General Comments

• Usually secondary.
• Signs associated with primary disease often precede signs of anemia.

Historical Findings

• Lack of energy, exercise intolerance, inappetence, and cold intolerance.
• Other findings reflect primary condition: polyuria and polydipsia (e.g., CRF), paint exposure from remodeling old houses (e.g., lead poisoning), treating female dogs for mismating or urinary incontinence or feminization in male dogs (e.g., hyperestrogenism), failure to thrive observed at 8–12 weeks of age (hereditary cobalamin malabsorption).

Physical Examination Findings

• Pallor, heart murmur (severe anemia), and possibly tachycardia or polypnea.
• Signs reflecting primary condition: oral ulcerations (e.g., CRF), cachexia (e.g., cancer), organomegaly (e.g., lymphoma), gastrointestinal or CNS signs (e.g., lead poisoning), symmetrical alopecia (e.g., hypothyroidism and hyperestrogenism).

Nonregenerative Anemia without Other Cytopenias

• Anemia of inflammatory disease (AID)-most common cause of mild nonregenerative anemia; can be seen within 3–10 days of infection, inflammation, tissue injury, immune-mediated processes, and neoplasia; increased liver production of hepcidin and release of cytokines from T-lymphocytes and macrophages lead to iron sequestration in macrophages, decreased iron absorption; low serum iron and transferrin, increased ferritin, decreased EPO production and function, and shortened RBC lifespan.
• Chronic renal failure-kidneys fail to produce adequate EPO; uremic toxins shorten RBC lifespan and impair response to EPO.
• Chronic liver disease-shortened RBC survival caused by changes in RBC membrane lipids; functional iron deficiency due to decreased transferrin synthesis and impaired mobilization of hepatic iron.
• Endocrine disease-thyroid hormones and cortisol stimulate erythropoiesis and facilitate the effect of erythropoietin.
• Immune-mediated destruction of precursors-pure red cell aplasia.
• Infectious destruction of precursors (although usually > one cell line is involved), e.g., FeLV and ehrlichiosis, Cytauxzoon felis.

Nutritional or Mineral Deficiency/Toxicity

• Iron deficiency-usually due to chronic external blood loss; initially regenerative, but as severity increases, anemia becomes nonregenerative.
• Cobalamin (vitamin B₁₂) and/or folate deficiency-rare in dogs and cats; can be caused by dietary insufficiency, malabsorption, or chronic drug administration (e.g., sulfas, methotrexate, anticonvulsants) that inhibits folate; congenital defect in cobalamin absorption in giant schnauzers, border collies, Australian shepherd dogs, and beagles; can occasionally cause normocytic anemia and hypersegmented neutrophils; megaloblastic changes possible in the marrow.
• Disruption of precursor metabolism-chronic lead toxicity and possibly high concentrations of aluminum, arsenic, and cadmium inhibit heme synthesis; cadmium and lead cause renal toxicity and impaired EPO production.

Nonregenerative Anemia with Other Cytopenias

• Toxicities-drugs or chemicals (e.g., cancer chemotherapeutics, chloramphenicol, phenylbutazone, trimethoprim-sulfadiazine, zonisamide, phenobarbital, griseofulvin, methimazole, fenbendazole, albendazole, and benzene), hormones (e.g., estrogen toxicity secondary to abortifacient therapy and Sertoli cell tumor).
• Infections-FeLV, FIV, ehrlichiosis, babesiosis, and parvoviral infection (recovery usually precedes development of anemia).
• Infiltrative processes-myelodysplasia, myeloproliferative and lymphoproliferative diseases, metastatic neoplasia, myelofibrosis, and osteosclerosis.

Disorders That May Alter Laboratory Results

• Lipemia can falsely elevate hemoglobin and MCHC values.
• Lead toxicity-increased NRBC may falsely elevate the WBC count.

Valid If Run in Human Laboratory?

• Dogs-yes.
• Cats-yes, if hematology instrument uses species-specific parameters; instruments designed strictly for human specimens may under-count small feline RBCs.

CBC and Blood Smear

• PCV, RBC count, and hemoglobin low.
• Anemia usually normocytic, normochromic, with normal MCV and MCHC.
• Macrocytosis (high MCV)-without polychromasia suggests nuclear maturation defect (cells skip a division); seen in cats with FeLV; rarely caused by vitamin B₁₂ or folate deficiency.
• Microcytosis (low MCV)-suggests cytoplasmic maturation defect (cells undergo extra division); iron deficiency most common cause; in late stages, concurrent hypochromasia (low MCHC) common in dogs but not in cats; seen in approximately one-third of patients with hepatic insufficiency or vascular shunting.
• Specific RBC morphologies-schistocytes common with iron deficiency ± visibly hypochromic RBCs (dogs); acanthocytes with liver disease; target cells with iron deficiency, liver disease, and hypothyroidism.
• Inflammatory leukogram supports AID.
• Thrombocytosis common in iron deficiency.
• High number of NRBCs without polychromasia or disproportionate to the degree of anemia and polychromasia seen with lead toxicity, EMH, heat stroke, and injury to bone marrow stroma by endotoxemia or hypoxia.
• RBC or WBC precursors in peripheral blood without orderly progression to more mature forms suggest myelodysplasia or myeloproliferative disease.
• Concurrent cytopenia in other cell lines without evidence of marrow responsiveness (e.g., band neutrophils and macroplatelets) suggests generalized bone marrow injury.

Serum Biochemistry and Urinalysis

• CRF: high BUN and creatinine with inadequate urine concentration (dogs, <1.030; cats, <1.035).
• Liver disease: high ALT, total bilirubin, or elevated bile acids suggests liver disease.
• Hypothyroidism: high serum cholesterol (>500 mg/dL).
• Hypoadrenocorticism: Na/K <23, lymphocytosis, and eosinophilia.

Cytologic Examination of Bone Marrow and Core Biopsy

• Cytologic examination of aspirate indicated in all patients unless primary cause is apparent (e.g., AID and CRF).
• Bone marrow core biopsy-useful in evaluation of bone marrow architecture and overall cellularity; important for diagnosis of aplastic marrow or myelofibrosis.
• Erythroid hypoplasia or aplasia confirms the problem, although history and other tests may be needed to determine the underlying etiology.
• Myeloid hyperplasia and high iron stores support AID.
• Classically, iron deficiency has expanded erythron and high numbers of metarubricytes; absence of iron stores supportive in dogs, but not cats.
• Increased erythrophagocytosis suggests injury to cells (e.g., immune-mediated and toxic causes).
• Incomplete maturation sequence suggests injury to specific maturation stage (e.g., immune-mediated and toxic causes) or possibly incomplete recovery from a previous injury (recheck in 3–5 days).
• Disorderly maturation and atypical cellular morphology suggest myelodysplastic syndrome.
• Hypercellular marrow with increased blast cells (>20% of nucleated cells) indicates hematopoietic neoplasia; immunophenotyping can identify affected cell line(s); circulating neoplastic cells may or may not be seen.
• Non-marrow cells indicate metastatic neoplasia.

Abdominal Ultrasound

Evaluation of microcytic anemia; look for intestinal neoplasia or other source of external blood loss.