A 23-year-old African American man returns to the physician because of jaundice, dark urine, and fatigue. He was seen in the clinic 4 days ago for sinusitis and was prescribed trimethoprim-sulfamethoxazole. He reports that his sinus symptoms have improved. He has no other medical problems and takes no other medications. He does not use tobacco, alcohol, or illicit drugs.
Vitals signs are normal. Physical examination shows scleral icterus. Abdominal examination is unremarkable with no evidence of hepatosplenomegaly.
Laboratory results are as follows:

Peripheral blood smear shows many bite cells. Direct and indirect Coombs' test is negative. Red blood cell glucose-6-phosphate dehydrogenase level is normal.
Which of the following is the most likely cause of his anemia?

Question

A 23-year-old African American man returns to the physician because of jaundice, dark urine, and fatigue.  He was seen in the clinic 4 days ago for sinusitis and was prescribed trimethoprim-sulfamethoxazole.  He reports that his sinus symptoms have improved.  He has no other medical problems and takes no other medications.  He does not use tobacco, alcohol, or illicit drugs.
Vitals signs are normal.  Physical examination shows scleral icterus.  Abdominal examination is unremarkable with no evidence of hepatosplenomegaly.
Laboratory results are as follows:

Peripheral blood smear shows many bite cells.  Direct and indirect Coombs' test is negative.  Red blood cell glucose-6-phosphate dehydrogenase level is normal.
Which of the following is the most likely cause of his anemia?

Quizplus · Accepted Answer

11ec193a_9828_05e1_853d_53d5222de8d7_MD0002_00 The onset of acute hemolysis after treatment with TMP-SMX, negative direct and indirect anti-globulin (Coombs') test, and the presence of "bite cells" on peripheral smear is consistent with a diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency, an X-linked disorder, is the most common enzymatic disorder of erythrocytes and is seen in the African American and Mediterranean populations. Oxidative stress is commonly induced by: Medications (e.g., dapsone, antimalarials, sulfonamide antibiotics) Favism (ingestion of fresh fava beans; common in G6PD Mediterranean) Infections Metabolic abnormalities (e.g., diabetic ketoacidosis) Medications (e.g., dapsone, antimalarials, sulfonamide antibiotics) Favism (ingestion of fresh fava beans; common in G6PD Mediterranean) Infections Metabolic abnormalities (e.g., diabetic ketoacidosis) Typically, patients present two to four days after an oxidatively stressful event with evidence of hemolysis (e.g., 3-4 g/dL drop in hemoglobin concentration) with a concomitant rise in reticulocytes. In this process, the older deficient RBCs are replaced by the younger cells, which have sufficient G6PD enzyme activity to sustain further oxidative damage without hemolysis. Additional laboratory findings include elevated lactate dehydrogenase and indirect bilirubin, and decreased haptoglobin. The peripheral smear also shows "bite" cells (black arrows in above figure). Since reticulocytes can have normal G6PD levels, measuring G6PD levels during an acute episode can produce normal results. If a false negative is suspected, it is recommended to recheck the G6PD level 2 to 3 months after the hemolytic episode. The main treatment for G6PD deficiency is avoidance of oxidative stressors; and rarely, if the anemia is severe enough, a blood transfusion. (Choice A) The most common type of autoimmune hemolytic anemia is warm antibody-mediated. In this disorder, spherocytes will be present on the peripheral smear and the direct Coombs' test will be positive. (Choice C) Paroxysmal nocturnal hemoglobinuria (PNH) is associated with pancytopenia, hemolytic anemia, and thrombosis. (Choice D) Pyruvate kinase (PK) deficiency is the second most common cause of enzyme-deficient hemolytic anemia following G6PD deficiency. Pyruvate kinase deficiency differs from G6PD deficiency in that erythrocytes from PK patients are not subject to hemolysis following oxidative stress. In addition, there are no characteristic morphologic red cell abnormalities on peripheral smear. (Choice E) Patients with microangiopathic hemolytic anemia have schistocytes on the peripheral blood smear and often have a low platelet count. Educational objective: Testing for G6PD deficiency during an acute hemolytic episode may produce a false negative result as the older and more deficient erythrocytes are destroyed and replaced by reticulocytes that commonly have normal G6PD levels. If a false negative is suspected, it is recommended to recheck the G6PD level 2 to 3 months after the hemolytic episode. __________ References: Diagnosis and Management of G6PD Deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/16225031)

A 23-Year-Old African American Man Returns to the Physician Because