A 62-year-old woman is being evaluated for worsening anemia. The patient was admitted to the hospital 2 days ago due to acute pyelonephritis. She has been treated with intravenous ceftriaxone, and her fever and urinary symptoms have gradually improved. The patient has no history of anemia and has had no symptoms of urinary or gastrointestinal bleeding. Laboratory results are as follows: Her antibiotics are changed to a different medication class, and the patient is discharged a few days later. At a follow-up office visit 2 weeks later, her laboratory abnormalities have resolved. Which of the following is the most likely cause of this patient's anemia?

Question

A 62-year-old woman is being evaluated for worsening anemia.  The patient was admitted to the hospital 2 days ago due to acute pyelonephritis.  She has been treated with intravenous ceftriaxone, and her fever and urinary symptoms have gradually improved.  The patient has no history of anemia and has had no symptoms of urinary or gastrointestinal bleeding.  Laboratory results are as follows:  Her antibiotics are changed to a different medication class, and the patient is discharged a few days later.  At a follow-up office visit 2 weeks later, her laboratory abnormalities have resolved.  Which of the following is the most likely cause of this patient's anemia?

Quizplus · Accepted Answer

11ec160b_3be2_98ae_9249_65e9d030c00c_MD0001_00 This patient developed anemia and hyperbilirubinemia during treatment with ceftriaxone, raising strong suspicion for drug-induced hemolytic anemia. The most common triggers of drug-induced hemolysis are anti-inflammatory medications, penicillins, and cephalosporins (eg, ceftriaxone). Although the mechanism of erythrocyte injury (eg, oxidative, complement mediated) varies depending on the medication, penicillins and cephalosporins typically cause hemolysis by binding to the erythrocyte surface, which creates a hapten for IgG attachment. Antibody-coated erythrocytes are then partially or wholly phagocytized by splenic macrophages, leading to extravascular hemolysis. Hemolysis is often associated with symptomatic anemia (eg, fatigue, pallor) and signs of hyperbilirubinemia (eg, jaundice, dark urine). Laboratory evaluation will typically reveal elevated indirect bilirubin (heme breakdown product), elevated lactate dehydrogenase (intracellular enzyme), reticulocytosis (increased immature RBCs), and lowered haptoglobin (binds free hemoglobin). The diagnosis is confirmed with the direct antiglobulin (Coombs) test, which detects IgG or C3 (a complement fragment) on the erythrocyte surface. Because hemolysis is triggered by the direct binding of the penicillin or cephalosporin to the erythrocyte membrane, cessation of the offending drug eliminates the antibody target and generally leads to complete resolution of symptoms within days. (Choice B) Anemia of chronic disease is caused by cytokine-mediated iron dysregulation. Although chronic infection (eg, viral hepatitis, tuberculosis) is a common trigger, anemia of chronic disease is gradual in onset and is not associated with hyperbilirubinemia (no RBC lysis). (Choice C) Certain antibiotics (eg, sulfa medications, chloramphenicol) are associated with myelosuppression. However, these medications generally cause pancytopenia, not isolated anemia; in addition, hyperbilirubinemia is not seen. (Choice D) Glucose-6-phosphate dehydrogenase (G6PD) deficiency is marked by hemolysis in the setting of oxidative stress due to infection, oxidizing medication, or oxidative foods. Although this patient has an infection, ceftriaxone is not an oxidizing medication. In addition, G6PD deficiency is X-linked; therefore, symptoms are less common in women. (Choice E) Severe infections can trigger disseminated intravascular coagulation, a consumptive coagulopathy associated with anemia due to erythrocyte injury from microvascular thrombi. However, these patients have prolonged coagulation times and thrombocytopenia. Educational objective: Penicillins and cephalosporins are common triggers for drug-induced hemolytic anemia because they can bind to the erythrocyte surface and act as haptens for IgG attachment. Subsequent clearance of IgG-coated erythrocytes by splenic macrophages leads to hemolytic anemia. Withdrawal of the offending drug usually leads to complete resolution of symptoms.

A 62-Year-Old Woman Is Being Evaluated for Worsening Anemia