Iron Deficiency in Dogs and Cats

pattyPatty 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

Transient iron deficiency anemia (IDA) in neonates on all milk diet
Blood sucking parasites
Intestinal bleeding (tumors, ulcers etc) or intestinal malabsorption
Chronic kidney disease
Urinary bleeding (bladder tumors)
Hemorrhagic disorders (diathesis, coagulopathy)
Latrogenic (blood donors)

Table 2. Features of Severe Iron Deficiency Anemia in Dogs

Parameter Finding
Serum iron Decreased
Total Iron Binding Capacity (TIBC) Normal
Ferritin Decreased
Transferrin saturation <20%
Hematocrit (HCT) Low
Mean Corpuscular Volume (MCV) Decreased
Mean Corpuscular Hbcontent (MCHC) Decreased
Red Blood Cell (RBC) morphology Hypochromasia, microcytosis and RBC fragmentation
Red cell distribution width (RDW) Increased anisocytosis
Platelets Thrombocytosis (increased platelet count).
Chemistry panel Low total protein related to concomitant intestinal losses of albumin and globulin.

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

Product Route Dose Comments
Iron dextran 50 mg/ml IM Cats: adjunct to EPO treatment: 50 mg IM every 3-4 weeksDogs: 10-20 mg/kg IM once and continue treatment with oral ferrous sulfate A small dose should be injected IM to test for hypersensitivity reaction. A maximal dose of 2 mls is administered daily.
Ferrous sulfate PO Cats: 50 – 100 mg/cat/day

Dogs: 100-300/dog/day

Exists in 2 forms (regular and dried). Doses are given for regular ferrous sulfate and not for elemental  iron.A dose of 300 mgs of iron sulfate provides 60 mg of elemental iron.Side effects: anorexia, vomiting.If bad GI side effects develop it is recommended to give IM Fe dextran
Ferrous gluconate PO A dose of 325 mg of iron gluconate provides 36 mgs of elemental iron.
Pet-tinic® (Pfizer animal health) PO Contains 12.5 mg of iron per 1 tablespoon. For adequate iron supplementation at time of iron deficiency a cat will need to ingest 4-8 tablespoons of the liquid per day (which is not realistic)
Vitamin C PO Dogs: 500-1000 mg per dayCats: 125 mgs BID Can be used to increase GI absorption of oral iron. Side effects may include GI disturbances and increased risk for urate, oxalate and cystine stone formation

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