A 32-year-old African American male is diagnosed with acute prostatitis. He has no significant past medical history. He begins treatment with trimethoprim-sulfamethoxazole, but subsequently develops dark urine and anemia with a high reticulocyte count. Which of the following is the best explanation for the observed findings?

Question

A 32-year-old African American male is diagnosed with acute prostatitis.  He has no significant past medical history.  He begins treatment with trimethoprim-sulfamethoxazole, but subsequently develops dark urine and anemia with a high reticulocyte count.  Which of the following is the best explanation for the observed findings?

Quizplus · Accepted Answer

This patient is demonstrating signs of hemolysis induced by trimethoprim-sulfamethoxazole (Bactrim, TMP/SMX). This scenario is not an uncommon way for glucose-6-phosphate dehydrogenase (G6PD) deficiency to present. G6PD deficiency is an X-linked disorder that affects mostly males, and is more common in patients of African, Asian and Mediterranean descent. G6PD is an enzyme of the pentose phosphate pathway that in erythrocytes is essential for maintaining adequate concentrations of NADPH. Insufficient NADPH results in an inability to maintain glutathione in the reduced state. This increases the vulnerability of erythrocytes to oxidative stress and manifests with hemolysis induced by infection, drugs (e.g. bactrim, dapsone, antimalarials, nitrofurantoin), or other oxidants (e.g. fava beans). Hemolytic episodes manifest with symptoms of anemia such as malaise and pallor, indirect bilirubinemia (jaundice), hemoglobinemia and hemoglobinuria (dark-red urine). The level of serum haptoglobin decreases and a reticulocytosis develops to compensate for the increased destruction of RBCs. Patients are generally asymptomatic between episodes. (Choice A) Autoimmune hemolytic anemias result from extrinsic antibody-mediated hemolysis and are associated with a positive Coombs test. These anemias often accompany SLE and other autoimmune diseases, Hodgkin and non-Hodgkin lymphomas, Mycoplasma infections (cold agglutinins), and infectious mononucleosis. (Choice B) Hereditary spherocytosis is an autosomal dominant defect in RBC structural proteins (spectrin, ankyrin, or protein 4.1) characterized by increased erythrocyte osmotic fragility and MCHC (mean corpuscular hemoglobin concentration) increased above 36 g/dL. (Choice D) Abnormalities of hemoglobin structure include hemoglobin S (sickle cell disease), C, and E disorders, as well as others. Heterozygotes usually show minimal to no clinical signs, while homozygotes present with hemolytic anemia in addition to other disease-specific complications. (Choice E) Microangiopathic hemolytic anemia (MAHA) occurs when there is destruction of RBCs within small vessels due to widespread thrombosis. MAHA is associated with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). Educational Objective: Glucose-6-phosphate dehydrogenase deficiency is an X-linked disorder of the hexose monophosphate (pentose phosphate) pathway. In affected individuals, the amount of NADPH produced in RBCs is low, which impairs glutathione-mediated inactivation of free radicals. Hemolytic episodes are induced by infections, medications, and other oxidants.

A 32-Year-Old African American Male Is Diagnosed with Acute Prostatitis