Cephalosporin-Associated Hypoprothrombinemia: Case and Review of the Literature

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Objective: To present a case of cefotetan-associated hypoprothrombinemia and to review the literature concerning cephalosporin-associated hypoprothrombinemia. Data Sources: Information was collected by conducting a MEDLINE search for cases, clinical trials, reviews, and other articles pertaining to cephalosporin use and the development of hypoprothrombinemia. Study Selection: Studies, cases, and letters were selected if they addressed the development of hypoprothrombinemia in cephalosporin-treated patients. Data Synthesis: A case of hypoprothrombinemia is described in an 82-year-old woman who received cefotetan for the treatment of a urinary tract infection. A review of the literature revealed more than 50 reported cases and multiple clinical studies evaluating this adverse effect. The postulated mechanism behind this occurrence is the inhibition of the synthesis of vitamin K-dependent clotting factors by the N-methyl-thiotetrazole (NMTT) moiety found in certain cephalosporin side chains. Risk factors associated with the development of this adverse effect include advanced age, renal and hepatic impairment, recent surgical procedures, malnutrition, and the use of H2-antagonists. Conclusions: Cephalosporins containing the NMTT side chain are associated with the development of hypoprothrombinemia and possibly bleeding, especially in high-risk patients.