Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid / Avaliação hemostática de coelhos envenenados com Bothrops alternatus e tratados com soro antibotrópico, desmopressina e ácido tranexâmico

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.(AU)

No Brasil, as serpentes do gênero Bothrops são responsáveis por milhares de acidentes, e seus venenos são compostos principalmente de enzimas proteolíticas. Embora o soro antiofídico produzido pelos institutos brasileiros seja notavelmente eficiente, mais estudos são necessários, especialmente na medicina veterinária. O veneno contem enzimas e proteínas não-enzimáticas que interferem com a hemostasia levando a hemorragias ou trombose. A associação de outros tratamentos ao soro antibotrópico foi a razão para o desenvolvimento do presente estudo. O objetivo deste estudo foi avaliar as alterações da hemostasia causadas pelo veneno de Bothrops alternatus em coelhos, após tratamento com soro antibotrópico, ácido tranexâmico e desmopressina. Vinte coelhos da Nova Zelândia foram distribuídos em cinco grupos (n = 4) que foram submetidos a experimentos com 150mcg/kg de veneno de B. alternatus por injeção intramuscular. O Grupo 1 (G1) foi o controle positivo e recebeu veneno e PBS / BSA, enquanto o Grupo 2 (G2) foi tratado com ácido tranexâmico, o Grupo 3 (G3) com desmopressina, o Grupo 4 (G4) com ácido tranexâmico e soro antibotrópico, e o Grupo 5 (G5) com soro antibotrópico e desmopressina. As amostras de sangue foram coletadas antes da administração do veneno, e uma, quatro, oito e 12 horas após os tratamentos para realização de tempo de tromboplastina parcial ativada parcial (TTPa), tempo de protrombina (TP), tempo de trombina (TT) e mensuração de fibrinogênio. Para o ensaio de geração de trombina (TG) foi realizado com um pool de amostras nos tempos finais (8 e 12h). Ao final das 12h, todos os animais foram sacrificados e a necropsia foi realizada. Amostras de tecido muscular, coração, pulmões e rins foram analisadas. Os testes TTPa, TP, TT e fibrinogênio não mostraram diferenças significativas entre os grupos e os tempos. No entanto, o TG indicou que o veneno causa um estado de hipocoagulabilidade, que não foi revertido pelos tratamentos propostos. Na histologia, foram observadas inflamação muscular, hemorragia e necrose, além de hemorragia em outros tecidos, sem diferenças entre os grupos. O envenenamento por B. alternatus causa hipocoagulabilidade detectada mais precocemente pelo teste de geração de trombina. O uso de ácido tranexâmico e desmopressina para estabilização da hemostasia após a inoculação do veneno não mostrou vantagem na restauração da coagulação.(AU)

Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid / Avaliação hemostática de coelhos envenenados com Bothrops alternatus e tratados com soro antibotrópico, desmopressina e ácido tranexâmico

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.(AU)

No Brasil, as serpentes do gênero Bothrops são responsáveis por milhares de acidentes, e seus venenos são compostos principalmente de enzimas proteolíticas. Embora o soro antiofídico produzido pelos institutos brasileiros seja notavelmente eficiente, mais estudos são necessários, especialmente na medicina veterinária. O veneno contem enzimas e proteínas não-enzimáticas que interferem com a hemostasia levando a hemorragias ou trombose. A associação de outros tratamentos ao soro antibotrópico foi a razão para o desenvolvimento do presente estudo. O objetivo deste estudo foi avaliar as alterações da hemostasia causadas pelo veneno de Bothrops alternatus em coelhos, após tratamento com soro antibotrópico, ácido tranexâmico e desmopressina. Vinte coelhos da Nova Zelândia foram distribuídos em cinco grupos (n = 4) que foram submetidos a experimentos com 150mcg/kg de veneno de B. alternatus por injeção intramuscular. O Grupo 1 (G1) foi o controle positivo e recebeu veneno e PBS / BSA, enquanto o Grupo 2 (G2) foi tratado com ácido tranexâmico, o Grupo 3 (G3) com desmopressina, o Grupo 4 (G4) com ácido tranexâmico e soro antibotrópico, e o Grupo 5 (G5) com soro antibotrópico e desmopressina. As amostras de sangue foram coletadas antes da administração do veneno, e uma, quatro, oito e 12 horas após os tratamentos para realização de tempo de tromboplastina parcial ativada parcial (TTPa), tempo de protrombina (TP), tempo de trombina (TT) e mensuração de fibrinogênio. Para o ensaio de geração de trombina (TG) foi realizado com um pool de amostras nos tempos finais (8 e 12h). Ao final das 12h, todos os animais foram sacrificados e a necropsia foi realizada. Amostras de tecido muscular, coração, pulmões e rins foram analisadas. Os testes TTPa, TP, TT e fibrinogênio não mostraram diferenças significativas entre os grupos e os tempos. No entanto, o TG indicou que o veneno causa um estado de hipocoagulabilidade, que não foi revertido pelos tratamentos propostos. Na histologia, foram observadas inflamação muscular, hemorragia e necrose, além de hemorragia em outros tecidos, sem diferenças entre os grupos. O envenenamento por B. alternatus causa hipocoagulabilidade detectada mais precocemente pelo teste de geração de trombina. O uso de ácido tranexâmico e desmopressina para estabilização da hemostasia após a inoculação do veneno não mostrou vantagem na restauração da coagulação.(AU)

Diabetes insipidus central em felino jovem / Central diabetes insipidus in a young feline

Background: Central diabetes insipidus (CDI) is an endocrine disorder caused by the failure to produce, transport, orrelease ADH. This disease may show a primary etiology (idiopathic or congenital) or a secondary one (trauma or neoplasms). It is characterized by signs such as polyuria and polydipsia. The definitive diagnosis is obtained by the two-stepwater deprivation test; the absence of adequate urinary concentration in the first stage confirms the diagnosis of diabetesinsipidus and, in the second stage, the response to the application of synthetic desmopressin confirms a central origin.Because CDI is rare in felines, the aim of this study was to report the occurrence of a case of CDI, probably of congenitalprimary origin, in an 8-month-old kitten.Case: An 8-month-old male feline, castrated, 3.2 kg, was brought to consultation with a report of polydipsia, polyuria,smaller size and weight, and lower activity when compared to his brother, for several months. On physical examination,lethargy, body score 2/5, and mild dehydration were noted, as well as deciduous teeth that should have already been replaced. Abdominal ultrasound and laboratory tests were requested, which ruled out chronic kidney disease (CKD), diabetesmellitus (DM), hyperadrenocorticism (HAC), and hyperthyroidism. Due to the fact that urinalysis evidenced hyposthenuria(urinary density [UD] 1.004), CDI was suspected. The patient underwent a water deprivation test and, after 7.5 h, lost4.7% of his initial weight, while UD was 1.012, confirming the diagnosis of DI. The investigation then proceeded to theevaluation of the response to synthetic desmopressin by the application of 5 U IM. Two h later, UD was 1.019, confirming...

Diabetes insipidus central em felino jovem / Central diabetes insipidus in a young feline

Background: Central diabetes insipidus (CDI) is an endocrine disorder caused by the failure to produce, transport, orrelease ADH. This disease may show a primary etiology (idiopathic or congenital) or a secondary one (trauma or neoplasms). It is characterized by signs such as polyuria and polydipsia. The definitive diagnosis is obtained by the two-stepwater deprivation test; the absence of adequate urinary concentration in the first stage confirms the diagnosis of diabetesinsipidus and, in the second stage, the response to the application of synthetic desmopressin confirms a central origin.Because CDI is rare in felines, the aim of this study was to report the occurrence of a case of CDI, probably of congenitalprimary origin, in an 8-month-old kitten.Case: An 8-month-old male feline, castrated, 3.2 kg, was brought to consultation with a report of polydipsia, polyuria,smaller size and weight, and lower activity when compared to his brother, for several months. On physical examination,lethargy, body score 2/5, and mild dehydration were noted, as well as deciduous teeth that should have already been replaced. Abdominal ultrasound and laboratory tests were requested, which ruled out chronic kidney disease (CKD), diabetesmellitus (DM), hyperadrenocorticism (HAC), and hyperthyroidism. Due to the fact that urinalysis evidenced hyposthenuria(urinary density [UD] 1.004), CDI was suspected. The patient underwent a water deprivation test and, after 7.5 h, lost4.7% of his initial weight, while UD was 1.012, confirming the diagnosis of DI. The investigation then proceeded to theevaluation of the response to synthetic desmopressin by the application of 5 U IM. Two h later, UD was 1.019, confirming...(AU)

Central Diabetes insipidus in a cat

Background: Diabetes insipidus is a rare disease in cats with few reports in the scientifi c literature. It has two major forms: Central Diabetes Insipidus (CDI); characterized by decreased secretion of antidiuretic hormone (ADH), and Nephrogenic Diabetes Insipidus (NDI); characterized by decreased ability to concentrate urine because of resistance to ADH. The diagnosis is based on excluding diseases with polydipsia/polyuria, the water deprivation test and response to desmopressin. This case report describes Central Diabetes Insipidus in a domestic cat, as well as its response to desmopressin administered intranasally. Case: A 2-year old, male cat of non-defi ned breed and castrated was seen due to a history of polyuria and polydipsia (PU/ PD) that arose after allegedly ingesting thorns that got stuck to its body while going out of the house. Physical examination revealed an active well-fed animal with mild dehydration and persistent paradoxical ischuria. The complementary tests performed: abdominal ultrasound, blood test, urinalysis, serum urea, creatinine, glucose, cortisol, total T4, Total T3 and vasopressin, were within the reference values, except for urinary density and T4 that were below the standard. Based on the laboratory results, conditions compatible with PU and PD symptoms were excluded; however, despite normal vasopressin levels, diabetes insipidus was not ruled...(AU)

Central Diabetes insipidus in a cat

Background: Diabetes insipidus is a rare disease in cats with few reports in the scientifi c literature. It has two major forms: Central Diabetes Insipidus (CDI); characterized by decreased secretion of antidiuretic hormone (ADH), and Nephrogenic Diabetes Insipidus (NDI); characterized by decreased ability to concentrate urine because of resistance to ADH. The diagnosis is based on excluding diseases with polydipsia/polyuria, the water deprivation test and response to desmopressin. This case report describes Central Diabetes Insipidus in a domestic cat, as well as its response to desmopressin administered intranasally. Case: A 2-year old, male cat of non-defi ned breed and castrated was seen due to a history of polyuria and polydipsia (PU/ PD) that arose after allegedly ingesting thorns that got stuck to its body while going out of the house. Physical examination revealed an active well-fed animal with mild dehydration and persistent paradoxical ischuria. The complementary tests performed: abdominal ultrasound, blood test, urinalysis, serum urea, creatinine, glucose, cortisol, total T4, Total T3 and vasopressin, were within the reference values, except for urinary density and T4 that were below the standard. Based on the laboratory results, conditions compatible with PU and PD symptoms were excluded; however, despite normal vasopressin levels, diabetes insipidus was not ruled...

Diabetes insípido em um cão

Background: Diabetes insipidus (DI) is a rare endocrine disorder in dogs altering the mechanism of retention and excretion of water, with concomitant polyuria and polydipsia (PU/PD), and low urine specifi c gravity. The water deprivation test followed by response to application of desmopressin is the diagnostic test for the disease. However, the literature is still scarce about laboratorial and clinical aspects of DI in small animals. Thus, the aim of this study is to report a case of DI in a canine, emphasizing its diagnosis through the water deprivation test.Case: A male mongrel dog, 5 years-old, not neutered, 13kg of body weight, was presented with intense PU/PD (500mL/kg/day of water consumption). Physical examination showed normal routine clinical parameters. Additional tests were asked (abdominal ultrasound, blood count, serum biochemical (creatinine, alanine aminotransferase (ALT), total cholesterol, alkaline phosphatase (ALP) and glucose) and dexamethasone suppression test), but they showed no signifi cant changes. Thus, it was suspected that the animal had an uncommon endocrinopathy, DI. For its confi rmation, it was made the water deprivation test with application of desmopressin acetate. The patient remained without access to water and without fluidtherapy with urethral sounding and bladder emptying. The measurement of urinary gravity and volume were made every hour

Diabetes insípido em um cão / Diabetes Insipidus in a Dog

Background: Diabetes insipidus (DI) is a rare endocrine disorder in dogs altering the mechanism of retention and excretion of water, with concomitant polyuria and polydipsia (PU/PD), and low urine specific gravity. The water deprivation test followed by response to application of desmopressin is the diagnostic test for the disease. However, the literature is still scarce about laboratorial and clinical aspects of DI in small animals. Thus, the aim of this study is to report a case of DI in a canine, emphasizing its diagnosis through the water deprivation test. Case: A male mongrel dog, 5 years-old, not neutered, 13kg of body weight, was presented with intense PU/PD (500mL/kg/day of water consumption). Physical examination showed normal routine clinical parameters. Additional tests were asked (abdominal ultrasound, blood count, serum biochemical (creatinine, alanine aminotransferase (ALT), total cholesterol, alkaline phosphatase (ALP) and glucose) and dexamethasone suppression test), but they showed no significant changes. Thus, it was suspected that the animal had an uncommon endocrinopathy, DI. For its confirmation, it was made the water deprivation test with application of desmopressin acetate. The patient remained without access to water and without fluidtherapy with urethral sounding and bladder emptying. The measurement of urinary gravity and volume were made every hour for 12 h. After 8 h from the start of the test, it was made the application of desmopressin acetate (three drops in the conjunctival sac), because the animal began to exhibit tremors and muscle weakness (urine specific gravity: 1005). In this period, their body weight decreased 11.6%. After application of desmopressin, urine specific gravity increased gradually every hour, ending with urine specific gravity measurements of 1023, confirming the diagnosis of central DI. Discussion: The diagnosis of DI can be a challenge to the veterinary practitioner since it is a rare disease in small animals, and often is not included in the differential diagnoses. Furthermore, additional tests such as common hematological, biochemical and electrolyte profiles usually have normal results, or secondary influences of dehydration. The water deprivation test confirms the inability of the animal to concentrate urine in DI. However, this test is potentially dangerous because of the serious consequences of dehydration, requiring constant monitoring. In DI of central origin (DIC), the urinary concentration usually starts 1 to 3 h after administration of desmopressin acetate, and tends to be within the normal reference value, as can be observed in this case. Because there were not neurological signs, the final diagnosis of the animal was acquired DIC. DIC is acquired by the destruction of cells of supraoptic and paraventricular nuclei of the hypothalamus, or even, loss of the ducts that carry the anti-diuretic hormone (ADH) by the pituitary for secretion and storage. Desmopressin acetate (dDAVP), a synthetic analogue of vasopressin, was used for the initial treatment (three drops in the conjunctival sac, once a day) which controlled the PU/PD of the animal. After four months of treatment initiation, the animal has moved to a drop of the drug, twice a day. The dog of the present case has reported good prognosis, since small animals with acquired DIC become relatively asymptomatic in response to appropriate therapy.

Diabete insípido central em um cão

A case of central diabetes insipidus in a nine-year-old female dog is described. The dog presented intermitent polyuria and polydipsia in the past 18 months. In the clinical exam, complete blood count, alanine transaminase, alkaline phosphatase, BUN, creatinine, glucose and calcium dosages were normal. However, the specific urine gravity was low and presented the value 1002. The dog was unable to concentrate the urine during the seven hours of water deprivation test and presented 5% of dehydratation. The administration of desmopressin acetate elevated the specific urine gravity to 1028 five hours after the beginning of the treatment, confirming the diagnosis of diabetes insipidus of central origin.

Descreve-se um caso de diabete insípido central em um cão, fêmea, nove anos de idade, sem raça definida, com história de poliúria e polidipsia há 18 meses. Com o exame físico, nenhuma alteração sistêmica foi elucidada. Já nos exames laboratoriais complementares, observou-se policitemia e hiperproteinemia, e a densidade específica da urina (1002) encontrava-se abaixo do limiar fisiológico. O animal foi submetido à privação hídrica e se mostrou incapaz de concentrar a urina durante as sete horas observadas, tempo que levou para apresentar 5% de desidratação. Após isso, foi administrado acetato de desmopressina e, 5 horas após, a densidade estava em 1028, confirmando o diabete insípido de origem central. O animal recebeu terapia à base de acetato de desmopressina, apresentando melhora do quadro clínico.

Diabete insípido central em um cão

A case of central diabetes insipidus in a nine-year-old female dog is described. The dog presented intermitent polyuria and polydipsia in the past 18 months. In the clinical exam, complete blood count, alanine transaminase, alkaline phosphatase, BUN, creatinine, glucose and calcium dosages were normal. However, the specific urine gravity was low and presented the value 1002. The dog was unable to concentrate the urine during the seven hours of water deprivation test and presented 5% of dehydratation. The administration of desmopressin acetate elevated the specific urine gravity to 1028 five hours after the beginning of the treatment, confirming the diagnosis of diabetes insipidus of central origin.

Descreve-se um caso de diabete insípido central em um cão, fêmea, nove anos de idade, sem raça definida, com história de poliúria e polidipsia há 18 meses. Com o exame físico, nenhuma alteração sistêmica foi elucidada. Já nos exames laboratoriais complementares, observou-se policitemia e hiperproteinemia, e a densidade específica da urina (1002) encontrava-se abaixo do limiar fisiológico. O animal foi submetido à privação hídrica e se mostrou incapaz de concentrar a urina durante as sete horas observadas, tempo que levou para apresentar 5% de desidratação. Após isso, foi administrado acetato de desmopressina e, 5 horas após, a densidade estava em 1028, confirmando o diabete insípido de origem central. O animal recebeu terapia à base de acetato de desmopressina, apresentando melhora do quadro clínico.

Diabetes insípido em um cão

Background: Diabetes insipidus (DI) is a rare endocrine disorder in dogs altering the mechanism of retention and excretion of water, with concomitant polyuria and polydipsia (PU/PD), and low urine specifi c gravity. The water deprivation test followed by response to application of desmopressin is the diagnostic test for the disease. However, the literature is still scarce about laboratorial and clinical aspects of DI in small animals. Thus, the aim of this study is to report a case of DI in a canine, emphasizing its diagnosis through the water deprivation test.Case: A male mongrel dog, 5 years-old, not neutered, 13kg of body weight, was presented with intense PU/PD (500mL/kg/day of water consumption). Physical examination showed normal routine clinical parameters. Additional tests were asked (abdominal ultrasound, blood count, serum biochemical (creatinine, alanine aminotransferase (ALT), total cholesterol, alkaline phosphatase (ALP) and glucose) and dexamethasone suppression test), but they showed no signifi cant changes. Thus, it was suspected that the animal had an uncommon endocrinopathy, DI. For its confi rmation, it was made the water deprivation test with application of desmopressin acetate. The patient remained without access to water and without fluidtherapy with urethral sounding and bladder emptying. The measurement of urinary gravity and volume were made every hour