Iron Deficiency in Dogs and Cats

Patty Ewing, DVM, MS, DACVP (Anatomic and Clinical Pathology)
www.angell.org/lab
pathology@angell.org
617 541-5014

Introduction – Iron deficiency in dogs

At Angell Animal Medical Center, the majority of cases of iron deficiency anemia are due to chronic hemorrhage from gastrointestinal tumors. Diagnosis of uncomplicated and chronic iron deficiency is based on classic hematologic and biochemical abnormalities such as changes in erythrocyte indices (microcytic, hypochromic anemia) and decreased serum ferritin concentration (table 2). Detection of early iron deficiency, before the appearance of those abnormalities, or iron deficiency in the presence of other diseases (e.g., neoplasia and inflammation) is a diagnostic challenge.^4,5 In uncomplicated iron deficiency, the serum iron concentration and ferritin are typically low and the TIBC (total iron binding capacity) is usually high. Because iron is preferentially shunted to hemoglobin (Hb) formation, typical hematologic changes do not occur until late in iron deficiency, long after detrimental effects have occurred. Also, serum ferritin is an acute phase reactant and concentrations may be increased with certain neoplastic and inflammatory diseases, which may make diagnosis of concurrent iron deficiency challenging. Although the immunologic assay for canine serum ferritin has been available for over a decade, its value in detecting iron deficiency anemia (IDA) in chronically ill dogs is not reported. Many clinicians consider the evaluation of bone marrow aspirates or biopsies for the presence or absence of stainable iron as a sensitive and reliable test for iron status assessment in dogs. However, some hematologists consider this invasive procedure to be subjective and imprecise. Thus, the true prevalence of iron deficiency may be unknown, and dogs with early iron deficiency masked by concurrent disease may remain undiagnosed and untreated. Accurate diagnosis of early or complicated iron deficiency is made more difficult by the highly variable results obtained for biochemical markers of iron in serum; including serum iron (Fe) concentration, TIBC, and percent saturation of transferrin. Serum Fe concentration is affected by several factors such as time of day, corticosteroid administration, and consumption of meat.⁴  Reticulocyte indices may be helpful in evaluating for possible causes of anemia.  Fry et al demonstrated that reticulocyte indices differed by greater than 3-fold between healthy dogs and dogs with IDA.⁵  Steinberg et al demonstrated that low mean Hb content of reticulocytes and low reticulocyte MCV are associated with hematologic and serum biochemical abnormalities indicative of iron deficiency.⁴  Both these indices hold promise as non invasive, cost effective measures of iron status assessment in dogs.⁴ Further determination of normal reference ranges for reticulocyte indices and comparison between those indices and other causes of regenerative anemias are indicated before it is available for clinical use. Small intestinal malabsorption can also promote IDA. Iron deficiency anemia secondary to inflammatory bowel disease (IBD) has been reported in dogs; therefore, determination of serum iron, ferritin, and TIBC may be worthwhile in anemic dogs with IBD.⁶  In one study, serum iron concentrations in 3 of 6 dogs and 3 of 7 cats with chronic renal failure (CRF) were below the reference interval (transferrin saturation less than 20%).⁷ Whether this is related primarily to inadequate intake and absorption of iron or increased losses of iron due to GI blood loss is unclear.⁷  It is important to distinguish anemia secondary to iron deficiency from anemia of inflammation since only iron deficiency should be supplemented with iron. When erythropoietin (EPO) therapy is used in CRF patients, the demand for iron during stimulated erythropoiesis is high; therefore, iron supplementation is recommended for patients receiving EPO.⁸

Iron deficiency in cats – Treatment

Transfusion of red blood cells (whole blood or packed red blood cells) should be considered for patients with IDA clinical for anemia.¹ The patient hematocrit should be raised to 15-20%. The goal of calculating the transfusion volume is avoid reaching a higher hematocrit that will dampen the bone marrow erythrocyte production (table 3).¹²

The first line of therapy for iron deficiency anemia is parenteral iron administration. Iron preparations administered intravenously may cause anaphylactic reactions, thus the intramuscularly (IM) route is preferred.¹³ A small dose should be injected IM to test for hypersensitivity reactions. A maximal dose of 2 mls can be administered daily.¹⁴ Large doses of injectable iron may discolor the serum brown which can cause falsely elevated serum bilirubin values and falsely decrease serum calcium values.¹³ Iron deficiency in dogs is addressed first by administering iron dextran once at 10-20 mg/kg IM and then continuing therapy with oral iron. In cats the dose for prevention of transient iron deficiency anemia in kittens is 50 mg of iron dextran IM at 18 days of age. The dose for adjunctive therapy with EPO treatment is 50 mg of iron dextran IM every 3 to 4 weeks or daily oral supplementation. Oral iron therapy usually follows injectable iron (the first line therapy for patients with IDA) (table 4). Oral iron absorption varies widely based on the type of diet and other factors. Sustained release iron formulations are not recommended as initial therapy because they reduce the amount of iron that is presented for the absorption by the duodenal villi.¹ Gastrointestinal absorption of elemental iron is enhanced in the presence of an acidic gastric environment. This can be accomplished through concurrent intake of ascorbic acid (Vitamin C).^{1, 13} Most common side effects of oral iron supplementation are gastrointestinal upset (mostly vomiting) and constipation. Division of the daily dose may reduce gastrointestinal upset. Although iron absorption occurs more readily when taken on an empty stomach, this increases the likelihood of stomach upset.¹ Oral iron may result in black discoloration of feces and cause false positive reactions with the guaiac occult blood test.¹³ A common product used for iron supplementation is Pet-Tinic (Pfizer Animal Health). It contains 12.5 mg of iron per tablespoon. For adequate iron supplementation at time of iron deficiency, a cat will need to ingest 4 – 8 tablespoons of the liquid per day. Many cats will not tolerate oral supplementation, thus injections of iron dextran may be required in some cases.¹³

Conclusion

Chronic blood loss from bleeding gastrointestinal tumors and intestinal parasitism are the most common causes of iron deficiency. Early recognition and treatment of iron deficiency can prevent life threatening anemia. IDA must be differentiated from anemia of chronic disease so that appropriate treatment can be initiated.

For more information about iron deficiency, please contact Angell’s Pathology service at 617-541-5041 or pathology@angell.org.

Table 1. Causes of iron deficiency in dogs and cats

Table 2. Features of Severe Iron Deficiency Anemia in Dogs

Table 3. Calculation of approximate volume of blood required to raise hematocrit levels.

Table 4. Iron products for treatment of iron deficiency in dogs and cats

References:

1. Killip S, Bennet JM, Chambers MD. Iron deficiency anemia. American Family Physician 2007;75:671-678.
2. Smith JE. Iron metabolism and its diseases, in Kaneko JJ, eds. In: Clinical Biochemistry of Domestic Animals, Fourth edition. Academic Press 1989:256-273.
3. Neumann S. Serum iron level as an indicator for inflammation in dogs and cats. Comp Clin Path 2003;12:90-94.
4. Steinberg JD, Olver CS. Hematologic and biochemical abnormalities indicating iron deficiency are associated with decreased reticulocyte hemoglobin content (CHr) and reticulocyte volume in dogs. Vet Clin Path 2006;34(1): 23-27.
5. Fry MM, Kirk CA. Reticulocyte indices in a canine model of nutritional iron deficiency. Vet Clin Path 2006;35(2):172-181.
6. Ristic JME, Stidworthy MF. Two cases of iron-deficiency anaemia due to inflammatory bowel disease in the dog. Journal of Small Animal Practice 2002;43:80-83.
7. Cowgil LD, James KM, Levy JK et al. Use of recombinant human erythropoietin for management of anemia in dogs and cats with renal failure, JAVMA 1998;212 (4):521-528.
8. Polzin JD. Chronic kidney disease. In: Ettinger JS, Feldman EC, eds. Textbook of Veterinary Internal Medicine.  St Louis: Elsevier Saunders; 2005;1781-1783.
9. Willard MD. Erythrocyte disorders. In: Willard MD, Tvedten H, eds. Small animal clinical diagnosis by laboratory methods. W. B. Saunders Company;2004:53-54
10. Andrews GA, Chavey PS, Smith JE. Enzyme-linked immunosorbent assay to measure serum ferritin and the relationship between serum ferritin and nonheme iron stores in cats. Veterinary Pathology 1994;31:674-678.
11. Fulton R, Weiser MG, Freshman JL et al. Electronic and morphologic characterization of erythrocytes of an adult cat with iron deficiency anemia. Veterinary Pathology 1988;25:521-523.
12. Bistner SI, Ford RB, Raffe MR. Blood component therapy. In: Kirk and Bistner’s Handbook of veterinary procedures and emergency treatment, 7^th W.B SaundersCompnay 2000; 571-582.
13. Plumb DC. Plumb’s Veterinary Drug Handbook, Fifth Edition Blackwell Publishing 2005
14. Giger U. Regenerative anemias caused by blood loss or hemolysis. In: Ettinger JS and Feldman EC, eds. Textbook of Veterinary Internal Medicine, 6^th St. Louis: Elsevier Saunders; 2005:1886-1890.