Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid

ABSTRACT: In Brazil, snakes from the Bothrops genus are responsible for thousands of accidents, and their venoms are mainly composed of proteolytic enzymes. Although the antibothropic serum produced by the Brazilian Institutes is remarkably efficient, more studies are necessary, especially in veteri...

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Main Authors: Warley G. Santos, Rita C.F. Duarte, Claudio R.S. Mattoso, Gabriella M.L. Diamantino, Ana F.M. Botelho, Maria G. Carvalho, Marília M. Melo
Format: Article
Language:English
Published: Colégio Brasileiro de Patologia Animal (CBPA) 2021-04-01
Series:Pesquisa Veterinária Brasileira
Subjects:
Online Access:http://www.scielo.br/pdf/pvb/v41/1678-5150-pvb-41-e06639.pdf
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author Warley G. Santos
Rita C.F. Duarte
Claudio R.S. Mattoso
Gabriella M.L. Diamantino
Ana F.M. Botelho
Maria G. Carvalho
Marília M. Melo
author_facet Warley G. Santos
Rita C.F. Duarte
Claudio R.S. Mattoso
Gabriella M.L. Diamantino
Ana F.M. Botelho
Maria G. Carvalho
Marília M. Melo
author_sort Warley G. Santos
collection DOAJ
description ABSTRACT: In Brazil, snakes from the Bothrops genus are responsible for thousands of accidents, and their venoms are mainly composed of proteolytic enzymes. Although the antibothropic serum produced by the Brazilian Institutes is remarkably efficient, more studies are necessary, especially in veterinary medicine. The venom contain enzymes and non-enzymatic proteins that interfere with hemostasis leading to hemorrhage or even thrombosis. Possible treatment associations with known bothropic antivenom were the reason for the development of the present study. The aim of this study was to evaluate hemostasis alterations caused by Bothrops alternatus venom in rabbits followed by treatments with anti-bothropic serum, tranexamic acid and desmopressin. Twenty New Zealand rabbits were distributed into five groups (n=4) that were experimentally envenomed with 150mcg/kg of B. alternatus venom via intramuscular injection and treated as follow: Group 1 (G1) was the positive control and received venom and PBS/BSA; Group 2 (G2) was treated with tranexamic acid; Group 3 (G3) with desmopressin; Group 4 (G4) with tranexamic acid and anti-bothropic serum; and Group 5 (G5) with anti-bothropic serum and desmopressin. Blood samples were collected before venom administration, and one, four, eight and 12 hours after, for Partial activated partial thromboplastin time, Prothrombin Time, Thrombin Time and fibrinogen evaluation. Thrombin generation (TG) test was carried out with a pool of samples from final times (8 and 12h). At the end of 12h, all animals were euthanized and necropsy was conducted. Samples from muscle tissue, heart, lungs and kidney were analyzed. Classic coagulation tests showed no significant differences amongst groups and times. However, TG indicated that the venom causes a hypocoagulability state, which was not reversed by proposed treatments. Histology showed muscle inflammation, hemorrhage and necrosis, as well as hemorrhage in other tissues with no differences amongst groups. B. alternatus envenomation causes hypocoagulability detected by TG assay, but not through classical coagulation tests. The use of tranexamic acid and desmopressin for hemostasis stabilization after inoculation of the venom did not show advantage in coagulation restoration.
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spelling doaj.art-c118bdd1bee444aab4cee10d1139b8382022-12-22T04:09:46ZengColégio Brasileiro de Patologia Animal (CBPA)Pesquisa Veterinária Brasileira1678-51502021-04-014110.1590/1678-5150-pvb-6639Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acidWarley G. SantosRita C.F. DuarteClaudio R.S. MattosoGabriella M.L. DiamantinoAna F.M. Botelhohttps://orcid.org/0000-0001-5204-0512Maria G. CarvalhoMarília M. Melohttps://orcid.org/0000-0003-3630-6776ABSTRACT: In Brazil, snakes from the Bothrops genus are responsible for thousands of accidents, and their venoms are mainly composed of proteolytic enzymes. Although the antibothropic serum produced by the Brazilian Institutes is remarkably efficient, more studies are necessary, especially in veterinary medicine. The venom contain enzymes and non-enzymatic proteins that interfere with hemostasis leading to hemorrhage or even thrombosis. Possible treatment associations with known bothropic antivenom were the reason for the development of the present study. The aim of this study was to evaluate hemostasis alterations caused by Bothrops alternatus venom in rabbits followed by treatments with anti-bothropic serum, tranexamic acid and desmopressin. Twenty New Zealand rabbits were distributed into five groups (n=4) that were experimentally envenomed with 150mcg/kg of B. alternatus venom via intramuscular injection and treated as follow: Group 1 (G1) was the positive control and received venom and PBS/BSA; Group 2 (G2) was treated with tranexamic acid; Group 3 (G3) with desmopressin; Group 4 (G4) with tranexamic acid and anti-bothropic serum; and Group 5 (G5) with anti-bothropic serum and desmopressin. Blood samples were collected before venom administration, and one, four, eight and 12 hours after, for Partial activated partial thromboplastin time, Prothrombin Time, Thrombin Time and fibrinogen evaluation. Thrombin generation (TG) test was carried out with a pool of samples from final times (8 and 12h). At the end of 12h, all animals were euthanized and necropsy was conducted. Samples from muscle tissue, heart, lungs and kidney were analyzed. Classic coagulation tests showed no significant differences amongst groups and times. However, TG indicated that the venom causes a hypocoagulability state, which was not reversed by proposed treatments. Histology showed muscle inflammation, hemorrhage and necrosis, as well as hemorrhage in other tissues with no differences amongst groups. B. alternatus envenomation causes hypocoagulability detected by TG assay, but not through classical coagulation tests. The use of tranexamic acid and desmopressin for hemostasis stabilization after inoculation of the venom did not show advantage in coagulation restoration.http://www.scielo.br/pdf/pvb/v41/1678-5150-pvb-41-e06639.pdfHemostasisrabbitsBothrops alternatusanti-bothropic serumdesmopressintranexamin acidcoagulationViperidae envenomationthrombin generation
spellingShingle Warley G. Santos
Rita C.F. Duarte
Claudio R.S. Mattoso
Gabriella M.L. Diamantino
Ana F.M. Botelho
Maria G. Carvalho
Marília M. Melo
Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid
Pesquisa Veterinária Brasileira
Hemostasis
rabbits
Bothrops alternatus
anti-bothropic serum
desmopressin
tranexamin acid
coagulation
Viperidae envenomation
thrombin generation
title Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid
title_full Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid
title_fullStr Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid
title_full_unstemmed Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid
title_short Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid
title_sort hemostatic evaluation of rabbits envenomed with bothrops alternatus treated with anti bothropic serum desmopressin and tranexamin acid
topic Hemostasis
rabbits
Bothrops alternatus
anti-bothropic serum
desmopressin
tranexamin acid
coagulation
Viperidae envenomation
thrombin generation
url http://www.scielo.br/pdf/pvb/v41/1678-5150-pvb-41-e06639.pdf
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