Anemia

Problem Definition

Anemia is defined as a decrease in the erythrocyte mass below the laboratory reference interval, usually as measured by the packed cell volume (PCV). The hematocrit is a similar measure of erythrocyte mass, but is a value provided by hematology analyzers that is calculated from the measured red blood cell (RBC) count and mean cell volume (MCV). The PCV, RBC count, and hemoglobin (Hgb) concentration usually decrease proportionally. Individual laboratory reference intervals may differ slightly, but typically a PCV less than 37% in dogs and 27% in cats is considered anemic.

Pathophysiology

Anemia can result in decreased oxygenation of tissues, with resultant clinical signs of lethargy, exercise intolerance, tachypnea, tachycardia, and sometimes collapse. Mucous membranes appear pale. Severe anemia may result in a systolic heart murmur due to decreased blood viscosity. The severity of clinical signs is affected by how fast the anemia develops; acute anemia will result in more severe clinical signs than an anemia of the same magnitude that develops slowly. Anemia is caused by one of three basic mechanisms: blood loss (hemorrhage), red blood cell destruction (hemolysis), or decreased red blood cell production in the bone marrow. These mechanisms are not mutually exclusive, and more than one may be operating in any individual patient. The apparent red blood cell mass is affected by hydration status; dehydration may mask an anemia, while overhydration will decrease the PCV and total protein and mimic a blood loss anemia.

Initial Diagnostic Plan

Determining if the anemia is regenerative is a useful first step to shorten the list of differential diagnoses (see Table 54-1).

Regenerative anemias are expected in cases of hemorrhage or hemolysis, provided enough time has elapsed for the bone marrow to increase red blood cell production and start releasing reticulocytes (usually at least2–3 days). A regenerative anemia is defined by increased numbers of reticulocytes, and is best detected by obtaining the absolute number of reticulocytes per microliter (|J.L) of blood. A reticulocyte count greater than 60,000/μL in dogs or 50,000/μL in cats indicates a regenerative anemia. The absolute number can be determined manually by obtaining a reticulocyte percentage (using new methylene blue to stain red blood cells in suspension and then preparing a blood film) and multiplying that percentage by the total RBC count per microliter. Only aggregate reticulocytes (not punctuate) are counted in cats. In the absence of an RBC count the reticulocyte percentage (retic%) must be corrected for the degree of anemia, since a larger percentage of reticulocytes is required to give the same absolute number of reticulocytes as the RBC count progressively decreases. The formula for a corrected reticulocyte percentage is as follows: reported retic% × (patient’s reported PCV/patient’s normal PCV) = corrected retic%. Normal PCV values commonly used for dogs and cats are 45 and 37%, respectively. A corrected reticulocyte percentage more than 1% in dogs or more than 0.4% in cats suggests a regenerative anemia. Examples of the significance of reticulocyte counts for dogs and cats are given in Table 54-2. Finding marked polychromasia on a Wright’s stained blood film suggests regeneration, but is less sensitive than a reticulocyte count. Other blood film findings that often accompany a regenerative response include Howell–Jolly bodies, nucleated RBCs, and occasionally basophilic stippling; however, these are not specific for a regenerative response. Because reticulocytes are larger and contain less Hgb than mature RBCs, the MCV may be slightly increased and the mean cell hemoglobin concentration (MCHC) may be slightly decreased whenever there is a marked regenerative response.

TABLE 54-1. Causes of anemia

FeLV, feline leukemia virus; DIC, disseminated intravascular coagulation; PK, pyruvate kinase; PFK, phosphofructokinase.

* May be nonregenerative if directed against RBC precursors.

^† Nonregenerative anemia more common.

TABLE 54-2. Interpretation of regenerative responses on the basis of absolute numbers of reticulocytes

Once a regenerative anemia has been confirmed, additional tests should be directed at differentiating hemolysis from hemorrhage. Plasma protein concentrations may be useful, as loss of whole blood results in loss of both albumin and globulin. Thus, a regenerative anemia with low total protein (both albumin and globulin) supports hemorrhage as the underlying cause. Conversely, total protein is frequently normal in cases of hemolysis. Blood loss may be external or internal; body excretions (feces, urine, vomitus) as well as body cavities should be evaluated for evidence of hemorrhage. The patient should be checked for endoor exoparasitism. Patients with hemorrhage may require evaluation of platelet numbers and function or coagulation testing. Cases of chronic hemorrhage may not have decreased total protein since the liver’s synthetic capability can often keep up with slow protein losses. Chronic hemorrhage is a frequent cause of iron-deficiency anemia, which may be poorly regenerative and sometimes becomes nonregenerative in severe cases.

A Wright’s stained blood film should be examined for findings consistent with hemolysis or RBC fragmentation such as erythroparasites, RBC agglutination, spherocytes, Heinz bodies, eccentrocytes, schistocytes, and keratocytes. Suspect agglutination should be confirmed with a saline dispersion test; rouleaux will disperse, while true antibody-mediated agglutination will persist. Immune-mediated hemolytic anemia may present as a non-regenerative anemia if the immune response is directed against RBC precursors in the bone marrow. Icterus may be seen with either intra- or extravascular hemolysis; presence of hemoglobinemia and hemoglobinuria suggests intravascular hemolysis. Heinz body hemolytic anemia may becaused by exposure to oxidants and has been associated with several primary disease processes in cats (lymphoma, diabetes mellitus, and hyperthy-roidism). Abnormalities commonly associated with either hemolysis or hemorrhage are presented in Table 54-3.

Nonregenerative anemia indicates decreased production of RBC in the bone marrow, assuming acute hemorrhage or hemolysis has been ruled out. Decreased RBC production may occur because of diseases extrinsic or intrinsic to the bone marrow. The most common causes extrinsic to the bone marrow are anemia of chronic disease (anemia secondary to inflammation) and chronic renal failure, which results in decreased erythropoietin production. The anemia of chronic disease is typically mild, while that of chronic renal failure may become severe. Both are typically normocytic (normal MCV) and normochromic (normal MCHC) anemias. Evaluation of the leukogram for evidence of inflammation and biochemical testing with urinalysis for evidence of renal disease are helpful. Microcytic, hypochromic (sometimes), nonregenerative, or poorly regenerative anemias are frequently due to iron deficiency, which in adult animals is almost always caused by chronic blood loss. Additional tests include a serum iron profile, fecal occult blood, and evaluation of the gastrointestinal tract. Mild nonregenerative anemia that is microcytic (decreased MCV) is also seen in dogs with portosystemic shunts. Macrocytic nonregenerative anemias in cats are often associated with FeLV infection. Presence of pancytopenia (nonregenerative anemia, thrombocytopenia, and neutropenia) should raise suspicion for an intrinsic bone marrow disorder. Bone marrow evaluation, testing for ehrlichiosis in dogs, and FeLV/FIV in cats should be considered.

TABLE 54-3. Regenerative anemia: differentiating hemolysis from hemorrhage

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