Risco trombótico em cães com anemia hemolítica imunomediada primária e secundária a E. canis sob tratamento com micofenolato de mofetila
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Data
2018-07-30
Autores
Gorenstein, Tatiana Geraissate
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Universidade Estadual Paulista (Unesp)
Resumo
A anemia hemolítica imunomediada (AHIM) é o distúrbio imunológico de maior prevalência em cães. Caracteriza-se como uma hipersensibilidade do tipo II, que leva a destruição prematura de hemácias. Dentre as principais complicações, o estado de hipercoagulabilidade predispondo a coagulação intravascular disseminada e o tromboembolismo pulmonar é a mais importante, sendo a causa de óbito em mais de 80% dos casos. A AHIM primária não pode ser associada a causa predisponente óbvia, além de apresentar predisposição racial, portanto trata-se de um diagnóstico de exclusão. A AHIM secundária está relacionada a diversos agentes, dentre eles os infecciosos, destacando-se a erlichiose; neoplásicos; medicamentosos e os causados por defeitos intrínsecos. O diagnóstico de AHIM é realizado através da constatação de um ou mais desses sinais: moderada a grave anemia (hematócrito < 30 - 25%), evidências de hemólise (hemoglobinúria ou bilirrubinúria) e presença de anticorpos na hemácia (caracterizado a partir da autoaglutinação, esferocitose, teste de Coombs positivo ou citometria de fluxo). O tratamento é direcionado a supressão da resposta imune, sendo os corticosteroides e outros imunossupressores, tais como ciclosporina e micofenolato de mofetila, os fármacos de predileção. Objetivou-se com esta pesquisa esclarecer se há alteração do risco trombótico após o início da terapia imunossupressora com micofenolato de mofetila por meio da tromboelastometria em animais com AHIM primária e secundária a E.canis. Os animais em estudo foram submetidos a hemograma, contagem de reticulócitos, pesquisa de esferocitose, bioquímico sérico, exame de urina, relação proteína creatinina urinária, testes de coagulação, tromboelastometria; PCR para E. sp, E. canis e B. canis; sorologia para Leptospira spp e ultrassonografia abdominal. Foram selecionados 12 cães com diagnóstico de AHIM e realizado exame tromboelastométrico em dois momentos: antes do início do tratamento com micofenolato de mofetila, quando o paciente fazia uso de doxiciclina, omeprazol e prednisolona (M1) e após a adição do micofenolato de mofetila ao protocolo acima citado, quando houve melhora clínica e hematológica (M2). Cinco animais vieram a óbito antes do momento 2. A comparação entre as médias dos dois momentos do grupo dos sobreviventes foi avaliada pelo teste de Wilcox e para a comparação entre o momento 1 do grupo de sobreviventes e de óbitos foi utilizado o teste não paramétrico de Mann Whitney, ambos ao nível de 5% de significância. Nas condições em que foi realizado o presente estudo, é possível concluir que não há 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.
Immune-mediated hemolytic anemia (IMHA) is the most prevalent immune disorder in dogs. This condition is characterized as a type II hypersensitivity and leads to the premature destruction of red blood cells. Among the main complications, hypercoagulability, which predisposes dogs to disseminated intravascular coagulation and pulmonary thromboembolism, is the most important and leading cause of death in more than 80% of cases. Primary IMHA cannot be associated with an obvious predisposition, besides breed predilection, because of this it is a diagnostic exclusion. Secondary IMHA is related to several agents, and among the infectious ones, ehrlichiosis stands out. Animal selection for this study was based on hematological, biochemical, and urine tests. Dogs with moderate to severe anemia (hematocrit ≤ 25%), with symptoms of immune-mediated hemolysis, such as spherocytosis, positive saline agglutination, bilirubinuria and/or hemoglobinuria, were included. The treatment is directed towards immune response suppression, for which glucocorticoids and mycophenolate mofetil are frequently used. This study aimed to clarify whether the thrombotic risk changes after the initiation of immunosuppressive therapy with mycophenolate mofetil, through thromboelastometry, in animals with primary IMHA and secondary to E. canis infection. The animals under study were submitted to hemogram, reticulocyte count, spherocytosis screening, serum biochemistry, urinalysis, urinary protein/creatinine ratio, coagulation tests, thromboelastometry; PCR for E. sp, E. canis and B. canis; serology for Leptospira spp and abdominal ultrasonography. Twelve dogs with a diagnosis of IMHA were selected and a thromboelastic examination was performed at two moments: before the start of treatment with mycophenolate mofetila, when the patient used doxycycline, omeprazole and prednisolone (M1) and after the addition of mycophenolate mofetila to the protocol mentioned above, when there was clinical and hematological improvement (M2). Five animals died before moment 2. The Willcox nonparametric test was used to compare the two moments of the surviving group, and the nonparametric Mann-Whitney test was used to compare the moment 1 of the surviving group with the death group, both with 5% significance value. No change in the coagulation state of animals treated with mycophenolate mofetil was observed. The animals that showed lower coagulation at the time of diagnosis exhibited a worse prognosis, and the reticulocyte count showed a better prognostic value than the red blood cell count at the time of diagnosis
Immune-mediated hemolytic anemia (IMHA) is the most prevalent immune disorder in dogs. This condition is characterized as a type II hypersensitivity and leads to the premature destruction of red blood cells. Among the main complications, hypercoagulability, which predisposes dogs to disseminated intravascular coagulation and pulmonary thromboembolism, is the most important and leading cause of death in more than 80% of cases. Primary IMHA cannot be associated with an obvious predisposition, besides breed predilection, because of this it is a diagnostic exclusion. Secondary IMHA is related to several agents, and among the infectious ones, ehrlichiosis stands out. Animal selection for this study was based on hematological, biochemical, and urine tests. Dogs with moderate to severe anemia (hematocrit ≤ 25%), with symptoms of immune-mediated hemolysis, such as spherocytosis, positive saline agglutination, bilirubinuria and/or hemoglobinuria, were included. The treatment is directed towards immune response suppression, for which glucocorticoids and mycophenolate mofetil are frequently used. This study aimed to clarify whether the thrombotic risk changes after the initiation of immunosuppressive therapy with mycophenolate mofetil, through thromboelastometry, in animals with primary IMHA and secondary to E. canis infection. The animals under study were submitted to hemogram, reticulocyte count, spherocytosis screening, serum biochemistry, urinalysis, urinary protein/creatinine ratio, coagulation tests, thromboelastometry; PCR for E. sp, E. canis and B. canis; serology for Leptospira spp and abdominal ultrasonography. Twelve dogs with a diagnosis of IMHA were selected and a thromboelastic examination was performed at two moments: before the start of treatment with mycophenolate mofetila, when the patient used doxycycline, omeprazole and prednisolone (M1) and after the addition of mycophenolate mofetila to the protocol mentioned above, when there was clinical and hematological improvement (M2). Five animals died before moment 2. The Willcox nonparametric test was used to compare the two moments of the surviving group, and the nonparametric Mann-Whitney test was used to compare the moment 1 of the surviving group with the death group, both with 5% significance value. No change in the coagulation state of animals treated with mycophenolate mofetil was observed. The animals that showed lower coagulation at the time of diagnosis exhibited a worse prognosis, and the reticulocyte count showed a better prognostic value than the red blood cell count at the time of diagnosis
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Palavras-chave
AHIM, E. canis, hemostasia, hipercoagulabilidade, tromboelastometria