凝血功能异常在血小板减少导致脓毒性休克患者死亡中的作用

Role of coagulation dysfunction in thrombocytopenia-related death in patients with septic shock

目的探讨血小板减少对脓毒性休克患者预后的影响及其介导死亡的机制。方法采用回顾性病例对照研究,选择2015年4月1日至2023年1月31日北京大学人民医院急诊重症监护病房(ICU)、综合ICU收治的脓毒性休克患者。根据入ICU 24 h内血小板最低值是否小于100×109/L将患者分为血小板减少组和非血小板减少组。结局指标为ICU病死率。比较两组患者的基线资料、住院信息及实验室检查结果,通过Logistic回归分析患者住院死亡的危险因素,并对回归分析结果使用Bootstrap法进行中介效应分析。结果共纳入301例脓毒性休克患者,其中172例(57.1%)出现血小板减少,129例(42.9%)未出现血小板减少。两组患者在年龄、病死率、出现弥散性血管内凝血(DIC)、肾脏替代治疗、肌酐、尿素氮、总胆红素、白细胞计数、淋巴细胞计数、凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)等方面差异具有统计学意义。单因素Logistic回归分析显示,血小板减少〔优势比(OR)=4.478〕、肾脏替代治疗(OR=4.601)、DIC(OR=6.248)、肌酐(OR=1.005)、尿素氮(OR=1.126)、总胆红素(OR=1.006)及PT(OR=1.126)是脓毒性休克患者住院死亡的危险因素(均P<0.05)。多因素Logistic回归分析显示,血小板减少〔OR=3.338,95%可信区间(95%CI)为1.910~5.834,P=0.000〕、肾脏替代治疗(OR=3.175,95%CI为1.576~6.395,P=0.001)及PT(OR=1.077,95%CI为1.011~1.147,P=0.021)为脓毒性休克患者住院死亡的独立危险因素。中介分析显示,在脓毒性休克患者血小板减少导致死亡的过程中,51%是由于发生凝血功能障碍导致的。结论血小板减少是脓毒性休克患者死亡强有力的预测因子,半数患者的死亡可能是由于出现凝血功能异常导致。

Objective To explore the effect of thrombocytopenia on the prognosis of patients with septic shock and its mechanism in leading to death.Methods A retrospective case-control study was conducted.Patients with septic shock admitted to emergency intensive care unit(EICU)and intensive care unit(ICU)in Peking University People's Hospital from April 1,2015 to January 31,2023 were enrolled.Patients were divided into the thrombocytopenia group and the non-thrombocytopenia group,according to whether the minimum platelet count was less than 100×109/L within 24 hours after admission to ICU.The outcome index was the mortality during ICU stay.The baseline data,hospitalization information and laboratory test results of the two groups were compared,and the risk factors of in-hospital death were analyzed by Logistic regression,and the mediation effect was performed by Bootstrap method.Results A total of 301 patients with septic shock were enrolled,of which 172(57.1%)had thrombocytopenia and 129(42.9%)did not.There were significant differences between the two groups in age,mortality,disseminated intravascular coagulation(DIC),continuous renal replacement therapy,and level of creatinine,urea nitrogen,total bilirubin,white blood cell count,lymphocyte count,prothrombin time(PT)and activated partial thromboplastin time(APTT).Univariate Logistic regression analysis showed thrombocytopenia[odds ratio(OR)=4.478],continuous renal replacement therapy(OR=4.601),DIC(OR=6.248),serum creatinine(OR=1.005),urea nitrogen(OR=1.126),total bilirubin(OR=1.006)and PT(OR=1.126)were risk factors of death during hospitalization in patients with septic shock(all P<0.05).Multivariate Logistic regression analysis showed that thrombocytopenia[OR=3.338,95%confidence interval(95%CI)was 1.910-5.834,P=0.000],continuous renal replacement therapy(OR=3.175,95%CI was 1.576-6.395,P=0.001)and PT(OR=1.077,95%CI was 1.011-1.147,P=0.021)were independent risk factors for in-hospital mortality in patients with septic shock.Mediation analysis showed that 51%of the deaths due to thrombocytopenia in patients with septic shock were due to coagulopathy.Conclusions Thrombocytopenia is a powerful predictor of death in septic shock patients,and half of all thrombocytopenia-related deaths may be due to abnormal coagulation function.