Primary immune-mediated hemolytic anemia (IMHA) is an important cause of serious morbidity and mortality in dogs. Despite numerous studies examining the demographics, treatment options, and prognostic indicators of disease, the mechanisms that underlie immune dysregulation remain poorly understood. The purpose of this study was to directly identify unique erythrocyte membrane antigens in dogs diagnosed with primary IMHA. Blood samples were obtained from dogs presented to the Ontario Veterinary College Teaching Hospital with primary IMHA prior to treatment, and also from control dogs (healthy dogs and dogs with non-immunologic anemia). Antibodies bound to erythrocyte membranes were eluted using xylene. Immunoblots using patient eluates reacted against pooled canine erythrocyte lysates, and autologous patient plasma reacted against xylene eluates, were performed. These results were compared to results of similar experiments using samples from control dogs. Bands appearing in patient but not control samples were considered potential autoantigens, and were submitted for identification by liquid chromatography followed by tandem mass spectrometry. Samples from 13 dogs with primary IMHA, 4 dogs with non-immunologic anemia, and 2 healthy dogs, were analyzed. Immunoblotting confirmed the presence of immunoglobulin in eluates from all dogs. Semi-quantitatively, eluates from IMHA patients contained more immunoglobulin than those of control dogs. Mass spectrometry identified complement C3 in patient but not in control dog samples. Additional peptides identified by mass spectrometry in patient but not control dog samples included peroxiredoxin 2 and calpain. The former comprises a cytosolic hydrogen peroxide scavenger, and has been associated with erythrocyte membranes under oxidative stress conditions inducing spherocytosis. Calpain is a calcium-dependent protease that may become activated with oxidative stress and induce erythrocyte apoptosis. These findings suggest that oxidative stress and apoptosis contribute to the pathogenesis of canine IMHA. / OVC Pet Trust Fund, American Kennel Club Canine Health Foundation

Thrombotic microangiopathies (TMA) are disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microthrombi leading to organ dysfunction. Atypical hemolytic uremic syndrome (aHUS) is a rare subtype of TMA mediated by complement dysregulation. We present a case of a 59-year-old female who presented with acute kidney injury and mild thrombocytopenia but with normal hemoglobin. We highlight the importance of prompt diagnosis of aHUS and initiating appropriate treatment with eculizumab.

A piometra é uma condição mórbida caracterizada pela inflamação do útero com acúmulo de exsudatos, resultante de ações hormonais e geralmente associada à presença de bactérias no lúmen uterino. A anemia é a alteração hematológica mais frequentemente observada em cadelas com piometra e está associada à cronicidade da doença, diminuição da eritropoiese, devido ao efeito toxêmico na medula óssea, diminuição da disponibilidade de ferro ou perda de sangue para o útero. Adicionalmente, o efeito das toxinas bacterianas e os radicais livres gerados pelo metabolismo oxidativo dos neutrófilos podem resultar na modificação da estrutura antigênica da membrana do eritrócito, permitindo a ligação de imunoglobulinas em sua superfície e acelerando a destruição eritrocitária. Essa hipótese pode ser comprovada pela detecção de imunocomplexos na superfície eritrocitária de cadelas com piometra. O diagnóstico de piometra foi estabelecido em 33 cadelas atendidas no Serviço de Obstetrícia/Ginecologia do Hospital Veterinário da Universidade de São Paulo com base na anamnese, exame físico e exames subsidiários (ultrassonografia, hemograma e concentrações séricas de ureia e creatinina). As amostras sanguíneas foram coletadas em dois momentos. A primeira anterior a ovariosalpingohisterectomia (OSH) e a segunda, sete a dez dias após a OSH. A quantificação de hemácias com deposição de imunocomplexos IgG e IgM foi realizada utilizando-se anticorpos anti-IgG e anti-IgM (Bethyl®Laboratories) conjugadas a fluoresceína de isotiocianato (FITC), e a leitura realizada com citômetro de fluxo (FACS Calibur; Becton, Dickinson and Company© 2007 BD), sendo os resultados expressos em percentual de hemácias marcadas. Foram utilizados o Teste de Shapiro-Wilk para a avaliação da distribuição de dados e a comparação entre os grupos controle, pré e pós-OSH foi realizada valendo-se do Teste t ou Teste t pareado e Correlação de Pearson, e do Teste U de Mann-Whitney e Correlação de Spearman, para as variáveis com distribuição normal e não-normal, respectivamente. O valor de alfa estipulado foi de 0,05. Analisando os valores hematológicos de cada um dos cães incluídos no estudo, observa-se que 19 (57,6%) apresentavam anemia normocítica normocrômica não regenerativa no momento pré-OSH e cinco (15,2%) no momento pós-OSH. Em cães do grupo controle foram observadas 0,14 - 0,77% (0,43±0,18%) de hemácias marcadas com anticorpos anti-IgG FITC e 0,29 - 9,58% (0,68±0,29%) para anticorpos anti-IgM FITC. Já nos cães com piometra, foram encontradas 0,14 - 4,19% (0,96±0,86%) de hemácias marcadas com anticorpos anti-IgG FITC e 0,29 - 9,58% (1,37±1,71%) com anticorpos anti-IgM FITC, antecedendo a OSH. No momento pós-OSH observou-se 0,18 - 16,2% (2,77±3,67%) de hemácias marcadas para anticorpos anti-IgG FITC e 0,15 - 19,8% (4,01±4,46%) para anticorpos anti-IgM FITC. O percentual de hemácias marcadas com anticorpos anti-IgG FITC diferiu entre os grupos controle e piometra, pré-OSH (p<0,001) e pós-OSH (p<0,001). Em relação a anticorpos anti-IgM FITC, não foram observadas diferenças entre os grupos controle e pré-OSH (p=0,09), porém, após a OSH houve aumento na marcação de hemácias, quando comparado ao grupo controle (p<0,001). Apenas alguns animais apresentaram mais de 5% de hemácias marcadas, e isto ocorreu, principalmente, no momento pós-OSH. Entretanto, não resultou no agravamento da anemia, indicando que a piometra em cadelas está associada à deposição de imunoglobulinas G ou M na superfície das hemácias, sem, no entanto, promover hemólise ou agravamento da anemia / The pyometra is a morbid condition characterized by inflammation of the uterus with exudates accumulation resulting from hormonal action and usually associated with the presence of bacteria in the uterine lumen. Anemia is the hematologic changes most frequently observed in bitches with pyometra and is associated with chronic disease, diminished erythropoiesis due to toxemic effect on the bone marrow, decreased iron availability or loss of blood to the uterus. Additionally, the effect of bacterial toxins and free radicals generated by neutrophil oxidative metabolism may result in the modification of antigenic structure of the erythrocyte membrane, allowing the binding of immunoglobulins on their surface and accelerating erythrocyte destruction. This hypothesis can be confirmed by detection of immune complexes in the erythrocyte surface dogs with pyometra. The diagnosis of pyometra was established in 33 dogs attended by the Obstetrics Service/Gynecology of Veterinary Hospital of the University of São Paulo based on history, physical examination and additional tests (ultrasound, blood count and serum concentrations of urea and creatinine). Blood samples were collected in two stages. The first prior to ovariohysterectomy (OSH) and the second, seven to ten days after OSH. Quantification of erythrocyte with deposition of IgG and IgM immune complexes was performed using antibodies anti-IgG and anti-IgM (Bethyl® Laboratories) conjugated to fluorescein isothiocyanate (FITC), and the reading performed with flow cytometry (FACS Calibur; Becton, Dickinson and Company© 2007 BD), and the results expressed as a percentage of red blood cells marked. The Shapiro-Wilk test was used to assess the distribution of data and the comparison between the control group, pre- and post-OSH was carried out making use of the t test or paired t test and Pearson correlation, and test U Mann-Whitney and Spearman correlation for the variables with normal and non-normal distribution, respectively. The stipulated alpha value was 0.05. The analysis of the hematological values of each of the dogs enrolled in the study, it was observed that 19 (57.6%) with anemia normocytic normochromic non-regenerative in the pre-OSH moment and 5 (15.2%) in the post-OSH moment. In control group of dogs were observed from 0.14 to 0.77% (0.43± 0.18%) of red blood cells marked with antibodies anti-IgG FITC and 0.29 to 9.58% (0.68± 0.29%) for antibodies anti-IgM FITC. Already in dogs with pyometra were found 0.14 to 4.19% (0.96 ± 0.86%) of red blood cells marked with antibodies anti-IgG FITC and 0.29 to 9.58% (1.37 ± 1.71%) with antibodies anti-IgM FITC, prior to OSH. In the post-OSH time it was observed 0.18 to 16.2% (2.77 ± 3.67%) of red blood cells marked for antibodies anti-IgG FITC and 0.15 to 19.8% (4.01 ± 4.46%) for antibodies anti-IgM FITC. The percentage of red blood cells marked with antibodies anti-IgG FITC differ between groups control and pyometra, pre-OSH (p<0.001) and post-OSH (p<0.001). Regarding the antibodies anti-IgM FITC, no differences were observed between the control and pre-OSH (p=0.09), however, after the OSH was no increase in labeling of red blood cells compared to the control group (p<0.001). Only a few animals have more than 5% of marked red blood cells, and this was mainly in the post-OSH time. However, not result in the worsening of anemia, indicating that pyometra in dogs is related to the deposition of immunoglobulin G or M on the surface of erythrocytes, without, however, promote hemolysis or worsening of anemia

[Truncated abstract] Iron is a trace mineral used by the body in many physiological processes that are essential to athletic performance. Commonly, the body's iron stores are compromised by exercise via several well established mechanisms. One such mechanism is the destruction of red blood cells (hemolysis), in response to the mechanical stress and circulatory strain of exercise. Although it appears that a force-dependent relationship between the heel-strike of the running gait and ground contact exists, the effects of the intensity trained at and the ground surface type trained upon have not been documented. Similarly, the effects of a cumulative training stress (i.e. multiple daily sessions) has not been examined. In addition to hemolysis, exercise also invokes an inflammatory response that results in an up-regulation of the cytokine interleukin-6 (IL-6). This cytokine is the primary mediator of hepcidin expression, a liver-produced hormone that regulates iron metabolism in the gut and in macrophages. The influence of exercise on hepcidin expression is relatively unknown, and as such it is possible that this hormone may be a mitigating factor implicated in athletic-induced iron deficiency. Therefore, the purpose of this thesis was to investigate the effect of different training frequencies, intensities and ground surfaces on the hemolytic response. In addition, the impact of exercise-induced inflammation on hepcidin expression in the 24 h post-exercise was investigated, with the aim of determining whether this hormone may be a potential new mechanism associated with athletic-induced iron deficiency. Finally, an interaction between hemolysis and hepcidin activity was examined to investigate their potential combined effect on iron status in the 24 h post-exercise. ... Venous blood and urine samples were collected pre- and immediately post-exercise, and at 3 and 24 h of recovery. Samples were analysed for circulating levels of IL-6, free Hb, Hp, serum iron, ferritin and urinary hepcidin activity. At the conclusion of both the T1 and T2 interval runs, the free Hb and serum Hp were significantly increased (p<0.05) from pre-exercise levels. Furthermore, a cumulative effect of two running sessions was shown in the T2 trial, via a further significant fall in serum Hp. The IL-6 and hepcidin activity were significantly increased after each running session (p<0.05) with no cumulative effect seen. Serum iron and ferritin were significantly increased post-exercise after each interval run (p<0.05), but were not influenced by the addition of a prior LSD run 12 h earlier. As a result, this investigation showed a cumulative effect of consecutive training sessions on RBC destruction in male athletes. Furthermore, post-exercise increases to serum iron and hepcidin, and their interaction was suggested to have potential implications for an athlete's iron status. Overall, the findings of this thesis show that hemolysis is evident at the conclusion of endurance running, and is influenced by training intensity and frequency. The results enabled a time-line for hepcidin expression post-exercise to be established, and the implications of increases to the activity of this hormone, in association with the hemolytic changes seen with endurance exercise are discussed.

A piometra é uma condição mórbida caracterizada pela inflamação do útero com acúmulo de exsudatos, resultante de ações hormonais e geralmente associada à presença de bactérias no lúmen uterino. A anemia é a alteração hematológica mais frequentemente observada em cadelas com piometra e está associada à cronicidade da doença, diminuição da eritropoiese, devido ao efeito toxêmico na medula óssea, diminuição da disponibilidade de ferro ou perda de sangue para o útero. Adicionalmente, o efeito das toxinas bacterianas e os radicais livres gerados pelo metabolismo oxidativo dos neutrófilos podem resultar na modificação da estrutura antigênica da membrana do eritrócito, permitindo a ligação de imunoglobulinas em sua superfície e acelerando a destruição eritrocitária. Essa hipótese pode ser comprovada pela detecção de imunocomplexos na superfície eritrocitária de cadelas com piometra. O diagnóstico de piometra foi estabelecido em 33 cadelas atendidas no Serviço de Obstetrícia/Ginecologia do Hospital Veterinário da Universidade de São Paulo com base na anamnese, exame físico e exames subsidiários (ultrassonografia, hemograma e concentrações séricas de ureia e creatinina). As amostras sanguíneas foram coletadas em dois momentos. A primeira anterior a ovariosalpingohisterectomia (OSH) e a segunda, sete a dez dias após a OSH. A quantificação de hemácias com deposição de imunocomplexos IgG e IgM foi realizada utilizando-se anticorpos anti-IgG e anti-IgM (Bethyl&reg;Laboratories) conjugadas a fluoresceína de isotiocianato (FITC), e a leitura realizada com citômetro de fluxo (FACS Calibur; Becton, Dickinson and Company&copy; 2007 BD), sendo os resultados expressos em percentual de hemácias marcadas. Foram utilizados o Teste de Shapiro-Wilk para a avaliação da distribuição de dados e a comparação entre os grupos controle, pré e pós-OSH foi realizada valendo-se do Teste t ou Teste t pareado e Correlação de Pearson, e do Teste U de Mann-Whitney e Correlação de Spearman, para as variáveis com distribuição normal e não-normal, respectivamente. O valor de alfa estipulado foi de 0,05. Analisando os valores hematológicos de cada um dos cães incluídos no estudo, observa-se que 19 (57,6%) apresentavam anemia normocítica normocrômica não regenerativa no momento pré-OSH e cinco (15,2%) no momento pós-OSH. Em cães do grupo controle foram observadas 0,14 - 0,77% (0,43&#177;0,18%) de hemácias marcadas com anticorpos anti-IgG FITC e 0,29 - 9,58% (0,68&#177;0,29%) para anticorpos anti-IgM FITC. Já nos cães com piometra, foram encontradas 0,14 - 4,19% (0,96&#177;0,86%) de hemácias marcadas com anticorpos anti-IgG FITC e 0,29 - 9,58% (1,37&#177;1,71%) com anticorpos anti-IgM FITC, antecedendo a OSH. No momento pós-OSH observou-se 0,18 - 16,2% (2,77&#177;3,67%) de hemácias marcadas para anticorpos anti-IgG FITC e 0,15 - 19,8% (4,01&#177;4,46%) para anticorpos anti-IgM FITC. O percentual de hemácias marcadas com anticorpos anti-IgG FITC diferiu entre os grupos controle e piometra, pré-OSH (p&lt;0,001) e pós-OSH (p&lt;0,001). Em relação a anticorpos anti-IgM FITC, não foram observadas diferenças entre os grupos controle e pré-OSH (p&#61;0,09), porém, após a OSH houve aumento na marcação de hemácias, quando comparado ao grupo controle (p&lt;0,001). Apenas alguns animais apresentaram mais de 5% de hemácias marcadas, e isto ocorreu, principalmente, no momento pós-OSH. Entretanto, não resultou no agravamento da anemia, indicando que a piometra em cadelas está associada à deposição de imunoglobulinas G ou M na superfície das hemácias, sem, no entanto, promover hemólise ou agravamento da anemia / The pyometra is a morbid condition characterized by inflammation of the uterus with exudates accumulation resulting from hormonal action and usually associated with the presence of bacteria in the uterine lumen. Anemia is the hematologic changes most frequently observed in bitches with pyometra and is associated with chronic disease, diminished erythropoiesis due to toxemic effect on the bone marrow, decreased iron availability or loss of blood to the uterus. Additionally, the effect of bacterial toxins and free radicals generated by neutrophil oxidative metabolism may result in the modification of antigenic structure of the erythrocyte membrane, allowing the binding of immunoglobulins on their surface and accelerating erythrocyte destruction. This hypothesis can be confirmed by detection of immune complexes in the erythrocyte surface dogs with pyometra. The diagnosis of pyometra was established in 33 dogs attended by the Obstetrics Service/Gynecology of Veterinary Hospital of the University of São Paulo based on history, physical examination and additional tests (ultrasound, blood count and serum concentrations of urea and creatinine). Blood samples were collected in two stages. The first prior to ovariohysterectomy (OSH) and the second, seven to ten days after OSH. Quantification of erythrocyte with deposition of IgG and IgM immune complexes was performed using antibodies anti-IgG and anti-IgM (Bethyl&reg; Laboratories) conjugated to fluorescein isothiocyanate (FITC), and the reading performed with flow cytometry (FACS Calibur; Becton, Dickinson and Company&copy; 2007 BD), and the results expressed as a percentage of red blood cells marked. The Shapiro-Wilk test was used to assess the distribution of data and the comparison between the control group, pre- and post-OSH was carried out making use of the t test or paired t test and Pearson correlation, and test U Mann-Whitney and Spearman correlation for the variables with normal and non-normal distribution, respectively. The stipulated alpha value was 0.05. The analysis of the hematological values of each of the dogs enrolled in the study, it was observed that 19 (57.6%) with anemia normocytic normochromic non-regenerative in the pre-OSH moment and 5 (15.2%) in the post-OSH moment. In control group of dogs were observed from 0.14 to 0.77% (0.43&plusmn; 0.18%) of red blood cells marked with antibodies anti-IgG FITC and 0.29 to 9.58% (0.68&#177; 0.29%) for antibodies anti-IgM FITC. Already in dogs with pyometra were found 0.14 to 4.19% (0.96 &#177; 0.86%) of red blood cells marked with antibodies anti-IgG FITC and 0.29 to 9.58% (1.37 &#177; 1.71%) with antibodies anti-IgM FITC, prior to OSH. In the post-OSH time it was observed 0.18 to 16.2% (2.77 &#177; 3.67%) of red blood cells marked for antibodies anti-IgG FITC and 0.15 to 19.8% (4.01 &#177; 4.46%) for antibodies anti-IgM FITC. The percentage of red blood cells marked with antibodies anti-IgG FITC differ between groups control and pyometra, pre-OSH (p&lt;0.001) and post-OSH (p&lt;0.001). Regarding the antibodies anti-IgM FITC, no differences were observed between the control and pre-OSH (p&#61;0.09), however, after the OSH was no increase in labeling of red blood cells compared to the control group (p&lt;0.001). Only a few animals have more than 5% of marked red blood cells, and this was mainly in the post-OSH time. However, not result in the worsening of anemia, indicating that pyometra in dogs is related to the deposition of immunoglobulin G or M on the surface of erythrocytes, without, however, promote hemolysis or worsening of anemia

Made available in DSpace on 2014-06-11T19:27:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-11Bitstream added on 2014-06-13T19:14:30Z : No. of bitstreams: 1 moraes_lf_me_botfmvz.pdf: 428197 bytes, checksum: bc0cb7abb11b1fca9cd1b81b73ec75e5 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A anemia hemolítica imuno-mediada (AHIM) é a causa mais comum das anemias hemolíticas e tem sido associada a estados de hipercoagulabilidade. Neste trabalho objetivou-se: avaliar a ocorrência de alterações hematológicas, hemostáticas e renais e a prevalência das classes de imunoglobulinas (Ig) envolvidas nas AHIM. 87 cães anêmicos foram submetidos ao teste de Coomb’s, citometria de fluxo (CF) e auto-aglutinação, além de hemograma e contagem de reticulócitos, perfil hemostático e renal, pesquisa de hematozoários e testados para Ehrlichia sp e leptospirose. Os resultados foram analisados pelo teste t, Mann-Whitney ou Kruskal-Wallis ao nível de 5% de significância. 61 cães (70,11%) foram positivos para AHIM na CF, 31 (35,63%) para o Coomb’s e 24 (27,58%) para auto-aglutinação. Não houve predomínio de uma classe de Ig envolvida. As alterações clínico-laboratoriais para cães com AHIM incluíram anemia regenerativa, macrocítica, hipocrômica e reticulocitose, além de icterícia, febre, hiperglobulinemia e bilirrubinúria. 9,8% dos cães positivos apresentaram esferocitose, 29,5% leucocitose, 39,6% neutrofilia e 72,1% trombocitopenia. A proteinúria e o aumento na relação proteína: creatinina urinárias revelam indícios de lesão renal. Os cães anêmicos positivos e negativos para AHIM apresentaram diferença estatística em relação ao grupo controle para contagem de plaquetas, TP, TTPA, AT, PDF e Dímeros D. 25 cães positivos e sete cães negativos para AHIM apresentaram um estado tromboembólico. Estas alterações hemostáticas podem ser atribuídas à causa base predominante para a anemia em questão, uma vez que 74,6% dos casos de AHIM foram atribuídos às doenças infecciosas, a maioria associados à Ehrlichia sp / Immune-mediated hemolytic anemia (IMHA) is the most common cause of hemolytic anemia and has been associated with hypercoagulable states. The objectives of this study were: to evaluate the incidence of hemostatic, renal and hematological abnormalities, and the prevalence immunoglobulin’s classes involved in IMHA. 87 anemic dogs were selected and submitted to Coomb’s test, flow cytometry (FC) and auto-agglutination, along with CBC, reticulocyte count, hemostatic and renal profile, hemoparasite search in peripheral blood smears, and Ehrlichia sp and leptospirosis tests. The results were analyzed by t test, Mann-Whitney or Kruskal-Wallis at 5% of significance. 61 dogs (70.11%) were positive to IMHA by CF, 31 (35.63%) by Coomb's test and 24 (27.58%) by auto-agglutination. There wasn’t a predominance of IgG or IgM involvement. The hematological and clinical changes in dogs with IMHA included macrocytic, hypochromic regenerative anemia, and reticulocytosis, as well as icterus, fever, auto-agglutination, hyperglobulinemia and bilirubinuria. 9.8% of dogs with IMHA had spherocytosis, 29.5% leukocytosis, 39.6% neutrophilia and 72.1% thrombocytopenia. Proteinuria and the increase in urine protein creatinine ratio reveal evidences of renal injury. There were statistical differences between the control group and anemic dogs positive or negative for IHMA to the following tests: platelet count, PT, APTT, AT, FDP and D-dimer. 25 positive dogs and seven negative dogs for IMHA were in a thromboembolic state. These hemostatic changes observed in both groups of anemic dogs may be attributed to the predominant underlying cause of anemia, since 74.6% of IHMA cases were attributed to infectious diseases; mostly Ehrlichia sp related

Orientador: Regina Kiomi Takahira / Banca: Raimundo Souza Lopes / Banca: Áureo Evangelista Santana / Resumo: A anemia hemolítica imuno-mediada (AHIM) é a causa mais comum das anemias hemolíticas e tem sido associada a estados de hipercoagulabilidade. Neste trabalho objetivou-se: avaliar a ocorrência de alterações hematológicas, hemostáticas e renais e a prevalência das classes de imunoglobulinas (Ig) envolvidas nas AHIM. 87 cães anêmicos foram submetidos ao teste de Coomb's, citometria de fluxo (CF) e auto-aglutinação, além de hemograma e contagem de reticulócitos, perfil hemostático e renal, pesquisa de hematozoários e testados para Ehrlichia sp e leptospirose. Os resultados foram analisados pelo teste t, Mann-Whitney ou Kruskal-Wallis ao nível de 5% de significância. 61 cães (70,11%) foram positivos para AHIM na CF, 31 (35,63%) para o Coomb's e 24 (27,58%) para auto-aglutinação. Não houve predomínio de uma classe de Ig envolvida. As alterações clínico-laboratoriais para cães com AHIM incluíram anemia regenerativa, macrocítica, hipocrômica e reticulocitose, além de icterícia, febre, hiperglobulinemia e bilirrubinúria. 9,8% dos cães positivos apresentaram esferocitose, 29,5% leucocitose, 39,6% neutrofilia e 72,1% trombocitopenia. A proteinúria e o aumento na relação proteína: creatinina urinárias revelam indícios de lesão renal. Os cães anêmicos positivos e negativos para AHIM apresentaram diferença estatística em relação ao grupo controle para contagem de plaquetas, TP, TTPA, AT, PDF e Dímeros D. 25 cães positivos e sete cães negativos para AHIM apresentaram um estado tromboembólico. Estas alterações hemostáticas podem ser atribuídas à causa base predominante para a anemia em questão, uma vez que 74,6% dos casos de AHIM foram atribuídos às doenças infecciosas, a maioria associados à Ehrlichia sp / Abstract: Immune-mediated hemolytic anemia (IMHA) is the most common cause of hemolytic anemia and has been associated with hypercoagulable states. The objectives of this study were: to evaluate the incidence of hemostatic, renal and hematological abnormalities, and the prevalence immunoglobulin's classes involved in IMHA. 87 anemic dogs were selected and submitted to Coomb's test, flow cytometry (FC) and auto-agglutination, along with CBC, reticulocyte count, hemostatic and renal profile, hemoparasite search in peripheral blood smears, and Ehrlichia sp and leptospirosis tests. The results were analyzed by t test, Mann-Whitney or Kruskal-Wallis at 5% of significance. 61 dogs (70.11%) were positive to IMHA by CF, 31 (35.63%) by Coomb's test and 24 (27.58%) by auto-agglutination. There wasn't a predominance of IgG or IgM involvement. The hematological and clinical changes in dogs with IMHA included macrocytic, hypochromic regenerative anemia, and reticulocytosis, as well as icterus, fever, auto-agglutination, hyperglobulinemia and bilirubinuria. 9.8% of dogs with IMHA had spherocytosis, 29.5% leukocytosis, 39.6% neutrophilia and 72.1% thrombocytopenia. Proteinuria and the increase in urine protein creatinine ratio reveal evidences of renal injury. There were statistical differences between the control group and anemic dogs positive or negative for IHMA to the following tests: platelet count, PT, APTT, AT, FDP and D-dimer. 25 positive dogs and seven negative dogs for IMHA were in a thromboembolic state. These hemostatic changes observed in both groups of anemic dogs may be attributed to the predominant underlying cause of anemia, since 74.6% of IHMA cases were attributed to infectious diseases; mostly Ehrlichia sp related / Mestre

Autoimmune hemolytic anemia (AIHA) is a disease process that involves the destruction of red blood cells mediated by the humoral immune system. It can be characterized as a cold agglutinin syndrome, paroxysmal cold hemoglobinuria, and warm, mixed type, and drug-induced AIHA. Although a well-established relationship exists between the presence of AIHA and lymphoproliferative malignancy, AIHA rarely presents in association with solid malignancies. An analysis of the limited number of published cases of AIHA in association with solid malignancies performed showed that AIHA may present before the diagnosis of a solid malignancy, concurrently with the presence of a solid malignancy, or even on resolution of a solid malignancy. Few cases of solid cancers associated with AIHA have been reported. AIHA rarely presents as a paraneoplastic syndrome indicating existence of a solid cancer. We report a case of inflammatory breast cancer with AIHA.

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Oil spills have long been recognized as a significant threat to wildlife. Historically, mortality estimates have served as the basis for assessing impact to natural resources. However, these mortality estimates alone neglect the more wide-spread impact of oil spills on wildlife including birds, many of which may not immediately succumb to exposure, but instead suffer sublethal injury that may negatively affect physiological homeostasis, reproduction, and long-term survival. Therefore, there is a need to improve our understanding of the risk of exposure and effect of sublethal oiling during damage assessments. In this dissertation I evaluated the extent of sublethal oil exposure in the immediate aftermath of the Deepwater Horizon spill on American oystercatchers (Haematopus palliatus), black skimmers (Rynchops niger), brown pelicans (Pelecanus occidentalis), clapper rails (Rallus crepitans), and seaside sparrows (Ammodramus maritimus) through both visual evaluation of and under the application of ultraviolet light to individual birds potentially exposed to oil. I found that there were many individual birds with modest oil exposure, demonstrating that more birds are exposed to oil than are accounted for by mortality estimates. Additionally, I developed a field-adapted technique using an in vitro method in brown pelicans that was effective in determining oxidative hematologic injury as measured by a suite of parameters including a reduction in circulating erythrocytes and hemoglobin, formation of Heinz bodies, and an increase in reticulocytes, in birds exposed to oil. I then applied this suite of parameters to individual birds affected in the aftermath of the Deepwater Horizon spill, and found that birds with modest visible or UV-detectible oil exposure suffer hematologic injury, a quantifiable adverse sublethal effect of modest oil exposure. Finally, I used an experimental approach to evaluate the pathologic effects of crude oil exposure in zebra finches (Taeniopygia guttata), evaluating the same suite of hematologic parameters as well as gross pathology, histopathology, and electron microscopy. This controlled study provided evidence that there may be significant variability in the response of birds to oil exposure that may be attributable to species-specific sensitivity and/or other factors such as the use of dispersants after oil spills. Collectively, this body of work demonstrated that many more birds are exposed to oil during spill events than are accounted for by mortality estimates alone, and that these birds can suffer quantifiable sublethal hematologic injury. The ability to accurately assess the extent of exposure and hematologic damage caused by oil spills is critical to determine the appropriate approach to management needed to offset impacts to fisheries, wildlife, habitats, and economic resources impacted by oil spills. / Doctor of Philosophy / Fossil fuels are the world's primary energy source and are an important part of everyday life. Our reliance on petroleum requires extraction, transportation, storage, and refinement of millions of gallons of crude oil each day. As an unintended consequence, some of this oil is inadvertently spilled into the environment, and these oil spills have long been recognized as a threat to wildlife. Assessing the impact of oil spills on wildlife is a major concern to industries, government, and the general public. Historically, mortality estimates have served as the basis for assessing impact to natural resources. However, these mortality estimates alone neglect the more wide-spread impact of oil spills on wildlife including birds, many of which may not immediately succumb to exposure, but instead suffer sublethal physiologic injury that negatively affects physiology, reproduction, and long-term survival. Therefore, there is a need to improve our understanding of the risk of exposure and effects of sublethal oiling during damage assessments. In this dissertation, I evaluated the extent of sublethal exposure to oil from The Deepwater Horizon spill for several species of birds through both visual evaluation of and under the application of ultraviolet light. This demonstrated that many more birds are affected by oil exposure than are accounted for by mortality estimates. Additionally, I developed a field-adapted technique in a controlled setting that is effective in determining oxidative injury to red blood cells in birds exposed to oil, and applied this approach to several species in the field during the aftermath of the Deepwater Horizon spill. Finally, I used an experimental approach to evaluate the extent of pathologic effects of Deepwater Horizon crude oil exposure in individuals under controlled dosages. The ability to accurately assess the extent of damage caused by oil spills is critical to determine the appropriate approach to management needed to offset impacts to fisheries, wildlife, habitats, and economic resources impacted by oil spills.