Which laboratory finding best distinguishes G6PD deficiency from autoimmune hemolytic anemia (AIHA)?

Distinguishing G6PD Deficiency from Autoimmune Hemolytic Anemia

Pathophysiology and Laboratory Differentiation

Heinz bodies on supravital staining are the pathognomonic finding in G6PD deficiency. These are denatured hemoglobin precipitates (Heinz-Koehler bodies) that form when oxidative stress overwhelms the RBC's antioxidant defense. They are absent in AIHA, where the primary mechanism is antibody-mediated RBC destruction.

The DAT/Coombs test is the gold standard discriminator between these two conditions:

However, since the question asks for the best discriminating feature among the options, Heinz bodies are the most specific morphologic finding unique to G6PD.

"HEINZ = Hemoglobin Enzyme deficiency (G6PD)" — Heinz bodies are pathognomonic for G6PD deficiency.

Bite cells (RBCs with a "bite" taken out, representing Heinz body removal by the spleen) are also characteristic of G6PD deficiency and are never seen in AIHA. Spherocytes, conversely, are the hallmark of AIHA and are absent in G6PD deficiency unless there is concurrent hereditary spherocytosis.

When you see Heinz bodies on supravital staining, immediately think G6PD deficiency. When you see positive DAT + spherocytes, think AIHA.

Robbins 10e Ch 13