A patient presents with acute self-limited intravascular hemolysis with hemoglobinemia and hemoglobinuria—what do you suspect?

• A. G6PD deficiency
• B. Paroxysmal nocturnal hemoglobinuria
• C. Cold agglutinin disease
• D. Sickle cell disease

Answer: (A)

Acute, self-limited intravascular hemolysis with hemoglobinemia and hemoglobinuria is classic for a deficiency in the RBC’s ability to handle oxidative stress. In G6PD deficiency, the hexose monophosphate pathway can’t generate enough NADPH. That leaves glutathione in the oxidized form, so oxidative insults—such as certain drugs (like sulfonamides or dapsone), fava beans, or other oxidants—damage hemoglobin and the RBC membrane. The result is intravascular hemolysis, with free hemoglobin appearing in the plasma (hemoglobinemia) and in the urine (hemoglobinuria). Once the oxidative trigger is removed, the hemolysis subsides and recovery occurs.

This pattern helps distinguish it from paroxysmal nocturnal hemoglobinuria, which is due to absence of GPI-anchored proteins and tends to cause ongoing hemolysis with risk of pancytopenia and thrombosis rather than being an acute, toxin-triggered, self-limited episode. Cold agglutinin disease involves IgM-mediated, complement-driven hemolysis that is linked to cold exposure and often has a different clinical picture and lab findings. Sickle cell disease typically shows chronic hemolysis with episodic crises driven by sickling of HbS rather than a transient oxidative-stress–driven event.