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Feline Health Topics for Veterinarians

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Feline Health Topics for veterinarians Winter 1991 Volume 6, Number 1 Anemia in Cats (Part II) Julia T. Blue, D.V.M., Ph.D. Editor’s Note: This segment of the two-part series rare complication in hyperthyroid cats treated with discusses hemolytic and complex anemias in the cat. propylthiouracil (PTU). Severe anemia and thrombocytopenia have been seen in less than 10% of Hemolytic Anemias cats treated with PTU. Most affected cats recover if Autoimmune Hemolytic Anemia. Spontaneously the drug is stopped and they are treated with supportive occurring autoimmune hemolytic anemia is much and immunosuppressive therapy. more rare in cats than in dogs. Some cases thought to Neonatal Isoerythrolysis. Blood type A kittens be autoimmune hemolytic anemia are probably bom to type B queens can die of acute intravascular hemobartonellosis. Moderate to severe anemia with hemolytic anemia caused by anti-A alloantibodies reticulocytosis and a positive Coombs’ test are ingested in colostrum. Sensitization of the queen by indicative of autoimmune hemolytic anemia. The previous pregnancy or transfusion is not necessary mean corpuscular volume (MCV) is high in many for the disease to occur. cases. Because autoimmune hemolytic anemia can be secondary to other infectious or neoplastic diseases, Heinz Body Hemolytic Anemia. Oxidant agents and can be a component of systemic immune mediated affect erythrocytes in several ways. The clinical disease (i.e. systemic lupus erythrematosis), thorough manifestation of oxidant injury depends on the degree examination of the cat is recommended. and nature of the changes. Oxidation of the iron of hemoglobin— normally in the ferrous state— to ferric Drug-induced Immune Mediated Hemolytic iron produces methemoglobin, which is not capable Anemia. Coombs’ positive hemolytic anemia is a of oxygen transport. Oxidation of exposed sulfhydryl groups on hemoglobin causes formation of disulfide bonds and distortion of the tertiary structure of the hemoglobin molecule. The result is precipitation of Inside this issue... hemoglobin. Precipitated hemoglobin coalesces to Anemia in Cats (Part n) page 1 form the intracellular inclusions called Heinz bodies. Extensive Heinz body formation and attachment of The Cat's Meow page 5 Heinz bodies to the membrane increase the rigidity of Subject Index page 6 the erythrocytes and render them susceptible to fragmentation and entrapment in the spleen where Meetings page 8 they are phagocytized. Oxidation of membrane proteins can cross-link areas of the membrane, likewise decreasing erythrocyte deformability Feline Health Topics 2 (increasing rigidity). Hemolytic anemiaresulting from Small, nonpathologic Heinz bodies can be found oxidant injury to erythrocytes is called Heinz body in blood of most cats whether nonanemic or anemic hemolytic anemia. due to other reasons. These small Heinz bodies in nonanemic cats have been called erythrocyte refractile Erythrocytes contain several systems to protect bodies because they appear as shiny red to purple their components from the oxidants (e.g. superoxide inclusions when a drop of blood-new methylene blue anion and hydrogen peroxide) produced during nor­ mixture is examined with a microscope. The presence mal metabolism. An enzyme called NADH- of nonpathologic Heinz bodies in cats can be attributed methemoglobin reductase uses NADH produced by to the increased susceptibility of cat hemoglobin to glycolysis to maintain hemoglobin iron in the ferrous oxidative denaturation compared to other species and state by reducing the small amount of methemoglobin the structure of the cat spleen which makes it inefficient produced normally. Glutathione peroxidase degrades at pitting out small inclusions from erythrocytes. hydrogen peroxide and in the process reduced Therefore, anemia in a cat should not be attributed to glutathione (GSH) is oxidized to GSSG (oxidized oxidant injury unless Heinz bodies are large and glutathione). GSH is maintained by de novo synthesis erythrocyte shape abnormalities are evident in the and by reduction of GSSG in a reaction involving routinely stained smear. Additionally, a reticulocytosis glutathione reductase and NADPH produced in the should be present. pentose phosphate pathway. Defects in the protective mechanisms or exposure to agents that overcome the protective systems can produce methemoglobinemia and/or hemolytic anemia. Because cat hemoglobin has more exposed serum hepatitis groups than the hemoglobin of other species, cats are especially susceptible to Heinz body formation. Feline Health Topics Extravascular hemolysis is predominant in many cases of Heinz body hemolytic anemia, but A publication for veterinary professionals intravascular hemolysis can occur if membrane The ultimate purpose of the Cornell Feline Health Center is to damage is severe (dependent on both dose and agent). improve the health of cats everywhere, by developing methods to prevent or cure feline diseases, and by providing continuing The degree of anemia varies from subclinically mild education to veterinarians and cat owners. All contributions are to very severe. Reticulocytosis and macrocytosis are tax-deductible. D irector: Fredric W. Scott, D.V.M., Ph.D. usual if the anemia is severe. Depending on the agent Assistant Director: John E. Saidla, D.V.M. Editor: June E. Tuttle producing the oxidant injury, methemoglobinemia Secretaries: Sheryl A. Thomas, Gwen Frost, Julie Elzer can accompany the hemolytic anemia. Some oxidant agents produce methemoglobinemia as the predom­ This publication is made possible, in part, by a grant from 9-Lives Cat Foods. We grate­ inant form of erythrocyte injury, with Heinz body fully acknowledge this interest and support in the furthering of feline health. This formation and hemolytic anemia only a minor acknowledgement of our gratitude is not an endorsement of any particular company or component of the disorder. product. © 1991 by C ornell U niversity on behalf of the Clinical signs of high methemoglobin concen­ Cornell Feline Health Center, College of tration are cyanosis, dyspnea, and weakness. Because Veterinary Medicine, Ithaca, NY 14853. All rights reserved. Permission to reprint se­ of the decreased oxygen content, blood with high lected portions must be obtained in writing. Cornell University is an equal opportunity, methemoglobin concentration appears dark and affirmative action educator and employer. brown; normal color is not restored by exposing the Printed on recycled paper. CP233 blood to air. 3 Compounds that cause Heinz body hemolytic anemia: Propylene glycol, a preservative used in soft- Reported cases in cats had both extravascular and moist pet foods, is capable of producing Heinz intravascular hemolysis. body hemolytic anemia when fed in amounts found in commercial foods. Higher doses produce a greater DL-methionine, which is administered to cats to effect. The anemia is mild and essentially prevent signs of feline urologic syndrome (FUS), can subclinical. produce Heinz body hemolytic anemia and methem­ oglobinemia at doses greater than 0.5 g/kg/day. Severity Acetaminophen and ph enacetin produce of the changes is dose related. Unidentified metabolites severe and often fatal disease in cats. The syn­ of methionine are thought to be the toxic compounds. drome is associated with both intravascular and extravascular hemolysis and methemoglobinemia. Benzocaine, a topical anesthetic, can produce severe Signs include vomiting, icterus, anorexia, cyanosis, methemoglobinemia in cats in a dose-related manner. facial edema, hemoglobinuria, and sometimes Heinz bodies are not produced. Cetacaine, a benzocaine- convulsions. containing spray for anesthetizing the larynx prior to intubation, should not be used in cats. Toxic met­ N-acetylcysteine given via nasogastric tube at hemoglobinemia with signs of cyanosis, dyspnea and an initial dose of 140 mg/kg followed by 70 mg/kg vomiting was reported in a cat within 20 minutes of administered orally every six hours for 36 hours is application of an over-the-counter skin cream (Lanacane) an effective treatment if administered within to puritic areas by the owner. approximately 24 hours of ingestion of the drug. A dose as small as two 325 mg tablets of acet­ Onions, probably the most common cause of Heinz aminophen can cause severe illness in a cat. body hemolytic anemia in dogs, also can cause anemia Methylene blue, which is sometimes used to treat in cats if ingested in sufficient quantity. toxic methemoglobinemia in other species, should not be given to cats because it enhances the Heinz Endogenous oxidants, of unknown nature, are body formation and increases the severity of the considered to be the cause of Heinz body hemolytic anemia. anemia in some cats that have no known exposure to exogenous agents. Diabetes mellitus, lymphoma, and Phenazopyridine, a urinary tract analgesic, is hyperthyroidism are several diseases in which another drug that should not be administered to concurrent Heinz body hemolytic anemia, presumably cats because it produces Heinz body hemolytic due to endogenous oxidants, has been recognized. anemia, methemoglobinemia, and hepatic injury. Complex Anemias Therefore, appropriate diagnosis and management of Many cats with moderate to severe, apparently anemic cats should be based on consideration of all nonregenerative anemias have multiple contri­ possible factors. buting causes. For example, a cat with traumatic blood loss anemia may not have an increased Anemia Due to Bone Marrow Neoplasia reticulocyte count until post-trauma inflammation
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