Grasela T H, Walawander C A, Welage L S, Wing P E, Scarafoni D J, Caldwell J W, Noguchi J K, Schentag J J
Pharmacoepidemiology Research Center, Millard Fillmore Hospital, Buffalo, New York.
Pharmacotherapy. 1989;9(3):158-64. doi: 10.1002/j.1875-9114.1989.tb04122.x.
N-methyl-thio-tetrazole (NMTT) has been proposed as a causative factor in antibiotic-associated coagulopathy. To evaluate this hypothesis, a nationwide surveillance program was initiated to determine the relative frequency of antibiotic-associated coagulopathy and the importance of specific risk factors. A total of 970 patients were studied, with 491 being treated for infections and 479 receiving antimicrobial surgical prophylaxis. The NMTT-containing antibiotic cefotetan was compared with non-NMTT-containing antibiotics, for example, cefoxitin and cefazolin (prophylaxis only), and an aminoglycoside-antianaerobic (AG + AA) combination. Prothrombin time (PT) and partial thromboplastin time (PTT) were measured for each patient prior to the start of antibiotics and within 24-96 hours after the conclusion of drug administration. The patient population was relatively young [mean (SD) age 51.0 (20) yrs] with good nutritional status. The overall frequency of hypoprothrombinemia (4.5%) and bleeding (1.7%) was very low, and was highest with the use of AG + AA (p less than 0.05). No statistical differences were observed for the remaining antibiotic regimens in either the prophylaxis or treatment group. Logistic regression analysis identified treatment with the AG + AA combination, presence of liver disease, and renal dysfunction as factors associated with an increased risk of hypoprothrombinemia. In conclusion, this study suggests that the frequency of antibiotic-associated coagulopathy is low, regardless of antibiotic, in patients who are not critically ill and not malnourished.
N-甲基硫代四唑（NMTT）被认为是抗生素相关性凝血病的一个致病因素。为评估这一假说，启动了一项全国性监测项目，以确定抗生素相关性凝血病的相对发生率以及特定危险因素的重要性。共研究了970例患者，其中491例接受感染治疗，479例接受抗菌手术预防用药。将含NMTT的抗生素头孢替坦与不含NMTT的抗生素（如头孢西丁和头孢唑林，仅用于预防）以及一种氨基糖苷类-抗厌氧菌（AG+AA）联合用药进行比较。在开始使用抗生素前以及用药结束后24 - 96小时内，对每位患者测量凝血酶原时间（PT）和部分凝血活酶时间（PTT）。患者群体相对年轻[平均（标准差）年龄51.0（20）岁]，营养状况良好。低凝血酶原血症的总体发生率（4.5%）和出血发生率（1.7%）非常低，使用AG+AA时发生率最高（p<0.05）。在预防组或治疗组中，其余抗生素治疗方案均未观察到统计学差异。逻辑回归分析确定，使用AG+AA联合用药、存在肝脏疾病和肾功能不全是与低凝血酶原血症风险增加相关的因素。总之，本研究表明，在病情不危急且无营养不良的患者中，无论使用何种抗生素，抗生素相关性凝血病的发生率都很低。
