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Coagulation factor activity patterns of venom-induced consumption coagulopathy in naturally occurring tiger snake (Notechis scutatus) envenomed dogs treated with antivenom.
Toxicon. 2020 Jul 15; 181:36-44.T

Abstract

BACKGROUND

Venom-induced consumption coagulopathy (VICC) from tiger snake (Notechis scutatus) envenomation results in a dose-dependent coagulopathy that is detectable on coagulometry. However, individual coagulation factor activities in dogs with tiger snake envenomation have not been determined. This study aimed to characterise VICC and the time course of recovery in tiger snake envenomed dogs and to investigate an association between tiger snake venom (TSV) concentrations and factor activity.

METHODS

This was a prospective, observational, cohort study. The study cohort was 11 dogs of any age, breed, sex, body weight >10 kg, confirmed serum TSV on ELISA and treated with antivenom. Blood was collected at enrolment before antivenom administration, then at 3, 12 and 24 h after antivenom administration. Tiger snake venom concentrations were detected with a sandwich ELISA. Fibrinogen was measured using a modified Clauss method, and coagulation factors (F) II, V, VII, VIII and X were measured with factor-deficient human plasma using a modified prothrombin (PT) and activated partial thromboplastin (aPTT) method. Linear mixed models, with multiple imputations of censored observations, were used to determine the effect of time and TSV concentration on the coagulation times and factor activity. This cohort was compared to 20 healthy controls.

RESULTS

At enrolment, there were severe deficiencies in fibrinogen, FV and FVIII, with predicted recovery by 10.86, 11.75 and 13.14 h after antivenom, respectively. There were modest deficiencies in FX and FII, with predicted recovery by 20.57 and 32.49 h after antivenom, respectively. No changes were detected in FVII. Prothrombin time and aPTT were markedly prolonged with predicted recovery of aPTT by 12.58 h. Higher serum TSV concentrations were associated with greater deficiencies in FII, FV and FVIII, and greater prolongations in coagulation times. The median (range) serum TSV concentration was 57 (6-2295) ng/mL.

CONCLUSIONS

In tiger snake envenomed dogs, we detected a profound, TSV-concentration-related consumption of select coagulation factors, that rapidly recovered toward normal. These findings allowed further insight into tiger snake VICC in dogs.

Authors+Show Affiliations

Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, 250 Princes Highway, Werribee, VIC, 3030, Australia. Electronic address: louis.eramanis@unimelb.edu.au.Faculty of Veterinary and Agricultural Sciences, University of Melbourne, 250 Princes Highway, Werribee, VIC, 3030, Australia.Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, 250 Princes Highway, Werribee, VIC, 3030, Australia.Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, 250 Princes Highway, Werribee, VIC, 3030, Australia.Australian Venom Research Unit, Department of Pharmacology and Therapeutics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, 3010, Australia. Electronic address: andrew.padula@unimelb.edu.au.Melbourne School of Population and Global Health, University of Melbourne, 207-221 Bouverie St., Parkville, VIC, 3010, Australia. Electronic address: kdw@unimelb.edu.au.Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, 250 Princes Highway, Werribee, VIC, 3030, Australia; Translational Research and Animal Clinical Trial Study Group (TRACTS), Faculty of Veterinary and Agricultural Sciences, University of Melbourne, 250 Princes Highway, Werribee, VIC, 3030, Australia. Electronic address: manuel.boller@unimelb.edu.au.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32330462

Citation

Eramanis, Louis Mark, et al. "Coagulation Factor Activity Patterns of Venom-induced Consumption Coagulopathy in Naturally Occurring Tiger Snake (Notechis Scutatus) Envenomed Dogs Treated With Antivenom." Toxicon : Official Journal of the International Society On Toxinology, vol. 181, 2020, pp. 36-44.
Eramanis LM, Woodward A, Courtman N, et al. Coagulation factor activity patterns of venom-induced consumption coagulopathy in naturally occurring tiger snake (Notechis scutatus) envenomed dogs treated with antivenom. Toxicon. 2020;181:36-44.
Eramanis, L. M., Woodward, A., Courtman, N., Hughes, D., Padula, A., Winkel, K. D., & Boller, M. (2020). Coagulation factor activity patterns of venom-induced consumption coagulopathy in naturally occurring tiger snake (Notechis scutatus) envenomed dogs treated with antivenom. Toxicon : Official Journal of the International Society On Toxinology, 181, 36-44. https://doi.org/10.1016/j.toxicon.2020.03.010
Eramanis LM, et al. Coagulation Factor Activity Patterns of Venom-induced Consumption Coagulopathy in Naturally Occurring Tiger Snake (Notechis Scutatus) Envenomed Dogs Treated With Antivenom. Toxicon. 2020 Jul 15;181:36-44. PubMed PMID: 32330462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coagulation factor activity patterns of venom-induced consumption coagulopathy in naturally occurring tiger snake (Notechis scutatus) envenomed dogs treated with antivenom. AU - Eramanis,Louis Mark, AU - Woodward,Andrew, AU - Courtman,Natalie, AU - Hughes,Dez, AU - Padula,Andrew, AU - Winkel,Kenneth D, AU - Boller,Manuel, Y1 - 2020/04/21/ PY - 2020/01/13/received PY - 2020/03/17/revised PY - 2020/03/31/accepted PY - 2020/4/25/pubmed PY - 2020/7/15/medline PY - 2020/4/25/entrez KW - Canine KW - Clotting factors KW - Notecarin D KW - Prothrombin activator KW - Snake envenomation SP - 36 EP - 44 JF - Toxicon : official journal of the International Society on Toxinology JO - Toxicon VL - 181 N2 - BACKGROUND: Venom-induced consumption coagulopathy (VICC) from tiger snake (Notechis scutatus) envenomation results in a dose-dependent coagulopathy that is detectable on coagulometry. However, individual coagulation factor activities in dogs with tiger snake envenomation have not been determined. This study aimed to characterise VICC and the time course of recovery in tiger snake envenomed dogs and to investigate an association between tiger snake venom (TSV) concentrations and factor activity. METHODS: This was a prospective, observational, cohort study. The study cohort was 11 dogs of any age, breed, sex, body weight >10 kg, confirmed serum TSV on ELISA and treated with antivenom. Blood was collected at enrolment before antivenom administration, then at 3, 12 and 24 h after antivenom administration. Tiger snake venom concentrations were detected with a sandwich ELISA. Fibrinogen was measured using a modified Clauss method, and coagulation factors (F) II, V, VII, VIII and X were measured with factor-deficient human plasma using a modified prothrombin (PT) and activated partial thromboplastin (aPTT) method. Linear mixed models, with multiple imputations of censored observations, were used to determine the effect of time and TSV concentration on the coagulation times and factor activity. This cohort was compared to 20 healthy controls. RESULTS: At enrolment, there were severe deficiencies in fibrinogen, FV and FVIII, with predicted recovery by 10.86, 11.75 and 13.14 h after antivenom, respectively. There were modest deficiencies in FX and FII, with predicted recovery by 20.57 and 32.49 h after antivenom, respectively. No changes were detected in FVII. Prothrombin time and aPTT were markedly prolonged with predicted recovery of aPTT by 12.58 h. Higher serum TSV concentrations were associated with greater deficiencies in FII, FV and FVIII, and greater prolongations in coagulation times. The median (range) serum TSV concentration was 57 (6-2295) ng/mL. CONCLUSIONS: In tiger snake envenomed dogs, we detected a profound, TSV-concentration-related consumption of select coagulation factors, that rapidly recovered toward normal. These findings allowed further insight into tiger snake VICC in dogs. SN - 1879-3150 UR - https://www.unboundmedicine.com/medline/citation/32330462/Coagulation_factor_activity_patterns_of_venom_induced_consumption_coagulopathy_in_naturally_occurring_tiger_snake__Notechis_scutatus__envenomed_dogs_treated_with_antivenom_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-0101(20)30103-3 DB - PRIME DP - Unbound Medicine ER -