A 12-year-old boy with cystic fibrosis is admitted to the hospital for fever, chills, shortness of breath, and worsened productive cough. The patient has been hospitalized multiple times for lung infections. Chest imaging reveals patchy lung infiltrates. Blood and sputum cultures are ordered, and piperacillin-tazobactam is started. Several hours later, the patient develops increased dyspnea, weakness, and new-onset back pain. Repeat examination shows tachycardia, mucosal pallor, and dark urine. No midline back tenderness or lower extremity neurologic deficits are present. Laboratory results are as follows: Hemoglobin on admission was 11.8 g/dL. Which of the following is the most likely cause of this patient's clinical deterioration after hospitalization?

Question

A 12-year-old boy with cystic fibrosis is admitted to the hospital for fever, chills, shortness of breath, and worsened productive cough.  The patient has been hospitalized multiple times for lung infections.  Chest imaging reveals patchy lung infiltrates.  Blood and sputum cultures are ordered, and piperacillin-tazobactam is started.  Several hours later, the patient develops increased dyspnea, weakness, and new-onset back pain.  Repeat examination shows tachycardia, mucosal pallor, and dark urine.  No midline back tenderness or lower extremity neurologic deficits are present.  Laboratory results are as follows:  Hemoglobin on admission was 11.8 g/dL.  Which of the following is the most likely cause of this patient's clinical deterioration after hospitalization?

Quizplus · Accepted Answer

11ec25c8_d69b_bc2b_bc81_79bc55b6383c_MD0003_00 This hospitalized patient's acute anemia, dark-colored urine, and normal coagulation studies raise strong suspicion for drug-induced hemolytic anemia. The most common triggers are nonsteroidal anti-inflammatory drugs (eg, diclofenac), cephalosporins (eg, ceftriaxone), and penicillins (eg, piperacillin-tazobactam). Although drugs can cause hemolysis through a variety of mechanisms (eg, oxidative injury, complement-mediated lysis), penicillins and cephalosporins trigger hemolysis when the drug binds directly to the surface of erythrocytes and creates a hapten for IgG attachment. IgG-coated erythrocytes are then identified by the Fc receptor on splenic macrophages, leading to partial or whole erythrocyte phagocytosis (extravascular hemolysis). Intravascular hemolysis may also occur due to activation of the complement cascade. Manifestations typically arise within hours of drug exposure and include signs of anemia (eg, dyspnea, pallor, weakness) and hemolysis (eg, jaundice, dark-colored urine [hemoglobinuria]). Back pain can sometimes occur in severe cases, possibly due to increased erythrocytosis in the vertebral bone marrow. Laboratory evaluation will reveal increased indirect bilirubin, reticulocytosis, and, with intravascular hemolysis, elevated lactate dehydrogenase and lowered haptoglobin. Peripheral blood smear typically shows immature red blood cells (eg, normoblasts) and spherocytes due to the partial removal of erythrocyte membrane by splenic macrophages. The diagnosis is confirmed with direct antiglobulin (Coombs) testing, which detects anti-IgG (or anti-C3) bound to the erythrocyte surface. Discontinuing the offending drug is generally curative. spherocytes (Choice A) Acute retroperitoneal hemorrhage can present with back pain, hematuria, and acute anemia but typically occurs after trauma (most common) or spontaneously due to a coagulation disorder. This patient has no history of trauma, and his normal PT and PTT make a coagulation disorder unlikely. (Choice B) Although disseminated intravascular coagulation (DIC), a consumptive coagulopathy associated with the formation of intravascular microthrombi, is a common cause of hemolysis during severe infection (eg, pneumonia), patients with DIC have prolonged coagulation studies due to the consumption of clotting factors. Schistocytes also are typically seen on peripheral blood smear due to erythrocyte shearing in the microvasculature. Schistocytes (Choice D) Infection-induced glomerulonephritis can present with back pain and hematuria. However, anemia in response to glomerulonephritis typically occurs over days, not hours. (Choice E) Although anaphylaxis can cause tachycardia and shortness of breath, it typically occurs within seconds or minutes after medication administration and is associated with rash and edema. Anemia is atypical. Educational objective: Penicillins and cephalosporins can cause drug-induced immune hemolysis by binding to the surface of red blood cells and triggering an IgG antibody response. Patients typically develop acute anemia and signs of hemolysis (eg, jaundice, dark urine) within hours of antibiotic administration. References: Immune hemolytic anemia caused by drugs. (http://www.ncbi.nlm.nih.gov/pubmed/22502777)

A 12-Year-Old Boy with Cystic Fibrosis Is Admitted to the Hospital