Overview

• Heinz bodies cause hemolytic anemia and indicate oxidative damage to RBCs.
• Heinz bodies form when oxidants overwhelm protective reductive pathways in RBCs; irreversible denaturation of the globin chains in hemoglobin causes precipitation and attachment of altered hemoglobin to the cell membrane.
• RBCs with Heinz bodies are targeted for removal by macrophages in the spleen, and occasionally undergo intravascular lysis.
• The pitting function of the spleen may remove Heinz bodies, resulting in spherocytes.
• Heinz bodies are usually caused by exposure to chemical or dietary oxidants.
• Cats are particularly susceptible to Heinz body formation because their hemoglobin contains more sulfhydryl groups than that of dogs.
• Healthy cats may have Heinz bodies with no anemia, possibly because cats have a nonsinusoidal spleen with limited pitting function.
• Heinz bodies are reported in hyperthyroidism (cats), lymphoma (cats, dogs), and diabetes mellitus (cats, dogs), possibly due to increased endogenous oxidants (e.g., -hydroxybutyrate in ketoacidosis). Anemia may or may not be present.
• Heinz bodies may be accompanied by methemoglobinemia (hemoglobin containing Fe³⁺) and/or eccentrocytes (oxidative damage to RBC membranes causing adhesion of opposing membranes and displacement of hemoglobin to one side of the cell).

Signalment

• Dogs and cats
• No sex, breed, or age disposition

Signs

Causes & Risk Factors

• Dietary: onions (raw, cooked, dehydrated, and powdered), garlic (dogs), propylene glycol (cats), Chinese chives (dog).
• Drugs: acetaminophen, phenacetin (cats), phenazopyridine (cats), methylene blue, vitamin K1 or K3 (dogs), DL-methionine (cats), benzocaine (topical), phenylhydrazine (dog), propofol (cats).
• Miscellaneous: zinc (nuts, bolts, pennies, dermatologic creams), naphthalene (moth ball ingestion in dogs), skunk musk exposure (dogs).

Differential Diagnosis

• Other causes of regenerative, hemolytic anemia (e.g., immune mediated, hemoparasites).
• Heinz bodies may be found in healthy or ill cats without anemia. Diagnosis of a Heinz body anemia requires documentation of a regenerative anemia, supporting evidence of a hemolytic process (e.g. hyperbilirubinemia), identification of Heinz bodies on a blood smear, and elimination of other causes of hemolysis or blood loss.

CBC/Biochemistry/Urinalysis

• Regenerative anemia (decreased HCT, polychromasia, nucleated RBCs) is expected if there has been sufficient time for a bone marrow response; the severity of anemia depends on dose of oxidant and duration of exposure.
• Hemoglobin concentration and MCHC may be falsely increased due to Heinz body interference with hemoglobin measurement.
• Heinz bodies are visible on a routinely stained blood smear as small, pale red, round inclusions that may protrude from RBC surface. They may be difficult to identify if there is marked poikilocytosis.
• Single, small (<0.5 µm) Heinz bodies may be found in RBCs of cats without anemia.
• Large and/or multiple Heinz bodies in an anemic cat suggest a Heinz body hemolytic anemia.
• Dogs may have concurrent eccentrocytosis on a blood smear.
• Hyperbilirubinemia and bilirubinuria are possible.
• Hemoglobinemia and hemoglobinuria are uncommon but occur with severe intravascular hemolysis.
• Neutrophilia and monocytosis may occur.

Other Laboratory Tests

• New methylene blue stains Heinz bodies blue, making them easy to identify and quantify on a blood smear, even with marked poikilocytosis.
• Measure methemoglobin if blood is dark or chocolate colored.
• Serum zinc concentration if indicated.

Imaging

Abdominal radiographs may reveal gastrointestinal metal objects in zinc toxicity.

Drug(s) Of Choice

Acetaminophen toxicity in cats-N- acetylcysteine (140 mg/kg PO or IV, followed by seven additional treatments of 70 mg/kg q8h).

Contraindications/Possible Interactions

Administration of methylene blue to treat methemoglobinemia may exacerbate Heinz body formation.

Alternative Drug(s)

The use of dietary antioxidants (e.g., bioflavonoids) is controversial but may help prevent further formation of Heinz bodies.

Patient Monitoring

Serial CBCs and review of blood smears are recommended to assess RBC regeneration and disappearance of Heinz bodies.

Prevention/Avoidance

Counsel clients about preventing exposure to oxidants.

Possible Complications

N/A

Expected Course and Prognosis

Prognosis is good with removal of oxidant and supportive care once the hemolytic crisis is over.

See Also

• Acetaminophen (APAP) Toxicosis
• Anemia, Regenerative
• Methemoglobinemia
• Zinc Toxicosis

Abbreviations

• HCT = hematocrit
• MCHC = mean corpuscular hemoglobin concentration
• RBC = red blood cell