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一项回顾性队列研究,评估肝硬化患者在使用头孢哌酮/舒巴坦时联合或不联合维生素 K1 补充的凝血功能变化。

A retrospective cohort study of coagulation function in patients with liver cirrhosis receiving cefoperazone/sulbactam with and without vitamin K1 supplementation.

机构信息

Department of Science and Technology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

出版信息

Int J Clin Pharm. 2024 Dec;46(6):1492-1499. doi: 10.1007/s11096-024-01796-w. Epub 2024 Sep 13.

Abstract

BACKGROUND

Cefoperazone/sulbactam is commonly prescribed for the treatment of infected patients with cirrhosis.

AIM

To investigate the effect of cefoperazone/sulbactam on coagulation in cirrhotic patients and assess the effectiveness of vitamin K1 supplementation in preventing cefoperazone/sulbactam-induced coagulation disorders.

METHOD

This retrospective cohort study compared coagulation function in 217 cirrhotic patients who received cefoperazone/sulbactam with and without vitamin K1 supplementation (vitamin K1 group, n = 108; non-vitamin K1 group, n = 109). Propensity score matching (PSM) was used to to reduce confounders' influence, the SHapley additive exPlanations (SHAP) model to explore the importance of each variable in coagulation disorders.

RESULTS

In the non-vitamin K1 group, the post-treatment prothrombin time (PT) was 16.5 ± 6.5 s and the activated partial thromboplastin time (aPTT) was 34.8 ± 9.4 s. These were significantly higher than pre-treatment values (PT: 14.6 ± 2.4 s, p = 0.005; aPTT: 30.4 ± 5.9 s, p < 0.001). In the vitamin K1 group, no differences were observed in PT, thrombin time, or platelet count, except for a slightly elevated post-treatment aPTT (37.0 ± 10.4 s) compared to that of pre-treatment (34.4 ± 7.2 s, p = 0.033). The vitamin K1 group exhibited a lower risk of PT prolongation (OR: 0.211, 95% CI: 0.047-0.678) and coagulation disorders (OR: 0.257, 95% CI: 0.126-0.499) compared to that of the non-vitamin K1 group. Propensity score matching analysis confirmed a reduced risk in the vitamin K1 group for prolonged PT (OR: 0.128, 95% CI: 0.007-0.754) and coagulation disorders (OR: 0.222, 95% CI: 0.076-0.575). Additionally, the vitamin K1 group exhibited lower incidences of PT prolongation, aPTT prolongation, bleeding, and coagulation dysfunction compared to the non-vitamin K1 group.

CONCLUSION

Cefoperazone/sulbactam use may be linked to a higher risk of PT prolongation and coagulation disorders in cirrhotic patients. Prophylactic use of vitamin K1 can effectively reduce the risk.

摘要

背景

头孢哌酮/舒巴坦常用于治疗合并肝硬化的感染患者。

目的

探讨头孢哌酮/舒巴坦对肝硬化患者凝血功能的影响,并评估维生素 K1 补充预防头孢哌酮/舒巴坦诱导的凝血障碍的效果。

方法

本回顾性队列研究比较了 217 例接受头孢哌酮/舒巴坦治疗的肝硬化患者的凝血功能,其中接受维生素 K1 补充(维生素 K1 组,n=108;非维生素 K1 组,n=109)。采用倾向评分匹配(PSM)减少混杂因素的影响,采用 SHapley 加法解释(SHAP)模型探索每个变量在凝血障碍中的重要性。

结果

在非维生素 K1 组中,治疗后凝血酶原时间(PT)为 16.5±6.5s,部分凝血活酶时间(aPTT)为 34.8±9.4s。与治疗前相比,这些值明显升高(PT:14.6±2.4s,p=0.005;aPTT:30.4±5.9s,p<0.001)。在维生素 K1 组中,PT、凝血酶时间和血小板计数无差异,除了治疗后 aPTT 略有升高(37.0±10.4s)外(34.4±7.2s,p=0.033)。与非维生素 K1 组相比,维生素 K1 组 PT 延长(OR:0.211,95%CI:0.047-0.678)和凝血障碍(OR:0.257,95%CI:0.126-0.499)的风险较低。倾向评分匹配分析证实,维生素 K1 组 PT 延长(OR:0.128,95%CI:0.007-0.754)和凝血障碍(OR:0.222,95%CI:0.076-0.575)的风险降低。此外,与非维生素 K1 组相比,维生素 K1 组 PT 延长、aPTT 延长、出血和凝血功能障碍的发生率较低。

结论

头孢哌酮/舒巴坦的使用可能与肝硬化患者 PT 延长和凝血障碍的风险增加有关。预防性使用维生素 K1 可有效降低风险。

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