Case Presentation: A 60-year-old male with history of diabetes mellitus, right foot osteomyelitis, psoriasis, and multiple medication allergies (including vancomycin, levofloxacin, daptomycin, ertapenem, ampicillin-sulbactam, and infliximab) presented to the hospital with complaint of jaundice, abdominal pain, and vomiting. He had been diagnosed one week prior with methicillin sensitive Staphylococcus aureus septic arthritis and was being treated with intravenous ceftriaxone 2 grams daily for a 6-week course. Upon presentation, his labs revealed macrocytic anemia (hemoglobin 6.1g/dl) and evidence of hemolysis: elevated lactate dehydrogenase, reticulocyte count, and indirect bilirubin with decreased haptoglobin. A direct Coombs and Anti-C3 Coombs were positive and IgG Coombs test was negative. Peripheral blood smear showed reticulocytosis and bite cells as well as rare schistocytes. Hematology was consulted for possible drug induced immune hemolytic anemia secondary to Ceftriaxone. The patient was started on prednisone 1.5 mg/kg daily and Ceftriaxone was discontinued. Infectious disease recommended a switch to Linezolid and then Doxycycline for septic arthritis. Prednisone was continued until patient’s hemoglobin stabilized at 10 g/dL, at which time he was determined stable for discharge.
Discussion: Drug-induced immune hemolytic anemia (DIIHA) is a rare and often underdiagnosed condition occurring in 1 in 1,00,000 patients per year. The drugs frequently associated with DIIHA include cephalosporins, penicillins, nonsteroidal anti-inflammatory drugs, and quinine. At this time, ceftriaxone and cefotetan are the most commonly implicated. Reactions occur within a few days to two weeks after taking the drug and consist of formation of an immunogen which leads to complement activation and acute intravascular hemolysis. Laboratory data will show evidence of hemolysis as well as positive Direct Coombs and anti-C3 antisera. If DIIHA goes unrecognized, it can lead to severe, multiorgan involvement including shock, circulatory arrest, disseminated intravascular coagulation, and even death. The most important treatment measure in DIIHA is discontinuation of the offending drug. Steroids can be given but there is no direct evidence for steroid therapy at this time. DIIHA is an absolute contraindication for re-exposure to the offending medication, and drugs of the same class should be carefully considered before administration due to cross-reactivity.
Conclusions: Drug-induced immune hemolytic anemia is a rare syndrome that can be caused by medications commonly used in the hospital setting as in this case with Ceftriaxone. It is imperative for the internist to be aware of and monitor for this complication as failure to recognize DIHA can be severe and potentially fatal. Once recognized, providers must immediately discontinue the causative agent, document the reaction to avoid future exposure, and provide supportive care until stabilization of blood counts.