept. We examined economic parameters at which these interventions could be cost-effective or even cost saving. A threshold analysis was used to examine the addition of new interventions to the standard of care. Incremental cost-effectiveness ratios were used to compare treatment strategies. One-way, scenario, and probabilistic sensitivity analyses were conducted to analyze parameter uncertainty and define cost and effectiveness thresholds. Our results suggest that even a 3% reduction in severe cases due to an adjunct strategy is likely to reduce the cost of overall treatment and have the greatest impact on cost-effectiveness. In this model, for example, an investment of $10 of intervention that reduces the incidence of severe cases by 3%, even without changing antivenom usage patterns, creates cost savings of $75 per individual. These findings illustrate the striking degree to which an adjunct intervention could improve patient outcomes and be cost-effective or even cost saving.

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Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom

Cited by 3 publications

References 11 publications

Carbon Monoxide‐Releasing Molecule Enhances Coagulation and Decreases Fibrinolysis in Normal Canine Plasma

Carbon Monoxide‐Releasing Molecule Enhances Coagulation and Decreases Fibrinolysis in Normal Canine Plasma

Effects of purified human fibrinogen modified with carbon monoxide and iron on coagulation in rabbits injected with Crotalus atrox venom

Snakebite: An Exploratory Cost-Effectiveness Analysis of Adjunct Treatment Strategies

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