Design, synthesis, and evaluation of Bothrops venom serine protease peptidic inhibitors

In Central and South America, snakebite envenomation is mainly caused by Bothrops spp. snakes, whose venoms feature significant biochemical richness, including serine proteases. The available bothropic antivenoms are efficient in avoiding fatalities, but do not completely neutralize venom serine proteases, which are co-responsible for some disorders observed during envenomation. Methods: In order to search for tools to improve the antivenom's, 6-mer peptides were designed based on a specific substrate for Bothrops jararaca venom serine proteases, and then synthesized, with the intention to selectively inhibit these enzymes. Results: Using batroxobin as a snake venom serine protease model, two structurally similar inhibitor peptides were identified. When tested on B. jararaca venom, one of the new inhibitors displayed a good potential to inhibit the activity of the venom serine proteases. These inhibitors do not affect human serine proteases as human factor Xa and thrombin, due to their selectivity. Conclusion: Our study identified two small peptides able to inhibit bothropic serine proteases, but not human ones, can be used as tools to enhance knowledge of the venom composition and function. Moreover, one promising peptide (pepC) was identified that can be explored in the search for improving Bothrops spp. envenomation treatment.(AU)

Comparison of hemostatic efficacy of topical Ankaferd Blood Stopper on heparinized and nonheparinized rats in bleeding related to liver injury

Purpose: In this study, hemostatic efficacy of Ankaferd Blood Stopper (ABS), a new generation hemostatic agent, was compared in the presence of heparin effect. Methods: Forty-eight Wistar albino rats were divided into two main groups as heparinized and nonheparinized, and these two main groupswere divided into six subgroups as control, Surgicel and ABS (n = 8). Grade 2 liver injury was performed on rats as standard. All groups were compared in terms of weight, laceration surface area, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), bleeding time, bleeding amount, hemoglobin (Hb) levels, macroscopic and microscopic reactions to the agent used. Results: Whereas there was no statistically significant difference between weight, laceration surface area, PT, INR and preoperative Hb values in the heparinized and nonheparinized groups, postoperative Hb, bleeding time, bleeding amount and aPTT values were statistically different (p 0.05). In the heparin-hemostat interaction, the ABS group had the lowest bleeding in the heparinized group in terms of the amount of bleeding compared to the control and Surgicel groups (F = 0.764; p = 0.047). In macroscopic and microscopic comparison, there was no difference between the groups in terms of cell necrosis andfresh bleeding (p > 0.05), it was found that the Surgicel group had statistical significantly higher reaction scores (p < 0.05) than the other groups in terms of other parameters. Conclusions: Ankaferd Blood Stopper can be safely and effectively used in surgical practice and in patients with additional diseases requiring heparinization, since it causes minimal reaction in the liver and decreases the amount of bleeding especially in the heparinized group.(AU)

Design, synthesis, and evaluation of Bothrops venom serine protease peptidic inhibitors

In Central and South America, snakebite envenomation is mainly caused by Bothrops spp. snakes, whose venoms feature significant biochemical richness, including serine proteases. The available bothropic antivenoms are efficient in avoiding fatalities, but do not completely neutralize venom serine proteases, which are co-responsible for some disorders observed during envenomation. Methods: In order to search for tools to improve the antivenom's, 6-mer peptides were designed based on a specific substrate for Bothrops jararaca venom serine proteases, and then synthesized, with the intention to selectively inhibit these enzymes. Results: Using batroxobin as a snake venom serine protease model, two structurally similar inhibitor peptides were identified. When tested on B. jararaca venom, one of the new inhibitors displayed a good potential to inhibit the activity of the venom serine proteases. These inhibitors do not affect human serine proteases as human factor Xa and thrombin, due to their selectivity. Conclusion: Our study identified two small peptides able to inhibit bothropic serine proteases, but not human ones, can be used as tools to enhance knowledge of the venom composition and function. Moreover, one promising peptide (pepC) was identified that can be explored in the search for improving Bothrops spp. envenomation treatment.(AU)

Thromboelastometry assessment of mycophenolate mofetil effect on thrombotic risk in dogs with primary and secondary immune-mediated hemolytic anemia and by Erhlichia canis infection / [Avaliação por tromboelastometria do efeito do micofenolato de mofetila no risco trombótico em cães com anemia hemolítica imunomediada primária e secundária à infecção por Erhlichia canis]

This study aimed to identify, by means of thromboelastometry assessment, altered thrombotic risk in dogs with primary and secondary IMHA by E. canis infection after initiating the immunosuppressive therapy with mycophenolate mofetil. The animals' screening was based on complete blood count (CBC), biochemical and urine tests. Dogs with moderate to severe anemia (hematocrit ≤ 25%) which showed symptoms of immune-mediated hemolysis, such as spherocytosis, positive saline agglutination, bilirubinuria and/or hemoglobinuria, were included. Blood and urine samples were collected at two different moments. The first sample (M1) was collected at the time of diagnosis, when hematocrit was lower or equal to 25% before treatment with mycophenolate mofetil (Accord ®); the second sample (M2) was collected after treatment with mycophenolate mofetil, when hematocrit was greater or equal to 30%. Five out of the twelve animals selected died before the end of the study. No reduction in thrombotic risk was observed in the animals treated with mycophenolate mofetil. The animals that presented hypocoagulation at the time of diagnosis showed the worst prognosis, and their reticulocyte count displayed a better prognostic value than their erythrocytes count at the time of diagnosis.(AU)

O objetivo deste estudo foi esclarecer se há alteração do risco trombótico em cães com anemia hemolítica imunomediada primária e secundária a E.canis, avaliado por meio da tromboelastometria, após início de tratamento com micofenolato de mofetila. A seleção dos animais foi baseada na avaliação de hemograma, exame bioquímico e urinálise. Cães com anemia moderada a severa (hematócrito ≤ 25%), com sinais de hemólise imunomediada, como esferocitose, aglutinação em salina positivo, bilirrubinúria e/ ou hemoglobinúria, foram incluídos. As amostras de sangue e urina foram coletadas em dois momentos diferentes. A primeira amostra (M1) foi coletada no momento do diagnóstico, quando o hematócrito era igual ou inferior a 25%, sem fazer uso do micofenolato de mofetila (Accord®), e o segundo momento (M2), após tratamento com micofenolato de mofetila, quando o hematócrito era igual ou maior que 30%. Doze animais foram selecionados, cinco morreram antes do término do estudo. Não houve diminuição do risco trombótico entre os animais tratados com micofenolato de mofetila; os animais que apresentaram menor coagulabilidade apresentaram pior prognóstico, e a contagem de reticulócitos apresentou melhor valor prognóstico do que a contagem de hemácias no momento do diagnóstico.(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)

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)

Thrombin generation and thromboelastometry tests in dogs with chronic kidney disease / Testes de geração de trombina e tromboelastometria em cães com doença renal crônica

Patients with chronic kidney disease (CKD) have paradoxical hemostatic potential because they have bleeding episodes but are also prone to thrombosis. Few studies have evaluated blood viscoelastic properties in dogs with kidney disease; on the other hand, hypercoagulability has been observed in these patients. It is also emphasized that the platelet function and its participation in this process have not yet been fully understood. The objective of this study was to evaluate and compare the Thrombin Generation Test (TGT) and also viscoelastic properties of the blood measured by thromboelastometry (TEM) in dogs with proteinuria in CKD. Twenty healthy dogs (Control Group) and 19 dogs with CKD in stage III or IV, classified according to International Renal Interest Society - IRIS, were selected, and the reference test of urine protein:creatinine ratio (UPCR) should be greater than one (CKD group). Blood samples for TEM, thrombin generation, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and fibrinogen concentration was collected at a single time for both groups after inclusion criteria being confirmed. Statistical analysis was performed according to the distribution of variables at 5% significance level. Differences were observed between healthy dogs and those with proteinuria in CKD noted in TEM. The TGT was unable to differentiate between sick and healthy groups. However, when the nephropathy was stratified, increases in TTP and peak thrombin concentration by TGT were observed in females and dogs over 30 days of diagnosis of CKD. Both tests signaled a discrete state of hypercoagulability. In fact, TEM is more sensitive to detect hypercoagulability in dogs with CKD. However, the TGT has potential clinical application by allowing long-term sample storage.(AU)

Os pacientes com doença renal crônica (DRC) apresentam um potencial hemostático paradoxal, pois apresentam episódios de sangramento, mas também são propensos à trombose. Poucos estudos avaliaram as propriedades viscoelásticas sanguíneas em cães com doenças renais, entretanto, a hipercoagulabilidade já foi observada nestes pacientes. Ressalta-se ainda que a função plaquetária e sua participação neste processo ainda não foram totalmente esclarecidas. O objetivo foi avaliar e comparar o teste de geração de trombina (TGT) e as propriedades viscoelásticas sanguíneas medidas pela tromboelastometria (TEM) em cães com DRC proteinúrica. Foram selecionados 20 cães saudáveis (grupo controle) e 19 cães com DRC em estágios III ou IV classificados segundo o IRIS e a relação proteína/creatinina urinária maior que um (grupo DRC). As amostras de sangue para a realização da tromboelastometria (TEM), geração de trombina, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e concentração de fibrinogênio foram colhidas em momento único para ambos os grupos após os critérios de inclusão confirmados. A análise estatística foi realizada de acordo com a distribuição das variáveis, ao nível de 5% de significância. Foi observada diferença entre os cães saudáveis e os com DRC proteinúrica observados na TEM. O teste de geração de trombina não foi capaz de diferenciar os grupos doente e saudável. Entretanto, quando os nefropatas foram analisados de forma estratificada, foram observados aumentos do ETP e da concentração máxima de trombina (peak) pelo TGT em fêmeas e em cães com mais de 30 dias de diagnóstico da DRC. Ambos os testes sinalizando para um discreto estado de hipercoagulabiliade. A tromboelastometria é mais sensível para detectar a hipercoagulabilidade em cães com DRC. Entretanto, o teste de geração de trombina tem melhor aplicabilidade por permitir o armazenamento da amostra em longo prazo.(AU)

Thrombin generation and thromboelastometry tests in dogs with chronic kidney disease / Testes de geração de trombina e tromboelastometria em cães com doença renal crônica

Patients with chronic kidney disease (CKD) have paradoxical hemostatic potential because they have bleeding episodes but are also prone to thrombosis. Few studies have evaluated blood viscoelastic properties in dogs with kidney disease; on the other hand, hypercoagulability has been observed in these patients. It is also emphasized that the platelet function and its participation in this process have not yet been fully understood. The objective of this study was to evaluate and compare the Thrombin Generation Test (TGT) and also viscoelastic properties of the blood measured by thromboelastometry (TEM) in dogs with proteinuria in CKD. Twenty healthy dogs (Control Group) and 19 dogs with CKD in stage III or IV, classified according to International Renal Interest Society - IRIS, were selected, and the reference test of urine protein:creatinine ratio (UPCR) should be greater than one (CKD group). Blood samples for TEM, thrombin generation, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and fibrinogen concentration was collected at a single time for both groups after inclusion criteria being confirmed. Statistical analysis was performed according to the distribution of variables at 5% significance level. Differences were observed between healthy dogs and those with proteinuria in CKD noted in TEM. The TGT was unable to differentiate between sick and healthy groups. However, when the nephropathy was stratified, increases in TTP and peak thrombin concentration by TGT were observed in females and dogs over 30 days of diagnosis of CKD. Both tests signaled a discrete state of hypercoagulability. In fact, TEM is more sensitive to detect hypercoagulability in dogs with CKD. However, the TGT has potential clinical application by allowing long-term sample storage.(AU)

Os pacientes com doença renal crônica (DRC) apresentam um potencial hemostático paradoxal, pois apresentam episódios de sangramento, mas também são propensos à trombose. Poucos estudos avaliaram as propriedades viscoelásticas sanguíneas em cães com doenças renais, entretanto, a hipercoagulabilidade já foi observada nestes pacientes. Ressalta-se ainda que a função plaquetária e sua participação neste processo ainda não foram totalmente esclarecidas. O objetivo foi avaliar e comparar o teste de geração de trombina (TGT) e as propriedades viscoelásticas sanguíneas medidas pela tromboelastometria (TEM) em cães com DRC proteinúrica. Foram selecionados 20 cães saudáveis (grupo controle) e 19 cães com DRC em estágios III ou IV classificados segundo o IRIS e a relação proteína/creatinina urinária maior que um (grupo DRC). As amostras de sangue para a realização da tromboelastometria (TEM), geração de trombina, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e concentração de fibrinogênio foram colhidas em momento único para ambos os grupos após os critérios de inclusão confirmados. A análise estatística foi realizada de acordo com a distribuição das variáveis, ao nível de 5% de significância. Foi observada diferença entre os cães saudáveis e os com DRC proteinúrica observados na TEM. O teste de geração de trombina não foi capaz de diferenciar os grupos doente e saudável. Entretanto, quando os nefropatas foram analisados de forma estratificada, foram observados aumentos do ETP e da concentração máxima de trombina (peak) pelo TGT em fêmeas e em cães com mais de 30 dias de diagnóstico da DRC. Ambos os testes sinalizando para um discreto estado de hipercoagulabiliade. A tromboelastometria é mais sensível para detectar a hipercoagulabilidade em cães com DRC. Entretanto, o teste de geração de trombina tem melhor aplicabilidade por permitir o armazenamento da amostra em longo prazo.(AU)

Miocardiopatia hipertrófica relacionada ao tromboembolismo arterial em felinos

As miocardiopatias hipertróficas observadas frequentemente, apresentam complexa fisiopatologia clínica e não são completamente elucidadas. Uma das causas conhecidas para a doença é a presença da mutação no gene MYPBC3, responsável pela contractilidade e relaxamento dos sarcômeros no miocárdio. Uma das consequências relacionadas ao desenvolvimento destas doenças é a presença e formação de trombos, por ocorrência de estase sanguínea e exposição de tromboplastina tecidual. A principal ferramenta diagnóstica para a prevenção ou tratamento da doença é o ecocardiograma. Esta revisão elucida aspectos sobre a fisiopatologia da doença e a sua relação com a presença ou ausência de tromboembolismo.(AU)

The hypertrophic cardiomyopathy is observed frequently in clinical practice, is a disease with a complex clinical pathophysiology and are not completely elucidated. A principal cause was reported for this disease is the presence of the mutation in the MYPBC3 gene, responsible for the capacity of contractility and relaxation of sarcomeres in the myocardio. One of the consequences related to the development of these diseases is the presence and formation of thromboses, due to the occurrence of blood stasis in the left atrium and exposure of tissue thromboplastin. The main diagnostic tool for the prevention or treatment of the disease is the echocardiogram. This review elucidates aspects about the pathophysiology of the disease and its relation to the presence or absence of thromboembolism.(AU)

Miocardiopatia hipertrófica relacionada ao tromboembolismo arterial em felinos

As miocardiopatias hipertróficas observadas frequentemente, apresentam complexa fisiopatologia clínica e não são completamente elucidadas. Uma das causas conhecidas para a doença é a presença da mutação no gene MYPBC3, responsável pela contractilidade e relaxamento dos sarcômeros no miocárdio. Uma das consequências relacionadas ao desenvolvimento destas doenças é a presença e formação de trombos, por ocorrência de estase sanguínea e exposição de tromboplastina tecidual. A principal ferramenta diagnóstica para a prevenção ou tratamento da doença é o ecocardiograma. Esta revisão elucida aspectos sobre a fisiopatologia da doença e a sua relação com a presença ou ausência de tromboembolismo.

The hypertrophic cardiomyopathy is observed frequently in clinical practice, is a disease with a complex clinical pathophysiology and are not completely elucidated. A principal cause was reported for this disease is the presence of the mutation in the MYPBC3 gene, responsible for the capacity of contractility and relaxation of sarcomeres in the myocardio. One of the consequences related to the development of these diseases is the presence and formation of thromboses, due to the occurrence of blood stasis in the left atrium and exposure of tissue thromboplastin. The main diagnostic tool for the prevention or treatment of the disease is the echocardiogram. This review elucidates aspects about the pathophysiology of the disease and its relation to the presence or absence of thromboembolism.

Aplicação De Diferentes Pinças Hemostáticas Em Veias De Equinos: Estudo Morfológico / Application Of Different Hemostatic Clamps In Horses Veins: A Morphological Study / Aplicación De Diferentes Pinzas Hemostaticas En Venas De Equinos: Estudio Morfologico

Foi realizada a avaliação morfológica da veia cefálica submetida à pinçamento em cinco equinos hígidos. Foram testadas as pinças hemostáticas: Diffenbach bulldog, De Bakey bulldog, Rochester reta e De Bakey com cremalheira. Após 15 minutos da aplicação das referidas pinças, foi realizada a flebectomia parcial e coletadas as amostras referentes a cada segmento do vaso pinçado e do segmento controle sem pinçamento. Das peças procedeu-se as preparações histológicas dos segmentos da veia nas colorações de Hematoxilina-Eosina e Tricrômio de Masson. Os cortes histológicos foram avaliados por microscopia óptica. Foi realizada análise morfológica das veias, utilizando para isto uma escala de avaliação de lesões vasculares após pinçamento. As pinças com serrilhamento transversal e fechamento tipo cremalheira causaram as maiores alterações, observou se marcada vacuolização das células musculares e desarranjo na túnica media com perda marcada das células endoteliais da túnica intima do vaso estudado. (AU)

Morphologic evaluation of the cephalic vein of five healthy horses submitted to clamping was done. Hemostatic clamps tested were Dieffenbach bulldog, De Bakey bulldog, Rochester straight and De Bakey with ratchets. Fifthen minutes after mentioned clamps were applied partial phlebotomy was performed and histologic sections of the veins were prepared and stained with Hematoxylin-Eosin and Masson Trichrome. After the stained preparations were evaluated by light microscopy. The morphological analysis of the veins was performed using a rating scale of vascular lesions after clamping. The hemostatic clamps with transverse serration and ratcheted mechanism caused major changes, pronounced vacuolization of the muscle cells, derangement of the medium tunic and marked loss of endothelial cells of the intima tunic was observed in the vessel studied.(AU)

Evaluacion morfológica de la vena cefálica de cinco equinos saludables sometida a pinzamiento fue realizada. Las pinzas hemostáticas evaluadas fueron Diffenbach bulldog, De Bakey Bulldog, Rochester recta y De Bakey cremallera. Despues de 15 minutos de aplicadas las pinzas mencionadas fue realizada la flebectomía y los diferentes cortes histológicos de las venas fueron preparados y coloraciones de Hematoxilina-Eosina y Tricrimico de Mansson fueron evaluadas por microscopia de luz. El análisis morfológico de la vena fue realizado usando una escala de lesiones vasculares post pinzamiento. Las pinzas hemostáticas con serrillamiento transversal y cierre de tipo cremallera fueron las que generaron mas cambios, marcada vacuolizacion de las células musculares en la túnica media y perdida evidente del numero de células endoteliales en la túnica intima de la vena estudiada.(AU)

Aplicação De Diferentes Pinças Hemostáticas Em Veias De Equinos: Estudo Morfológico / Application Of Different Hemostatic Clamps In Horse’s Veins: A Morphological Study / Aplicación De Diferentes Pinzas Hemostaticas En Venas De Equinos: Estudio Morfologico

Foi realizada a avaliação morfológica da veia cefálica submetida à pinçamento em cinco equinos hígidos. Foram testadas as pinças hemostáticas: Diffenbach bulldog, De Bakey bulldog, Rochester reta e De Bakey com cremalheira. Após 15 minutos da aplicação das referidas pinças, foi realizada a flebectomia parcial e coletadas as amostras referentes a cada segmento do vaso pinçado e do segmento controle sem pinçamento. Das peças procedeu-se as preparações histológicas dos segmentos da veia nas colorações de Hematoxilina-Eosina e Tricrômio de Masson. Os cortes histológicos foram avaliados por microscopia óptica. Foi realizada análise morfológica das veias, utilizando para isto uma escala de avaliação de lesões vasculares após pinçamento. As pinças com serrilhamento transversal e fechamento tipo cremalheira causaram as maiores alterações, observou se marcada vacuolização das células musculares e desarranjo na túnica media com perda marcada das células endoteliais da túnica intima do vaso estudado.

Morphologic evaluation of the cephalic vein of five healthy horses submitted to clamping was done. Hemostatic clamps tested were Dieffenbach bulldog, De Bakey bulldog, Rochester straight and De Bakey with ratchets. Fifthen minutes after mentioned clamps were applied partial phlebotomy was performed and histologic sections of the veins were prepared and stained with Hematoxylin-Eosin and Masson Trichrome. After the stained preparations were evaluated by light microscopy. The morphological analysis of the veins was performed using a rating scale of vascular lesions after clamping. The hemostatic clamps with transverse serration and ratcheted mechanism caused major changes, pronounced vacuolization of the muscle cells, derangement of the medium tunic and marked loss of endothelial cells of the intima tunic was observed in the vessel studied.

Evaluacion morfológica de la vena cefálica de cinco equinos saludables sometida a pinzamiento fue realizada. Las pinzas hemostáticas evaluadas fueron Diffenbach bulldog, De Bakey Bulldog, Rochester recta y De Bakey cremallera. Despues de 15 minutos de aplicadas las pinzas mencionadas fue realizada la flebectomía y los diferentes cortes histológicos de las venas fueron preparados y coloraciones de Hematoxilina-Eosina y Tricrimico de Mansson fueron evaluadas por microscopia de luz. El análisis morfológico de la vena fue realizado usando una escala de lesiones vasculares post pinzamiento. Las pinzas hemostáticas con serrillamiento transversal y cierre de tipo cremallera fueron las que generaron mas cambios, marcada vacuolizacion de las células musculares en la túnica media y perdida evidente del numero de células endoteliales en la túnica intima de la vena estudiada.

DETERMINAÇÃO DOS INTERVALOS DE REFERÊNCIA DAS VARIÁVEIS TROMBOELASTOGRÁFICAS SEM O USO DE ATIVADORES EM DIFERENTES AMOSTRAS SANGUÍNEAS DE CÃES HÍGIDOS

O sistema hemostático compreende um conjunto de eventos fisiológicos e complexos do organismo. Este previne o escape de sangue a partir dos vasos sanguíneos e a formação de trombos que afetarão o fluxo sanguíneo. Para manter a fluidez do sangue nos vasos sanguíneos, é necessária a interação em homeostase de vários componentes, como a parede vascular, plaquetas, fatores de coagulação, substâncias anticoagulantes naturais e substâncias fibrinolíticas, entre outros. A avaliação de desordens hemostáticas é realizada por meio de exames laboratoriais geralmente subdivididos em testes convencionais e em testes viscoelásticos, como a tromboelastografia (TEG). O presente estudo teve como objetivo evidenciar as variáveis tromboelastográficas de cães hígidos utilizando diferentes amostras sanguíneas, como o sangue total fresco (STF), sangue total com citrato de sódio a 3,2% (STC), plasma fresco (PF) e plasma fresco congelado (PFC). A finalidade foi estabelecer intervalo de referência (IR) para tais variáveis em cães hígidos e verificar se o tipo de amostra e o método de conservação da amostra alteram o traçado tromboelastográfico. Para este projeto, foram selecionados 22 cães sadios oriundos do serviço de atendimento clínico do Núcleo de Atendimento Veterinário do Centro Universitário Moura Lacerda, Ribeirão Preto/SP, que buscaram o atendimento para avaliações rotineiras anuais de sanidade. As diferentes amostras sanguíneas foram coletadas por meio de venopunção jugular e submetidas à análise tromboelastográfica em diferentes circunstâncias. Para determinação dos IR, foi realizado teste t Student com intervalo de confiança (IC) de 95%, valor-p 0,05 e teste de Fisher para verificar homogeneidade. Além disso, foi realizado teste de Shapiro Wilk para verificação de normalidade e com auxílio de gráficos box plot para detecção e exclusão de valores extremos (outliers). Os dados foram processados no software estatístico livre RGui versão 4.0.0 (R Core Team (2020). O conjunto de eventos do sistema hemostático, necessita de avaliação laboratorial robusta, como testes viscoelásticos, para melhor interpretação. Portanto, realizar tromboelastografia em diferentes amostras sanguíneas, bem como, determinar intervalo de referência para as variáveis TEG das diferentes amostras, mostra avanço para a realização do TEG em laboratórios clínicos veterinários. A obtenção de IR para diferentes tipos de amostras, possibilita o acesso ao exame tromboelastográfico em diferentes circunstâncias. O presente projeto mostrou ser possível e viável a realização da tromboelastografia em diferentes amostras sanguíneas e todas elas representam o paciente animal de maneira confiável.

The hemostatic system comprises a set of physiological and complex events in the body. This prevents the leakage of blood from the blood vessels and the formation of thrombi that will affect blood flow. To maintain the fluidity of blood in blood vessels, it is necessary to interact in homeostasis of various components, such as the vascular wall, platelets, coagulation factors, natural anticoagulant substances and fibrinolytic substances, among others. The evaluation of hemostatic disorders is performed through laboratory tests, usually subdivided into conventional tests and viscoelastic tests, such as thromboelastography (TEG). The present study aimed to evidence the thromboelastographic variables of healthy dogs using different blood samples, such as fresh whole blood (FTS), whole blood with 3.2% sodium citrate (STC), fresh plasma (FP) and fresh plasma frozen (PFC). The purpose was to establish a reference interval (RI) for such variables in healthy dogs and to verify whether the type of sample and the method of sample conservation alter the thromboelastographic tracing. For this project, 22 healthy dogs were selected from the clinical care service of the Center for Veterinary Care of the Moura Lacerda University Center, Ribeirão Preto/SP, which sought care for routine annual health assessments. Different blood samples were collected through jugular venipuncture and submitted to thromboelastographic analysis under different circumstances. To determine the RI, Student's t test was performed with a confidence interval (CI) of 95%, p-value 0.05 and Fisher's test to verify homogeneity. In addition, the Shapiro Wilk test was performed to verify normality and with the aid of box plot graphics for detection and exclusion of extreme values (outliers). Data were processed in the free statistical software RGui version 4.0.0 (R Core Team (2020). The set of events of the hemostatic system requires robust laboratory evaluation, such as viscoelastic tests, for better interpretation. Therefore, perform thromboelastography in different samples blood tests, as well as determining the reference interval for the TEG variables of different samples, shows advances in the performance of TEG in clinical veterinary laboratories. This project showed that it is possible and viable to perform thromboelastography in different blood samples and all of them represent the animal patient reliably.

Applying and cutting device for tie-wraps during laparoscopic ovariectomy in standing mares / Dispositivo para aplicação e cortes de lacres de pressão durante ovariectomia laparoscópica com éguas em estação

Background: Laparoscopic ovariectomy it is used more than 20 years in veterinary medicine, however, information of this technique in Brazil are rare. Also, the cost for his execution are high, specially the ovarian hemostasis procedure, that depends on highly specialized surgical instruments. The goal of this study is show the results achieved during laparoscopic ovariectomy in mares using a device to apply and cut tie-wraps, developed by the authors and that is in a patent process. Materials, Methods & Results: Four mares with ovarian pathologies were selected for a standing unilateral ovariectomy procedure and access to cavity occurred through three laparoscopic portals. The vessels and ligament were dissected to allow positioning of a polyamide tie-wrap by the device for cutting and applying those seals. Occlusion was made by pushing, and cutting through a rotation on the tie latch. Then, the mesovarium was cut with laparoscopic scissors and ovary removed by a communication between two accesses. Total surgical time and the equipment handling were noted. The average duration of surgical procedures was 80 ± 12.35 min and device handling time since its external preparation, application and cutting the polyamide tie-wraps was 3.4 ± 2.63 min. Only in one of four animals it was necessary to apply more than one tie, since the first promoted incomplete vessels occlusion [...](AU)

Applying and cutting device for tie-wraps during laparoscopic ovariectomy in standing mares / Dispositivo para aplicação e cortes de lacres de pressão durante ovariectomia laparoscópica com éguas em estação

Background: Laparoscopic ovariectomy it is used more than 20 years in veterinary medicine, however, information of this technique in Brazil are rare. Also, the cost for his execution are high, specially the ovarian hemostasis procedure, that depends on highly specialized surgical instruments. The goal of this study is show the results achieved during laparoscopic ovariectomy in mares using a device to apply and cut tie-wraps, developed by the authors and that is in a patent process. Materials, Methods & Results: Four mares with ovarian pathologies were selected for a standing unilateral ovariectomy procedure and access to cavity occurred through three laparoscopic portals. The vessels and ligament were dissected to allow positioning of a polyamide tie-wrap by the device for cutting and applying those seals. Occlusion was made by pushing, and cutting through a rotation on the tie latch. Then, the mesovarium was cut with laparoscopic scissors and ovary removed by a communication between two accesses. Total surgical time and the equipment handling were noted. The average duration of surgical procedures was 80 ± 12.35 min and device handling time since its external preparation, application and cutting the polyamide tie-wraps was 3.4 ± 2.63 min. Only in one of four animals it was necessary to apply more than one tie, since the first promoted incomplete vessels occlusion [...]

AVALIAÇÃO DE PERFIL HEMOSTÁTICO EM CÃES EM QUADRO DE INJÚRIA RENAL AGUDA NÃO SUBMETIDOS À TERAPIA DIALÍTICA

A injúria renal aguda (IRA) representa uma grande casuística na medicina veterinária e está associada à elevada mortalidade. Em humanos, sabe-se que os quadros de IRA podem levar a alterações hemostáticas, as quais podem aumentar o tempo de permanência do paciente em hospitalização e elevar a mortalidade. Entretanto, a ocorrência de distúrbios coagulatórios em cães com IRA ainda não é bem compreendida. O objetivo deste estudo foi avaliar o perfil hemostático de cães em IRA, devidamente estadiados e se esses pacientes apresentam distúrbios de hemostasia. Além disso, correlacionar as variáveis testadas com a intensidade da azotemia e com o risco de óbito. O estudo contou com 42 pacientes, sendo 14 no grupo controle, 14 no grupo IRIS III e 14 no grupo IRIS IV, de diferentes, sexos, raças e faixas etárias. Os marcadores hemostáticos testados foram Dímero-D, TP, TTPa, TT e fibrinogênio, sendo que foram comparados um kit para Dímero-D em humanos com um kit para cães. O Dímero-D e os demais marcadores hemostáticos apresentaram-se aumentados nos pacientes em IRA de estágios III e IV, porém não houve correlação entre esses marcadores e a intensidade da azotemia. Entretanto, o Dímero-D apresentou forte correlação positiva com as enzimas hepáticas e com a RPCU. Todos os marcadores hemostáticos testados apresentaram correlação positiva com o risco de óbito do paciente. Além disso, os dois testes para Dímero-D avaliados, foram eficazes e apresentaram correlação positiva. O aumento dos marcadores hemostáticos e Dímero-D e a correlação entre RPCU e Dímero-D, sugerem uma tendência ao estado de hipercoagulabilidade nos cães avaliados, com IRA em estágio III e IV. O Dímero-D apresentou forte correlação positiva com o risco de morte dos pacientes, evidenciando seu potencial como marcador de prognóstico.

Acute kidney injury (AKI) represents a large sample in veterinary medicine and is associated with a high mortality. In humans it is known that AKI can lead to hemostatic changes which can increase the length of stay of the patient in hospital and increase mortality. However, the occurrence of coagulation disorders in dogs with AKI is still not well understood. The aim of this study was to evaluate the hemostatic profile of dogs in AKI duly staged and whether these patients present hemostasis disorders. In addition, correlate the variables tested with the intensity of azotemia and the risk of death. The study included 42 patients, 14 in the control group, 14 in the IRIS group III and 14 in the IRIS group IV with different genders, races and age groups. The tested hemostatic markers were D-Dimer, TP, TTPa, TT and fibrinogen and a kit for D-Dimer in humans was compared with a kit for dogs. D-Dimer and other hemostatic markers were increased in patients with stage III and IV but there was no correlation between these markers and azotemia intensity. However, D-Dimer showed a strong positive correlation with liver enzymes and with UPCR. All tested hemostatic markers were positively correlated with the patient's risk of death. In addition, the two tests for D-Dimer evaluated were effective and showed a positive correlation. The increase in hemostatic and D-Dimer markers and the correlation between UPCR and D-Dimer suggest a tendency to a hypercoagulable state in the evaluated dogs, with IRIS stage III and IV. The D-Dimer showed a strong positive correlation with the risk of death of patients, showing its potential as a prognostic marker

The effects of ankaferd blood stopper and microporous polysaccharide hemospheres on epidural fibrosis in rat laminectomy model

PURPOSE: To investigate whether topically administered hemostatic agents ankaferd blood stopper and microporous polysaccharide hemospheres can decrease epidural fibrosis after laminectomy in rats. METHODS: Eighteen adult male Sprague-Dawley rats were equally and randomly divided into three groups. In the treatment groups, ankaferd blood stopper and microporous polysaccharide hemospheres topically administrated upon duramater surface after laminectomy. Fibroblast count, epidural fibrosis and arachnoidal involvement were evaluated and graded histopathologically. RESULTS: Our data revealed that the count of fibroblasts, the grading of epidural fibrosis and arachnoideal involvement in the rats treated with microporous polysaccharide hemospheres were significantly less than the control group. Although the arachnoideal involvement in ankaferd blood stopper group were significantly less than the control group, there were no statistical differences when comparing the grading of epidural fibrosis and the fibroblasts count between the treatment groups and the control group. CONCLUSION: The ankaferd blood stopper and microporous polysaccharide hemospheres reduced epidural fibrosis and arachnoideal involvement after laminectomy in rats.(AU)

GERAÇÃO DE TROMBINA EM CÃES COM HIPERADRENOCORTICISMO ENDÓGENO

O estado de hipercoagulabilidade é uma condição grave que pode levar a um quadro de trombose e/ou coagulação intravascular disseminada. Diversas doenças estão associadas com seu desenvolvimento, porém, os exames de hemostasia convencionais são pouco sensíveis na detecção do risco trombótico. Um dos testes mais estudados nos últimos anos é a geração de trombina, método que consegue avaliar o potencial endógeno da hemostasia global. O hiperadrenocorticismo (HAC) é uma endocrinopatia de ocorrência comum em cães que pode desencadear um estado de hipercoagulabilidade secundária ao hipercortisolismo. Os mecanismos fisiopatológicos são diversos e alguns deles ainda não são bem compreendidos. O objetivo deste estudo foi avaliar a aplicabilidade do teste de geração de trombina (TGT) para detectar alterações compatíveis com hipercoagulabilidade em cães com hiperadrenocorticismo endógeno, assim como correlacionar com um perfil hemostático compreendido por fibrinogênio, antitrombina (AT), dímero-D, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPa), e exames gerais de rotina para desvendar possíveis mecanismos protrombóticos. A maioria dos cães apresentou pelo menos uma alteração no perfil hemostático e/ou TGT. O TGT realizado em altas concentrações de fator tissular mostrou incremento de ETP (P= 0.0239) e peak (P= 0.0281) nos cães com HAC. O fibrinogênio (P = <0.0001) e AT (P = 0.0444), apresentaram um aumento significativo no grupo com HAC, e o TP (P = 0.0046) e TTPa (P = 0.0002) uma diminuição. Os níveis basais de cortisol se correlacionaram de forma positiva com os níveis de fibrinogênio (r = 0.4503; P = 0.0355) e de forma negativa com os níveis de AT (r = -0.4580; P = 0.0280). O fibrinogênio e o hematócrito se correlacionaram negativamente (r = -0.4853; P = 0.0076). O estudo mostrou que os cães com HAC endógeno apresentam uma maior geração de trombina, no entanto, o TGT realizado com baixa concentração de fator tissular não foi adequada para detectar essas alterações. O grau de hipercortisolemia influencia os níveis de AT e fibrinogênio. A proteinúria parece não determinar os níveis de AT e os cães com HAC mostraram uma diminuição do TP e TTPa.

The hypercoagulable state is a serious condition that can lead to thrombosis and/or disseminated intravascular coagulation. Several diseases are associated with its development; however, conventional coagulation tests are unable to detect thrombotic risk. For the past few years, the thrombin generation test (TGA) has become one of the most studied methods for evaluating global hemostasis. Hyperadrenocorticism (HAC) is a common canine endocrinopathy that have been associated with hypercoagulability. However, the pathophysiological mechanisms are diverse and some of them are still misunderstood. The objective of this study was to evaluate the applicability of TGA for detecting compatible alterations with a hypercoagulable tendency and to correlate with an hemostatic profile comprised of fibrinogen, antithrombin (AT), D-dimer, prothrombin time (PT) activated partial thromboplastin time (aPPT), and routine laboratory tests for elucidating possible prothrombotic mechanisms. The majority of dogs (80.6%) presented at least one alteration of the hemostatic profile and/or TGA parameters. TGA at high concentration of activator showed significantly higher ETP (P= 0.0239) and peak (P= 0.0281) in Cushing patients. Fibrinogen (P = <0.0001) and AT (P = 0.0444) activity were significantly higher in the HAC group, while PT (P = 0.0046) and aPTT (P = 0.0002) were lower. Basal cortisol levels correlated positively with fibrinogen levels (r = 0.4503; P = 0.0355) and negatively with AT values (r = -0.4580; P = 0.0280). Fibrinogen and hematocrit values showed a negative correlation (r = -0.4853; P = 0.0076). Our study showed that dogs with HAC presented higher thrombin generation, however, TGA performed with lower concentrations of tissue factor were inadequate for assessing hypercoagulability. Degree of hypercortisolism influences AT and fibrinogen levels. Proteinuria does not appear to determine AT activity and dogs with HAC showed a significantly shortened PT and aPTT.

The use of cryoprecipitate in a dog with acute hemorrhage: case report / Uso de crioprecipitado em cão com hemorragia aguda: relato de caso

It is reported the case of the use of cryoprecipitate in a canine patient, Yorkshire Terrier, who presented acute heavy bleeding disorder during arthroplasty procedure. At the time of bleeding disorder the patient had values of activated partial thromboplastin time (aPTT) above 240 seconds, and prothrombin time (PT) of 14.9 seconds. It was opted for the use of plasma components to correct the bleeding disorders, and since the patient had low weight (4.8kg), it was decided by the transfusion of one unit of cryoprecipitate (20 mL), quickly (20 minutes), even during surgery. The aPTT and PT post-transfusion values were 45.5 and 10.2 seconds respectively, with rapid control of bleeding. On return after 13 days the values of APTT and PT were within the normal range for the species. Because it contains high concentration of clotting factors and reduced volume, cryoprecipitate may be a good choice for patients with secondary bleeding disorders, especially in small animals. The effectiveness in transfusion therapy directed to the rational use of blood components illustrates the need for knowledge of the different blood components and individual study of each case.(AU)

Relata-se o caso do uso de crioprecipitado em um paciente canino, Yorkshire Terrier, que apresentou sangramento agudo intenso durante procedimento de artroplastia. No momento do distúrbio hemorrágico o paciente possuía valores de tromboplastina parcial ativada (TTPA) acima de 240 segundos, e de tempo de protrombina (TP) de 14,9 segundos. Optou-se pelo uso de hemocomponentes plasmáticos a fim de corrigir os distúrbios hemorrágicos, e uma vez que o paciente possuía peso reduzido (4,8kg), foi decidido pela transfusão de uma unidade de crioprecipitado (20 mL), de forma rápida (20 minutos), ainda no trans-operatório. Os valores de TTPA e TP pós-transfusionais foram de 45,5 e 10,2 segundos, respectivamente, com rápido controle do sangramento. No retorno após 13 dias os valores de TTPA e TP estavam dentro dos valores de normalidade para a espécie. Conclui-se que o crioprecipitado ofereceu os fatores de coagulação necessários para correção do distúrbio hemorrágico, controlando o sangramento e melhorando os valores de TTPA e TP. Por conter alta concentração de fatores de coagulação e volume reduzido, o crioprecipitado pode ser uma boa escolha para pacientes com coagulopatias secundárias, especialmente em animais de pequeno porte. A eficácia na terapia transfusional direcionada com o uso racional do melhor hemocomponente para o caso ilustra a necessidade de conhecimento dos diferentes hemocomponentes e estudo individual dos casos.(AU)

Valores de Referência para tempos de coagulação em uma população de cães de Porto Alegre, RS, Brasil / Reference values for coagulation time of dogs in Porto Alegre, RS, Brazil

Background: Prothrombin time (PT) and activated partial thromboplastin time (PTT) are screening tests for coagulopathies in dogs. Both tests measure the clotting ability by the activation of different parts of the coagulation cascade. These tests vary widely in terms of reference parameters, mainly due the considerable diversity of reagents and analyzers available. In addition, there are many variations inherent to different populations, and little has been published about coagulation reference parameters for the local dog population. The main objective of the present study was to determine a clotting time reference range of a dog population in Porto Alegre, Rio Grande do Sul, Brazil.Materials, Methods & Results: Hemostatic reference range was determined from citrated plasma of 268 clinically heathy dogs of both genders. The animals did not present bleeding diathesis or thrombocytopenia history. All dogs were previously submitted to clinical examination (cardiopulmonary auscultation, abdominal palpation, and rectal temperature) and laboratory screening (complete blood count, creatinine, albumin, and alanine aminotransferase). PT and PTT of 71 and 258 samples were measured, respectively. Blood samples were collected into 2.7 mL 3.2 % sodium citrate tubes (9 parts blood : 1 part citrate) by vacuum. Blood samples were centrifuged; the plasma was harvested and stored at -30 °C upon analyses. All analyses were performed using the viscosity detection method in semi-automatic coagulometer according to manufacturers guidelines. The reference ranges were determined in accordance with the American Society for Veterinary Clinical Pathology. The PT and PTT reference ranges were between 6.06 to 9.32 s and between 15.25 to 24.57 s, respectively.Discussion: The increased activity of the extrinsic pathway clotting factor generates narrow values in the PT assay, in comparison to PTT results.[...](AU)