A 5-year-old girl is brought to the emergency department due to 3 days of fever and cough. Physical examination shows increased respiratory effort and right-sided crackles. Neutrophilic leukocytosis and a right lower lobe consolidation are present. The patient is admitted to the hospital, and intravenous ceftriaxone and azithromycin are started. An hour later, the patient reports upper abdominal discomfort, and the urine is noted to be dark colored. On repeat examination, the patient appears listless and has tachycardia, tachypnea, and mild upper abdominal tenderness. Repeat laboratory results are as follows: Which of the following is most likely to reveal the cause of this patient's deterioration after hospitalization?

Question

A 5-year-old girl is brought to the emergency department due to 3 days of fever and cough.  Physical examination shows increased respiratory effort and right-sided crackles.  Neutrophilic leukocytosis and a right lower lobe consolidation are present.  The patient is admitted to the hospital, and intravenous ceftriaxone and azithromycin are started.  An hour later, the patient reports upper abdominal discomfort, and the urine is noted to be dark colored.  On repeat examination, the patient appears listless and has tachycardia, tachypnea, and mild upper abdominal tenderness.  Repeat laboratory results are as follows:  Which of the following is most likely to reveal the cause of this patient's deterioration after hospitalization?

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11ec25c8_d69c_7f7d_bc81_f5ac4971282f_MD0003_00 This patient developed dark-colored urine, elevated bilirubin, and anemia shortly after receiving antibiotics, raising strong suspicion for drug-induced hemolytic anemia. The most common triggers are nonsteroidal anti-inflammatory drugs (eg, diclofenac), penicillins (eg, piperacillin), and cephalosporins (eg, ceftriaxone). Although medications can trigger hemolysis through a variety of mechanisms (eg, oxidative injury, complement-mediated injury), penicillins and cephalosporins typically cause hemolysis when they bind to the erythrocyte surface, acting as a hapten that facilitates IgG attachment. Subsequently, the IgG-coated erythrocytes are destroyed by splenic macrophages, leading to extravascular hemolysis. Manifestations typically arise within hours or a few days of drug administration and include signs of anemia (eg, tachycardia, dyspnea) and hemolysis (eg, elevated bilirubin, dark-colored urine). Severe hemolysis can cause back or abdominal pain due to erythrocytosis in the vertebral bodies, liver, and spleen. Laboratory evaluation usually shows increased bilirubin, lactate dehydrogenase, and reticulocytes; haptoglobin, which binds free hemoglobin, will be very low. The diagnosis of immune-mediated hemolysis is made with the direct antiglobulin (Coombs) test, which detects IgG or C3 (a complement component) on the erythrocyte surface. Withdrawal of the offending drug typically leads to resolution of symptoms within hours or days. However, blood transfusion or corticosteroids are sometimes required in severe cases. (Choices B and D) Abdominal CT scan or liver ultrasonography can diagnose biliary obstruction and choledocholithiasis. Although these conditions are often associated with elevated bilirubin, patients typically have severe (not mild) abdominal pain, elevated alkaline phosphatase, and elevated liver function tests. This patient's anemia, normal alkaline phosphatase/liver function tests, and mild abdominal pain make biliary obstruction less likely. (Choice C) Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk for acute hemolysis after exposure to oxidizing foods (eg, fava beans) or medications (eg, sulfa drugs). However, ceftriaxone and azithromycin due not typically incite hemolysis in these patients. In addition, symptoms usually arise 2-4 days after drug exposure, not within hours. (Choice E) Serum fibrinogen is rapidly consumed in disseminated intravascular coagulation (DIC), a consumptive coagulopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and prolonged coagulation times. This patient's normal platelet count makes DIC unlikely. Educational objective: Drug-induced immune hemolysis can be triggered by penicillin and cephalosporin antibiotics, which bind to the surface of erythrocytes and act as a hapten for IgG attachment. IgG-coated erythrocytes are then destroyed by splenic macrophages (extravascular hemolysis), leading to anemia and signs of hemolysis (eg, jaundice, hemoglobinuria, elevated indirect bilirubin). The diagnosis is made with a Coombs test, which detects IgG on the erythrocyte surface. References: Ceftriaxone-induced immune hemolytic anemia. (http://www.ncbi.nlm.nih.gov/pubmed/25163809) Immune hemolytic anemia caused by drugs. (http://www.ncbi.nlm.nih.gov/pubmed/22502777)

A 5-Year-Old Girl Is Brought to the Emergency Department Due