Breen G A, St Peter W L
Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, MN 55404, USA.
Ann Pharmacother. 1997 Feb;31(2):180-4. doi: 10.1177/106002809703100210.
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.
报告1例与使用头孢美唑钠相关的低凝血酶原血症病例，确定有发生这种不良反应风险的患者，并找出预防该问题的方法。
1例终末期肾病的营养不良患者在右下肢膝下截肢术后接受了头孢美唑治疗。3天后，检测凝血酶原时间（PT）和国际标准化比值（INR），结果较基线水平显著升高；然而，患者并无出血的临床症状。停用头孢美唑，并给予维生素K和新鲜冰冻血浆。PT和INR在24小时内恢复正常，且在住院的剩余时间内一直保持正常。
文献报道的与头孢美唑相关的低凝血酶原血症的发生率存在矛盾且不一致。头孢菌素相关低凝血酶原血症有三种提出的机制，其中两种涉及N-甲基硫代四唑（NMTT）链。最合理的机制是NMTT抑制肝脏中的维生素K环氧化物还原酶。发生这种不良事件风险增加的患者包括维生素K储备低的患者，特别是营养不良、白蛋白浓度低和食物摄入量少的患者。老年人以及肝或肾功能不全的患者就是有风险的人群。
头孢菌素可能会发生低凝血酶原血症，对于含有NMTT侧链的头孢菌素尤其成问题。临床医生需要识别有发生抗生素相关低凝血酶原血症风险的患者，密切监测他们，并相应地给予维生素K进行预防。
