A 25-year-old African American man is admitted to the hospital due to sudden-onset back pain, dark urine, and a day of fatigue. Four days ago, the patient began taking trimethoprim-sulfamethoxazole for right arm cellulitis. Yesterday he was unable to go to work due to fatigue and weakness. Medical history is otherwise unremarkable. Physical examination shows conjunctival pallor and improving cellulitis. Laboratory results are as follows: Peripheral smear shows bite cells. Glucose-6-phosphate dehydrogenase activity assay is sent on admission and returns within normal limits. Which of the following is the most likely cause of this patient's hemolysis?

Question

A 25-year-old African American man is admitted to the hospital due to sudden-onset back pain, dark urine, and a day of fatigue.  Four days ago, the patient began taking trimethoprim-sulfamethoxazole for right arm cellulitis.  Yesterday he was unable to go to work due to fatigue and weakness.  Medical history is otherwise unremarkable.  Physical examination shows conjunctival pallor and improving cellulitis.  Laboratory results are as follows:  Peripheral smear shows bite cells.  Glucose-6-phosphate dehydrogenase activity assay is sent on admission and returns within normal limits.  Which of the following is the most likely cause of this patient's hemolysis?

Quizplus · Accepted Answer

11ec25c8_d415_3813_bc81_e5b94c5861ab_MD0003_00 This patient developed hemolytic anemia after receiving trimethoprim-sulfamethoxazole, raising strong suspicion for glucose-6-phosphate dehydrogenase (G6PD) deficiency. This X-linked, inherited disorder is seen in ~10% of black men but also occurs in those of Mediterranean, Asian, and Middle Eastern descent. Patients are generally asymptomatic but develop hemolysis when exposed to oxidative stressors such as infection, medications (eg, trimethoprim-sulfamethoxazole, nitrofurantoin, primaquine), or certain foods (eg, fava beans). Hemolysis generally manifests with pallor and fatigue (due to anemia), jaundice (due to elevated bilirubin) and dark urine (due to hemoglobinuria), and back/abdominal pain. Laboratory results will show low hemoglobin, elevated indirect bilirubin, elevated lactate dehydrogenase, and decreased haptoglobin. Peripheral blood smear typically reveals Heinz bodies (oxidized/precipitated hemoglobin) and bite cells (bite-shaped membrane defects due to removal of Heinz bodies by splenic macrophages). Coombs testing will be negative, unlike antibody-mediated forms of hemolysis. bite cells G6PD activity testing can be normal (low sensitivity) in acute hemolytic episodes because older erythrocytes (lowest G6PD activity) have been hemolyzed and young erythrocytes/reticulocytes (higher G6PD activity) are disproportionally elevated. Therefore, in such settings, this test cannot be used to rule out G6PD deficiency; repeat testing should be done at 3 months to confirm the diagnosis in those whose initial test was negative. No intervention is generally required other than removing or treating the inciting oxidative stress. (Choice A) Galactokinase deficiency does not cause hemolytic anemia. The classic manifestation of this condition is bilateral cataract development. (Choice C) Hereditary spherocytosis is a genetic disorder associated with chronic hemolytic anemia due to erythrocyte membrane defects. However, mean corpuscular hemoglobin concentration will be >36 g/dL, and blood smear will show spherocytes. spherocytes (Choice D) Pyruvate kinase deficiency is an autosomal recessive disorder that causes chronic hemolysis, hepatosplenomegaly, skin ulcers, and pigmented gallstones. Unlike with G6PD deficiency, hemolysis is constant, so there is no relationship to inciting events (eg, sulfa drug exposure). (Choice E) Sickle cell crisis is associated with worsened hemolytic anemia and acute pain. Peripheral blood smear will show sickle cells or Howell-Jolly bodies. sickle cells Educational objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency causes episodic hemolytic anemia after oxidative insults (eg, sulfa drugs, primaquine, infection, fava beans). Laboratory studies show hemolytic anemia (eg, elevated lactate dehydrogenase/bilirubin, low haptoglobin), and peripheral blood smear typically demonstrates bite cells and Heinz bodies. Diagnosis is made by G6PD activity level, but sensitivity is low in acute hemolytic crises; therefore, this test cannot be relied on to rule out the condition in the acute setting. References: Diagnosis and management of G6PD deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/16225031) Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. (http://www.ncbi.nlm.nih.gov/pubmed/18156501)

A 25-Year-Old African American Man Is Admitted to the Hospital