Hypoprothrombinemia associated with cefmetazole

To report a case of hypoprothrombinemia associated with the use of cefmetazole sodium, define patients at risk for this adverse effect, and identify options to prevent this problem.

A malnourished patient with endstage renal disease received cefmetazole following a below-the-knee amputation of the right leg. Three days later, a prothrombin time (PT) and an international normalized ratio (INR) were obtained and were markedly elevated from baseline; however, the patient had no clinical symptoms of bleeding. Cefmetazole was discontinued. Vitamin K and fresh frozen plasma were administered. The PT and INR normalized within 24 hours and remained normal throughout the remainder of hospitalization.

The incidence of hypoprothrombinemia associated with cefmetazole reported in the literature is conflicting and not consistent. There are three proposed mechanisms of cephalosporin-associated hypoprothrombinemia, two of which involve the N-methylthiotetrazole (NMTT) chain. The most plausible mechanism is NMTT inhibition of vitamin K epoxide reductase in the liver. Patients at an increased risk for this adverse event include those with low vitamin K stores, specifically patients who are malnourished, with low albumin concentrations and poor food intake. The elderly and patients with liver or renal dysfunction are examples of populations at risk.

Hypoprothrombinemia may occur with cephalosporins and is especially problematic with those containing an NMTT side chain. Clinicians need to identify patients at risk for developing antibiotic-associated hypoprothrombinemia, monitor them closely, and give vitamin K as prophylaxis accordingly.