Xie Wenqing, Ma Kuifen, Xu Zhuoyun, Xie Jiao, Lu Xiaoyang, Wang Xiaojuan
Department of Clinical Pharmacy, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Kidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Transl Androl Urol. 2022 Oct;11(10):1410-1418. doi: 10.21037/tau-22-522.
Hypofibrinogenemia is a serious adverse reaction related to tigecycline administered against multidrug-resistant (MDR) bacteria and can lead to therapy termination. High dose and prolonged tigecycline therapy, renal failure, and base level of fibrinogen (FIB) were reported risk factors of tigecycline-associated FIB reduction. But results are unknown in patients with renal transplantation.
A single-center and a case-control study involving renal transplantation patients was conducted. From January, 2017 to January, 2020, patients with a tigecycline course more than 2 days and a baseline FIB level greater than 2 g/L were enrolled. Hypofibrinogenemia was defined as plasma FIB <2.0 g/L. The extent of FIB reduction was calculated based on the baseline of FIB level before tigecycline administration. FIBRO was defined as the extent of FIB reduction over 50%, and FIBRB referred to the extent of FIB reduction below 50%. Univariate and multivariate analyses were performed by logistic regression models to identify independent risk factors of tigecycline-associated FIB reduction.
In total, 120 patients were enrolled. A total of 114 patients (95.00%) developed with hypofibrinogenaemia. Hypofibrinogenemia mainly occurred 3 days after tigecycline administration. Of them, 79 (65.83%) developed FIBRO with a median occurrence of 3 [2-4] days after initiation of tigecycline. Multivariable regression analysis demonstrated that the FIB level before tigecycline use [odds ratio (OR): 3.225, 95% confidence interval (CI): 1.801-5.772] and total tigecycline dose (OR: 4.930, 95% CI: 1.433-16.959) were risk factors for FIBRO.
The FIB level before tigecycline use and total tigecycline dose were significantly associated with FIBRO, suggesting that FIB level and coagulation-related indicators should be closely monitored during tigecycline treatment to avoid life-threatening bleeding events.
低纤维蛋白原血症是与替加环素治疗多重耐药菌相关的严重不良反应，可导致治疗终止。高剂量及延长替加环素治疗、肾衰竭和纤维蛋白原（FIB）基础水平被报道为替加环素相关FIB降低的危险因素。但肾移植患者的情况尚不清楚。
进行了一项涉及肾移植患者的单中心病例对照研究。2017年1月至2020年1月，纳入接受替加环素治疗超过2天且基线FIB水平大于2g/L的患者。低纤维蛋白原血症定义为血浆FIB<2.0g/L。FIB降低程度根据替加环素给药前FIB水平基线计算。FIBRO定义为FIB降低超过50%的程度，FIBRB指FIB降低低于50%的程度。采用逻辑回归模型进行单因素和多因素分析，以确定替加环素相关FIB降低的独立危险因素。
共纳入120例患者。114例患者（95.00%）发生低纤维蛋白原血症。低纤维蛋白原血症主要发生在替加环素给药后3天。其中，79例（65.83%）发生FIBRO，中位发生时间为替加环素开始使用后3[2-4]天。多变量回归分析表明，替加环素使用前的FIB水平[比值比（OR）：3.225，95%置信区间（CI）：1.801-5.772]和替加环素总剂量（OR：4.930，95%CI：1.433-16.959）是FIBRO的危险因素。
替加环素使用前的FIB水平和替加环素总剂量与FIBRO显著相关，提示在替加环素治疗期间应密切监测FIB水平和凝血相关指标，以避免危及生命的出血事件。
