A 22-year-old man comes to the emergency depament because of dyspnea, palpitations, and a headache. These symptoms came on soon after he took trimethoprim-sulfamethoxazole for a urinary tract infection. Laboratory studies show a normochromic, normocytic anemia. A peripheral blood smear reveals Heinz bodies. Which of the following is the most likely cause of this patient’s anemia?

**Core Concept**
The patient's symptoms and laboratory findings suggest a hemolytic anemia, which is characterized by the premature destruction of red blood cells. Trimethoprim-sulfamethoxazole is a common cause of drug-induced hemolytic anemia, particularly in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

**Why the Correct Answer is Right**
The patient's symptoms of dyspnea, palpitations, and headache, along with the laboratory findings of normochromic, normocytic anemia and Heinz bodies on the peripheral blood smear, are consistent with a hemolytic anemia. Trimethoprim-sulfamethoxazole can induce hemolysis in individuals with G6PD deficiency by generating reactive oxygen species that deplete NADPH and impair the red blood cell membrane. The presence of Heinz bodies, which are denatured hemoglobin, further supports this diagnosis.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because it does not address the specific mechanism by which trimethoprim-sulfamethoxazole causes hemolysis. While oxidative stress is involved, it is not the primary mechanism.

**Option B:** This option is incorrect because it does not account for the specific role of G6PD deficiency in the patient's hemolysis. While other enzymes may be involved in red blood cell metabolism, G6PD is the primary enzyme affected in this scenario.

**Option C:** This option is incorrect because it does not address the specific relationship between trimethoprim-sulfamethoxazole and hemolysis. While certain medications can cause hemolysis in individuals with G6PD deficiency, this option does not provide a clear mechanism.

**Option D:** This option is incorrect because it does not account for the specific laboratory findings, such as Heinz bodies, that are characteristic of this patient's hemolytic anemia.

**Clinical Pearl / High-Yield Fact**
G6PD deficiency is a common genetic disorder that affects approximately 400 million people worldwide. Individuals with G6PD deficiency are at increased risk of hemolysis when exposed to certain medications, including trimethoprim-sulfamethoxazole, and should avoid these medications whenever possible.

**Correct Answer:** C. Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

✓ Correct Answer: C. Glucose-6-phosphate dehydrogenase deficiency