School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil
Cancer has many effects on the veterinary patients. Particular attention should be given to the paraneoplastic syndromes. Paraneoplastic changes are those that occur in the organism in a distant location from the primary tumor and can be the first indication of cancer in some animals. The early identification of these alterations allows rapid diagnosis of the primary process and start the procedures for the treatment. Then, many paraneoplastic diseases disappear when tumor remission is achieved.
Hematologic abnormalities are very common paraneoplastic syndromes seen in the veterinary patients. Changes in any cell line are possible. Probably anemia is the most important. There are few researches about hematologic abnormalities in veterinary medicine when compared to human medicine. In a large survey in 2004 when more than 15,000 cancer patients were studied, 31% showed anemia at the diagnosis, and 53% of patient with hematologic malignancies were anemic. In human beings, anemia has been showed as an independent prognostic factor for survival in lung carcinoma, head and neck carcinoma, prostate carcinoma, lymphoma and multiple myeloma. In these cases, the presence of anemia increases the risk for death by 65%. In veterinary medicine, anemia affects approximately 30% of the dogs.
Several types of anemia are associated with neoplasia and the degree may vary from mild to severe. The underlying etiopathogenesis in cancer veterinary patients in not fully understood but can be related to chronic disease, blood loss, immune-mediated hemolysis, chronic antineoplastic treatment and pure red cell aplasia (uncommon). Anemia of chronic disease seems to be the main problem and the pathogenesis is multifactorial, as a result of decreased iron availability, shortened erythrocyte life span and decreased erythropoiesis. This kind of anemia is characterized as a mild to moderate in degree and normocytic, normochromic, although in some dogs microcytosis may be observed. There is no specific treatment and the control is to address to the primary tumor.
Blood loss can be observed in several bleeding tumors such as skin tumors, hemangiosarcoma, urinary, gastrointestinal and nasal tumors, because the tumor vasculature is abnormal and more fragile. Anemia is generally microcytic, hypochromic, regenerative or nonregenerative. The treatment of choice is the control of the primary tumor.
Immune mediated hemolytic anemia often is diagnosed by the presence of spherocytes in blood smears and the regenerative characteristics. Many animals may present jaundice. In these cases, even with treatment of the cancer, immune suppression with prednisone alone or in association with another immunosuppressive drugs may be necessary.
Animals without anemia by the time of cancer diagnosis, can present it during antineoplastic treatment. Anemia is often mild, normocytic, normochromic, nonregenerative and is associated with a long-term chemotherapy. Serial evaluation of the complete blood count before each chemotherapeutic treatment is necessary to evaluate any gradual decline.
Although the treatment of anemia must be addressed to the underlying cause, very often blood transfusions are necessary when the packed cell volume is close to 12% or less. It is a palliative treatment while waiting for other cancer treatment to take effect, as well as the use of erythropoietin. Erythropoietin can be beneficial because it helps to downregulate the factors activated by the hypoxia. Until homologous erythropoietin becomes available for veterinary patients, the risk of its use should be analyzed for each individual patient.
Regarding to hematologic malignancies, actually anemia is considered as a negative prognostic factor for dogs with lymphoma undergoing chemotherapy. There is an association between moderate anemia and decreased survival time in canine lymphoma.
The mechanism by which anemia may contribute to decrease the response to the treatment and survival time is unclear. Chronic hypoxia can induce the expression of factors such as vascular endothelial growth factor, that is a negative prognostic factor in dogs with lymphoma and also contributes to the decreased the efficacy of some chemotherapeutic drugs and the development of acquired drug resistance. The control of anemia is essential because it compromise the quality of life, that is the major considerations to euthanasia decision by the owners.
Thrombocytopenia is another abnormality commonly seen with neoplasia (up to 40% of the dogs) mainly dogs with lymphoma. Possible causes for the thrombocytopenia are the decreased of platelet life span due to accelerated removal from the circulation, associated to the microaggregation stimulated by the tumor, or coating of the platelets by tumor proteins, beyond the binding to abnormal endothelium in blood vessels. Besides that, the production of anti-platelets antibody by the tumor and the cross reactivity between tumor antigens and platelet antigens also can lead to thrombocytopenia.
Concerning to white blood cells, when animals show a remarkable degree of leukocytosis without any obvious focus of infection or possibility of leukemia, paraneoplastic syndrome should be suspect, with granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating, interleukin 3 (IL-3) and interleukin 6 (IL-6) production. These cytokines enhance the production of granulocytes and their release from bone marrow into the peripheral blood. This reaction have been described mainly in association with lung, gastrointestinal, genitourinary tumors and lymphoma.
Finally, although eosinophilic paraneoplastic syndrome is considered a marker for systemic or intestinal mast cell neoplasia, it was also reported in cats with intestinal lymphoma. In humans this abnormality, secondary to T cell lymphoma, is common and the mechanism of eosinophil recruitment is the production of IL-5 from neoplastic lymphocytes.
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