Cefazolin-induced hemolytic anemia: a case report and systematic review of literature

Abstract

Background Cefazolin is a first-generation cephalosporin commonly used for skin and soft tissue infections, abdominal and orthopedic surgery prophylaxis, and methicillin-sensitive staph aureus. Cephalosporins as a whole are known potential inducers of hemolytic anemia; however, mechanism of action is primarily autoimmune, and compared to other drugs, cefazolin is the least common. Methods A rare case report of cefazolin-induced hemolytic anemia “CIHA” and a systematic review of CIHA articles in English literature. Two authors performed review of publications and articles were selected based on inclusion and exclusion criteria. A systematic search of the literature yielded 768 entries with five case reports on cefazolin-induced hemolytic anemia. Case presentation/results An 80-year-old female with methicillin-sensitive Staphylococcus aureus “MSSA” endocarditis. The patient was started on intravenous “IV” cefazolin that that resulted in hemolytic anemia and eosinophilia. Switching to vancomycin improved hemoglobin level and resolved eosinophilia. Four cefazolin-induced hemolytic anemia case reports and one population-based article with a case reported were analyzed with respect to direct antiglobulin test “DAT” (also known as the direct Coombs test) results, prior penicillin sensitivity, and acute anemia causes exclusion. Conclusions CIHA is a rare cause of clinically significant anemia. The diagnosis of drug-induced anemia is one of exclusion. It is important to consider DAT results and prior penicillin sensitivity when evaluating a patient for cefazolin-induced hemolytic anemia. However, the frequency of cefazolin use and resultant anemia necessitates early recognition of hemolytic anemia and prompt discontinuation of cefazolin, especially with long-term use.

Clinical-Pathological Conference Series from the Medical University of Graz

“…This leaves drug-induced or toxic causes on the list of differential diagnoses. About 125 different drugs have been identified to potentially cause hemolytic anemia with NSAIDs and anti-cancer drugs being the most prevalent [ 26 , 27 ]. Neither medication was taken by our patient; however, about 6 weeks earlier he had been on a cephalosporin for 5 days.…”

“…Neither medication was taken by our patient; however, about 6 weeks earlier he had been on a cephalosporin for 5 days. Indeed, cephalosporins are known to be potential inducers of clinically significant hemolytic anemia [ 27 – 30 ].…”

“…Drug-induced hemolytic anemia usually occurs within days or weeks of exposure to a drug and may be immune-mediated or nonimmune-mediated (oxidant injury). In case of immune-mediated hemolytic anemia, Coombs test (direct antiglobulin test) tends to be positive with IgG or complement activating drug dependent-antibodies of mainly IgM-type (immune complex type hemolytic anemia) attached to the surface of red blood cells [ 27 , 29 ]. The molecular mechanism of cephalosporin-induced hemolytic anemia is still poorly understood, but an immune-mediated process is suggested, even though varying degrees of direct antiglobulin test activity have been reported in affected patients [ 27 ].…”

“…In case of immune-mediated hemolytic anemia, Coombs test (direct antiglobulin test) tends to be positive with IgG or complement activating drug dependent-antibodies of mainly IgM-type (immune complex type hemolytic anemia) attached to the surface of red blood cells [ 27 , 29 ]. The molecular mechanism of cephalosporin-induced hemolytic anemia is still poorly understood, but an immune-mediated process is suggested, even though varying degrees of direct antiglobulin test activity have been reported in affected patients [ 27 ]. In view of the constellation of a negative Coombs test and a period of 6 weeks between termination of cephalosporin treatment and onset of symptoms, drug-induced hemolytic anemia does not seem to be the underlying cause of the patient’s complaints.…”

Vancomycin-Induced Hemolytic Anemia

“…Drug-induced immune hemolytic anemia (DIIHA) is a rare but well-known cause of hemolytic anemia [ 1 ]. The number of medications known to cause DIIHA has expanded over the last few years; therefore, a high index of clinical suspicions is required to make the diagnosis.…”