Anemia in Feline Critical Illness

Douglass K. Macintire, DVM, MS, DACVIM, DACVECC
Auburn University
Auburn, AL, USA

citation

Anemia is common in critically ill cats. The origin may be either acute or chronic. The diagnostic workup for cats with acute anemia should include the following: evaluation of blood smear, slide agglutination test, complete blood count, new methylene blue stain for Heinz bodies, Coomb's test, blood typing, FeLV/FIV testing, chemistry panel, coagulation testing (if evidence of bleeding) and PCR for hemotropic mycoplasmas.

Causes of acute anemia include hemorrhage or hemolysis. Cats are more likely to develop anemia following blood loss than dogs because they have a reduced blood volume (60 ml/kg vs. 90 ml/kg). In addition, cats are more at risk for toxic anemias because they are predisposed to Heinz body anemia because of extra sulfhydril groups on feline hemoglobin that are prone to oxidative injury.

Parasitic Anemias: Blood smears from anemic cats should be evaluated for red blood cell parasites. Mycoplasma hemofelis (formerly hemobartonella felis) causes a regenerative hemolytic anemia that is usually positive on the direct antiglobulin test. The organisms appear as chains of small cocci on the red blood cell surface. Treatment involves doxycycline 10 mg/kg PO q 24 h for 14-21 days. Prednisone 2 mg/kg PO q 12 h can be given for 2 weeks and then tapered off gradually in cats that do not respond to antibiotics alone. An alternate treatment is enrofloxacin 5mg/kg PO for 14 days. Azithromycin is ineffective. Cats often become subclinical carriers following treatment, and stress may cause reoccurrence of disease. Two other hemotropic mycoplasmas have recently been discovered through PCR testing. A small blood parasite, Candidatus mycoplasma, hemominutum, has been found in 20-50% of cats in California, but has not been associated with anemia or clinical signs. A third parasite, Mycoplasma turicensis has been found in cats worldwide and appears to be slightly more pathogenic than M. hemominutum. The best method for diagnosis of hemotropic mycoplasmas is PCR testing before antibiotics. Co-infection with FeLV and FIV is common. Blood donor cats should be negative for all hemotropic mycoplasmas.

Cytauxzoonosis occurs in endemic areas of the southern USA where bobcats are the suspected host. It is transmitted to cats by blood sucking insects. Large shizonts form in the spleen and bone marrow. Merozoites are released from the shizonts and parasitize red blood cells 24-48 h prior to death. The organisms appear in RBC’s as bipolar "safety pins" or "signet rings". Clinical signs include icterus, fever, hepatosplenomegaly, collapse, and death. If treated early, survival has been reported with imidocarb (5 mg/kg IM twice 14 days apart), along with supportive care including IV fluids and blood transfusion. The earliest diagnosis is made from finding schizonts in lymph node, splenic or bone marrow aspirates. Recently, Birkenheuer treated 22 cats with 15 mg/kg atovaquone PO q 12 h and 10 mg/kg azithromycin PO q 24 h for 14 days and 14 cats survived. This treatment is more effective than imidocarb in achieving survival, reduction in numbers of piroplasms, and obtaining negative PCR status.

Toxic anemias are caused by oxidants such as zinc, acetaminophen, local anesthetics, new methylene blue, propofol, propylene glycol, and onion powder in baby food. Acetaminophen causes methemoglobinemia as well as Heinz body anemia. Classic signs include brown colored blood, "muddy" mucous membranes, facial edema, tachypnea, and weakness. Treatment includes 5% acetylcysteine (140mg/kg PO or IV, followed by 70 mg/kg q 6 hours until resolution of clinical signs - usually 7 treatments). Ascorbic acid is given as an antioxidant at a dosage of 30 mg/kg POq 6 h. Supportive care with oxygen and intravenous fluids may be needed.

Primary immune mediated hemolytic anemia is rare in cats, so secondary causes such as FeLV, FIV, blood parasites, and drugs should be ruled out. Abyssinians and Somalis are known to have hereditary defects (PK deficiency and increased osmotic fragility) that can cause hemolytic anemia, and genetic testing should be considered in these breeds. Pure red cell aplasia and myelodysplastic syndrome sometimes respond to immunosuppressive therapy and may be variants of immune mediated disease. Cats with IMHA rarely develop pulmonary thromboembolism, and may have a better prognosis than dogs if they are negative for FeLV and FIV. Immunosuppressive drugs used in cats include prednisolone (2-4 mg/kg/day PO), cyclosporine (5 mg/kg PO q 12 h), chlorambucil (0.1-0.2 mg/kg PO q 24 h), and mycofenolate mofitil (10 m/kg PO q 12 h). Azathioprine cannot be used in cats.

Hypophosphatemia may cause hemolytic anemia in cats with diabetes, hepatic lipidosis, or malnutrition when nutrition is reintroduced. After starvation, when carbohydrates are given, phosphorus is consumed in the production of ATP and enzymes in the glycolysis pathway, resulting in hypophosphatemia. Reduced phosphorus can lead to hemolytic anemia, muscle weakness, and is often evidenced by very high CPK values in affected cats. The recommended dose for phosphate replacement is 0.01-0.06 mmol/kg/h IV for 6-12 hours. Potassium phosphate solutions contain 3 mmol/ml phosphate and 4.3 mEq/ml potassium. The best way to prevent hypophosphatemia from "refeeding syndrome" is to reintroduce food gradually to malnourished patients, beginning with 25-30% of their resting energy requirement and gradually increasing to the full caloric requirement over 3-4 days.

Causes of chronic non-regenerative anemia include feline leukemia, feline immunodeficiency virus, myelodysplasia, infiltrative neoplasia, chronic blood loss, chronic renal failure or anemia of chronic disease. Diagnostic testing should be performed to rule out FeLV and FIV in all anemic cats. Additional work-up should include complete blood count, serum chemistries and urinalysis to rule out extramarrow disease such as chronic infection, liver disease or renal disease. Bone marrow evaluation is generally indicated in cases of pancytopenia or non-regenerative anemia with no evidence of extra-marrow disease.

Nonspecific treatment of chronic non-regenerative anemia involves the use of anabolic steroids (Anadrol-50, Winstrol-V, Deca-Durabolin). It may take a month for any effect to be seen, and the efficacy of these agents is questionable. The most effective drug is thought to be Deca-Durabolin at a dosage of 1-5 mg/kg IM weekly. Erythropoeitin can be used in cats that have normal RBC precursors in the bone marrow. The dosage is 100 U/kg SC 3 times weekly until the hematocrit reaches 30% at which time the frequency is reduced to 1-2 times weekly. This treatment is often effective in cats with anemia secondary to chronic renal disease. Ferrous sulfate (10 mg/kg PO SID) should be given concurrently. A serious side effect of this therapy is that human erythropoetin can induce antierythropoetin antibodies that can make an animal transfusion dependent. Therefore, its use should be reserved for cats that have a reduced quality of life because of anemia.

Administration of chloramphenicol has been associated with non-regenerative anemia in cats. Any drugs that are potential causes of bone marrow suppression should be discontinued in anemic cats.

Cats with chronic blood loss anemia secondary to internal or external parasites, gastrointestinal bleeding or urinary losses will require iron supplementation (50-100 mg/day PO - Ferrous sulfate).

Transfusion Medicine

It is now possible to obtain cat blood from veterinary blood banks, but many practices draw fresh whole blood when needed from a donor cat. Feline blood donors should be domestic shorthaired cats > 8 lbs that are negative for FeLV, FIV, Mycoplasma spp, and toxoplasmosis. Cats can safely donate up to 14 ml/kg once a month. Donor cats are sedated with a ketamine:valium mixture (50:50 mixture, 0.1 ml/kg IV) and blood is aseptically collected through a 19 g butterfly catheter into 5-6 10 ml syringes each containing 1-1.5 ml CPD-A anticoagulant. The blood can be administered through a syringe pump over 4 hours. The amount of blood needed can be determined by the following formula:

BW (kg) x 70 x PCVdesired - PCVrecipient
PCVdonor

Most DSH cats in the United States have type A blood. Breeds likely to have type B blood include Devon Rex, Cornish Rex, Scottish Fold, British Shorthair, Norwegian Forest Cat, Persian, Himalayan, Abyssinian, Birman, Sphinx, and Somali. All cats, especially, exotic breeds and purebreds should be typed with a card test (DMS laboratories, Flemington, NJ) before transfusion. An immediate, severe, life-threatening reaction can occur if a type B cat is given type A blood. If this occurs, the transfusion should be discontinued immediately and treatment instituted for anaphylactic shock. Blood should always be administered through a blood filter to remove fibrin clots and platelet aggregates. Blood products, filters, anticoagulants, etc. can be obtained from any of the following animal blood banks: Animal Blood Bank (Vacaville, CA), Eastern Veterinary Blood Bank (Annapolis, MD), Hemopet (Irvine, CA), Midwest Animal Bloodbank Services, Inc (Stockbridge, MI), and Penn Animal Blood Bank (Philadelphia, PA). The life span of a normal transfused RBC is 21-48 days in the cat.

 

Neonatal isoerythrolyis occurs in type A kittens that have ingested colostrum from a type B queen. The colostrum contains antibodies that cause lysis of the kittens' red blood cells. Clinical signs include anemia, icterus, darkly pigmented urine, "fading kitten syndrome", or sudden death within the first week of life. Supportive care includes a transfusion of type B blood (20 ml/kg IV or IO over 2 h), external warming, IV or SC fluids, and nutrition. Nursing can be resumed after 24 hours because colostrum is no longer absorbed through the GI tract. All breeding pairs of suspect breeds should be typed to avoid mating type B queen with type A males.

 

Kohn B, Weingart C, Eckmann V, et al. Primary immune-mediated hemolytic anemia in 19 cats: diagnosis, therapy, and outcome (1998-2004). J Vet Intern Med 2006; 20:159-166.
Birkenheuer AJ, Le SA, Valenzisi, et al. Cytauxzoon felis in cats in the mid-Atlantic states: 34 cases (1998-2004). J Am Vet Med Assoc 2006; 228(4):568-576.
Castellano SI, Couto CG, Gray TL. Clinical use of blood products in cats: A retrospective study (1997-2000). J Vet Intern Med 2004;18:529-532.
Birkenheuer AJ, Cohn LA, Levy MG, et al. Atovaquone and azithromycin for the treatment of Cytauxzoon felis. Conference Proceedings, ACVIM 2008, Abstract #13.
Macintire, DK, Drobatz KJ, Haskins SC, Saxon WD. Manual of Small Animal Emergency and Critical Care Medicine. Ames, IA: Blackwell Publishing, 2005; pp. 279-295.

 

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