Prognosis in canine idiopathic immune-mediated haemolytic anaemia

Canine idiopathic immune-mediated haemolytic anaemia (iIMHA) is one of the most frequently occurring immune-mediated diseases in dogs. A gel-based Coombs' test was shown to perform equally well as a classical Coombs' test. Since the gel-based Coombs' test can be commercially produced and is easy and fast to perform, this offers the opportunity to standardize anti-erythrocyte antibody testing. Two retrospective cohorts of dogs with iIMHA were studied; one cohort was treated with prednisolone and azathioprine (n=149), and the other cohort (n=73) was treated with prednisolone only. Dogs of both cohorts presented with severe anaemia, leukocytosis, and a third of the dogs had increased coagulation times and thrombocytopenia. There was no significant difference in survival between the two protocol groups; the one year survival times were 64% (95% CI 54-77%) for the group treated with prednisolone, and 69% for the group treated with prednisolone and azathioprine, respectively. It can be concluded that, contrary to current belief, the addition of azathioprine to a protocol of prednisolone does not decrease mortality. Azathioprine causes bone marrow suppression, however, in 8% of dogs. Contrary to current recommendations for lifelong immunosuppresion, a duration of immunosuppression for 3 months was sufficient to maintain remission of the haemolytic anaemia in both protocol groups. Almost all mortality occurred in the first 2 weeks after diagnosis. Multivariate Cox's proportional hazards analysis showed that main predictors of this mortality were the presence of icterus, increases in plasma urea and creatinine, a left shift, increases in coagulation times, and thrombocytopenia. Since leucocytes have been shown to express tissue factor, it was hypothesized that leucocytes taking part in the inflammatory response in dogs with iIMHA had increased expression of interleukin-8 and tissue factor. Nine commonly used reference genes were examined for their suitability as reference genes in canine whole blood. It was shown that the leukocyte count affected the expression of these reference genes. This emphasized that commonly used reference genes may not be stable under all experimental conditions and the assumption of stable expression under all conditions should be checked for each new experiment. The basal interleukin-8 and tissue factor expression were determined in healthy dogs. These expressions were compared with the expression of dogs with sepsis, dogs with disseminated intravascular coagulation, and dogs with iIMHA. Dogs with systemic illness and dogs that had surgery but did not have sepsis or DIC, were included as controls. Since patient care related issues such as intravenous catheters may change tissue factor and interleukin-8 expressions as well. The dogs with iIHA had a pronounced leukocytosis with left shift and signs of hypercoagulability. The coagulation factor activities were low and platelet parameters suggested platelet activation and high platelet turnover. Tissue factor expression was high in the dogs with iIMHA, but the interleukin-8 expression was low. Since both tissue factor and interleukin-8 result from activation of the NF-kB signaling pathway this suggests that the tissue factor expression is not increased in leucocytes, but possibly in other blood cells. A possible role for thrombocytes should be investigated

Evaluation of the results of a L-asparaginase-based continuous chemotherapy protocol versus a short doxorubicin-based induction chemotherapy protocol in dogs with malignant lymphoma.

The results of an L‐asparaginase‐based continuous chemotherapy protocol (n = 52) versus a short doxorubicin‐based induction chemotherapy protocol (n = 65) were evaluated in 117 dogs with malignant lymphoma. There were no differences between the two groups in patient characteristics or incidence of protocol‐related toxicity. Complete remission was induced in 71.2% of the dogs treated with the Lasparaginase protocol and in 67.7% of the dogs treated with the doxorubicin‐plus protocol. The calculated Kaplan‐Meier one‐ and two‐year survival fractions in the L‐asparaginase group were 48% and 26%, and in the doxorubicin‐plus group 35%, and 22%, respectively. Differences in remission and survival between the two treatment groups were not significant. A multivariate Cox proportional hazards survival analysis revealed that elevated pretreatment plasma creatinine concentration and prior treatment with prednisolone were associated with shorter survival times. An elevated pretreatment plasma creatinine concentration and total leucocyte count were associated with a decrease in the disease‐free period. Differences in efficacy and toxicity between the two protocols were not significant. There is no apparent advantage in using the continuous L‐asparaginase protocol, and the shorter doxorubicin‐plus protocol is less expensive and less time consuming

Evaluation of the results of a L-asparaginase-based continuous chemotherapy protocol versus a short doxorubicin-based induction chemotherapy protocol in dogs with malignant lymphoma.

The results of an L‐asparaginase‐based continuous chemotherapy protocol (n = 52) versus a short doxorubicin‐based induction chemotherapy protocol (n = 65) were evaluated in 117 dogs with malignant lymphoma. There were no differences between the two groups in patient characteristics or incidence of protocol‐related toxicity. Complete remission was induced in 71.2% of the dogs treated with the Lasparaginase protocol and in 67.7% of the dogs treated with the doxorubicin‐plus protocol. The calculated Kaplan‐Meier one‐ and two‐year survival fractions in the L‐asparaginase group were 48% and 26%, and in the doxorubicin‐plus group 35%, and 22%, respectively. Differences in remission and survival between the two treatment groups were not significant. A multivariate Cox proportional hazards survival analysis revealed that elevated pretreatment plasma creatinine concentration and prior treatment with prednisolone were associated with shorter survival times. An elevated pretreatment plasma creatinine concentration and total leucocyte count were associated with a decrease in the disease‐free period. Differences in efficacy and toxicity between the two protocols were not significant. There is no apparent advantage in using the continuous L‐asparaginase protocol, and the shorter doxorubicin‐plus protocol is less expensive and less time consuming

Apoptosis of haematopoietic cells can be induced with an antibody against tomoregulin-1.

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High intravascular tissue factor expression in dogs with idiopathic immune-mediated haemolytic anaemia

A high mortality occurs in dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this study was to investigate the inflammatory response and coagulation abnormalities in dogs with IMHA in relation to the prognosis and to establish the contribution of whole blood tissue factor (IF) and IL-8 gene expressions. Gene expressions in dogs with IMHA were compared to healthy dogs, dogs with DIC, dogs with sepsis, and in two groups of dogs that underwent intensive care treatment but had no evidence for either DIC or sepsis. The whole blood TF and IL-8 expressions were up regulated in all non-IMHA groups. Similarly, the TF expression in IMHA dogs was high, but the intravascular IL-8 expression was not increased. The dogs with IMHA had a pronounced inflammatory response that included a high WBC, left shift and monocytosis in comparison to the other disease groups. Coagulation factor activities in IMHA dogs were decreased fitting consumptive coagulopathy and the acute phase proteins FVIII and fibrinogen were increased. The platelet parameters suggested platelet activation and high platelet turnover in IMHA dogs. The model that best explained mortality contained monocytosis, increased activated partial thromboplastin time and elevated creatinine. Whole blood TF gene expression is up regulated and may contribute to consumptive coagulopathy in dogs with IMHA. Increased TF expression by activated platelets is an alternative explanation and should be investigated

Induction of apoptosis in hematopoietic cells with an antibody against tomoregulin-1.

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