A: Anemia, Nuclear Maturation Defects (Anemia, Megaloblastic)

Anemia, Nuclear Maturation Defects (Anemia, Megaloblastic)

BASICS

OVERVIEW

Nonregenerative anemia characterized by arrested development of the nuclei of RBC precursors (as a result of interference with DNA synthesis) while the cytoplasm develops normally (nuclear-cytoplasmic asynchrony).
Affected RBC precursors fail to divide normally and thus are larger than corresponding normal precursors with the same degree of cytoplasmic maturity (hemoglobinization); because their nuclei are deficient in chromatin (DNA), they have a distinctive open and stippled appearance; these giant precursors with atypical, immature nuclei are known as megaloblasts.
Although these asynchronous changes are most prominent in RBC precursors, WBC and platelet precursors are similarly affected.

SIGNALMENT

SIGNS

In dogs, generally mild, usually not clinically important.
In cats with FeLV-associated nuclear maturation anemia, FeLV-related signs can be anticipated. Anemia may be mild to severe.

CAUSES & RISK FACTORS

Infectious—FeLV; retroviral infection the most common cause of megaloblastic anemia in cats.
Nutritional—folic acid and vitamin B12 deficiencies.
Toxic—phenytoin (Dilantin) toxicity and methotrexate toxicity (folate antagonist).
Congenital—toy poodles.

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

In dogs, all other mild to moderate nonregenerative anemias, including anemia of inflammatory disease, renal disease, and lead poisoning.
Differentiation based on the distinctive CBC and bone marrow findings listed.
In cats, FeLV infection is the primary differential.

CBC/BIOCHEMISTRY/URINALYSIS

In dogs, mild to moderate anemia (PCV: 30–40%).
In cats, anemia can be mild to severe.
Anemia classically macrocytic (high mean corpuscular volume) and normochromic (normal mean corpuscular hemoglobin concentration).
Large, fully hemoglobinized RBC; occasional to numerous megaloblasts, particularly at the feather edge; minimal to no polychromasia.
In cats with FeLV, anemia may occur in association with a myelodysplastic syndrome or in conjunction with leukemia of a different cell line.

OTHER LABORATORY TESTS

FeLV

IMAGING

N/A

OTHER DIAGNOSTIC PROCEDURES

Bone Marrow Biopsy

In dogs, usually hyperplastic, often in all cell lines.
In cats, marrow findings are highly variable and may be hyper- to hypocellular.
Maturation arrest with nuclear and cytoplasmic asynchrony in all cell lines.
Many megaloblastic RBC precursors may be observed.
Macrophagic hyperplasia with active phagocytosis of nucleated RBCs and megaloblasts (common).

TREATMENT

Treat by targeting the underlying cause if possible.
Except for that occurring with FeLV in cats, megaloblastic anemia is a relatively mild condition.
Treat most patients on an outpatient basis.

MEDICATIONS

DRUG(S)

In animals with drug toxicity, discontinue the offending drug.
In all animals, consider supplementation with folic acid (4–10 mg/kg/day) or vitamin B12 (dogs, 100–200 mg/day PO; cats, 50–100 mg/day PO).
Giant schnauzers with inherited cobalamin malabsorption require parenteral treatment with vitamin B12 (0.5–1 mg IM weekly to every few months).

CONTRAINDICATIONS/POSSIBLE INTERACTIONS

Drugs known to cause megaloblastic anemia (e.g., methotrexate and phenytoin) should be avoided in patients whose condition results from other causes.

FOLLOW-UP

Monitor response to treatment by CBC (weekly) and occasional bone marrow collection and evaluation.
Closely monitor FeLV-positive cats for evidence of onset of other signs of hematopoietic dyscrasia in the peripheral blood and bone marrow.
Prognosis—depends on underlying cause; in FeLV-positive cats, prognosis guarded; in animals with drug-associated anemia, prognosis good when use of offending drug is interrupted.

MISCELLANEOUS