Graduate School of Life Science, Hokkaido University, Kita 10-Jo, Nishi 8-Chome, Kita-Ku, Sapporo, 060-0810, Japan.
Department of Pharmacy, Hokkaido University Hospital, Kita 14-Jo, Nishi 5-Chome, Kita-Ku, Sapporo, 060-8648, Japan.
Eur J Clin Pharmacol. 2023 Mar;79(3):415-425. doi: 10.1007/s00228-023-03455-x. Epub 2023 Jan 30.
Thrombocytopenia is a major event associated with linezolid (LZD) therapy. Factors affecting LZD-induced thrombocytopenia (LIT) have been reported in previous studies. However, several issues pertaining to LIT have not yet been clarified. In the present study, we used Japanese big data to investigate associated factors and their high-risk combinations that influence LIT.
Patients administered LZD between May 2006 and October 2020 were included in this study. LIT was defined as either a 30% or more reduction from the baseline platelets or platelet values of < 100,000/µL. We evaluated factors affecting LIT and combinations of factors that alter LIT risk according to a decision tree (DT) analysis, a typical machine learning method.
We successfully enrolled 1399 patients and LIT occurred in 44.7% of the patients (n = 626). We classified the laboratory data on renal function, LZD duration, age, and body weight (BW) into smaller categories. The results of multivariate analysis showed that prolonged LZD therapy, BW < 45 kg, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m, and dialysis were risk factors for LIT. The DT analysis revealed that the highest risk was a combination of LZD duration ≥ 14 days and eGFR < 30 mL/min/1.73 m.
The present study extracted four risk factors and identified high-risk combinations for LIT. Patients with these risk factors should be closely monitored.
血小板减少症是与利奈唑胺(LZD)治疗相关的主要事件。先前的研究已经报道了影响 LZD 诱导的血小板减少症(LIT)的因素。然而,关于 LIT 的几个问题尚未得到澄清。在本研究中,我们使用日本大数据调查了影响 LIT 的相关因素及其高危组合。
本研究纳入了 2006 年 5 月至 2020 年 10 月期间接受 LZD 治疗的患者。LIT 定义为基线血小板减少 30%或以上,或血小板值<100,000/μL。我们根据决策树(DT)分析评估了影响 LIT 的因素以及改变 LIT 风险的因素组合,这是一种典型的机器学习方法。
我们成功纳入了 1399 例患者,其中 44.7%(n=626)发生了 LIT。我们将肾功能、LZD 持续时间、年龄和体重(BW)的实验室数据分为更小的类别。多变量分析结果表明,LZD 治疗时间延长、BW<45kg、估计肾小球滤过率(eGFR)<30mL/min/1.73m 和透析是 LIT 的危险因素。DT 分析显示,LZD 持续时间≥14 天和 eGFR<30mL/min/1.73m 的组合风险最高。
本研究提取了四个 LIT 的危险因素,并确定了高危组合。具有这些危险因素的患者应密切监测。