A 24-year-old African-American man comes to the office after a rapid HIV test was positive at a health fair. Additional laboratory evaluation reveals a HIV viral load of 240,000 copies/mL and a CD4 count of 180 cells/mm³. The patient is given a prescription for antiretroviral therapy. He is also given dapsone for Pneumocystis jiroveci pneumonia prophylaxis due to a history of rash with trimethoprim-sulfamethoxazole. Pneumococcal and influenza vaccines are administered. A few days later, the patient returns to the office due to fatigue, jaundice, and dark urine. Laboratory results now show the following: Coagulation studies are within normal limits. Peripheral smear reveals red blood cell fragments, microspherocytes, and bite cells. Which of the following is the most likely underlying cause of this patient's symptoms?

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11ec160b_3977_1722_9249_cfac17cd8ded_MD0001_00 This patient developed symptomatic anemia (eg, fatigue) and signs of hemolysis (eg, jaundice, dark urine) after taking dapsone for a few days, indicating likely glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD catalyzes the first step of NADPH production. Because NADPH is required to generate the reduced form glutathione (a potent antioxidant), patients with G6PD deficiency lack sufficient reductive capacity to handle significant oxidative stressors and typically develop erythrocyte damage/lysis with acute infection, oxidative foods (eg, fava beans), and oxidative medications (eg, dapsone, primaquine). Oxidative injury to erythrocytes causes hemoglobin precipitation on the erythrocyte membrane (Heinz body) and impairs erythrocyte deformation while passing through the narrow sinusoids of the spleen. The damaged erythrocytes are identified and removed by splenic macrophages, leading to extravascular hemolysis. Patients typically develop manifestations 2-4 days after the oxidative injury, including acute anemia and signs of elevated bilirubin (eg, dark urine, jaundice). Laboratory evaluation generally shows significant reticulocytosis because the bone marrow increases erythrocytosis to compensate for the anemia. Peripheral smear generally shows hemoglobin precipitation (Heinz bodies) on the periphery of red blood cells and bite cells due to phagocytic removal of precipitated hemoglobin by splenic macrophages. Because mild intravascular hemolysis also occurs (due to intravascular erythrocyte lysis from oxidative damage), schistocytes (fragmented red blood cells) and microspherocytes (round, dense schistocytes) are also frequently seen on peripheral smear. (Choice A) Sickle cell anemia is a genetic mutation associated with erythrocyte sickling in the setting of deoxygenation and dehydration. Blood smear shows sickled red blood cells (not schistocytes), bite cells, and microspherocytes. (Choice B) Disseminated intravascular coagulation is a consumptive coagulopathy characterized by intravascular clot formation, which shears red blood cells. Although schistocytes are seen on peripheral smear, Heinz bodies and bite cells are not. In addition, these patients have significant thrombocytopenia and prolonged coagulation times. (Choice D) Hereditary spherocytosis, a genetic disorder marked by erythrocyte cytoskeleton abnormalities, is marked by abundant spherocytes, but not bite cells or schistocytes. In addition, this patient developed symptoms after dapsone administration, making G6PD more likely. (Choice E) Pneumococcal and influenza vaccination does not typically trigger hemolysis. These vaccines can sometimes cause Guillain-Barré syndrome or rash. Educational objective: Glucose-6-phosphate dehydrogenase deficiency is characterized by episodes of hemolytic anemia following oxidative stress (eg, fava beans, dapsone, acute infection). Patients generally have jaundice, dark urine, normocytic anemia, reticulocytosis, and evidence of bite cells and Heinz bodies on peripheral smear.

A 24-Year-Old African-American Man Comes to the Office After a Rapid