尿激酶溶栓后出血及早期神经功能恶化危险因素的多中心研究

Risk factors for bleeding and early neurological deterioration after urokinase thrombolysis:a retrospective multicenter study

目的分析尿激酶溶栓治疗急性缺血性脑卒中(AIS)患者24 h内出血、早期神经功能恶化(END)的发生率及病死率;并进一步分析相关危险因素。方法选取2019年4月至2020年6月在云南省多个临床中心接受尿激酶和重组组织型纤溶酶原激活剂(rt-PA)溶栓治疗的AIS患者。尿激酶溶栓患者按起病至溶栓时间(OTT),即时间窗不同分为A组(OTT≤3 h)27例、B组(3 h<OTT≤4.5 h)57例、C组(4.5 h<OTT≤6 h)98例。采用χ^(2)检验比较尿激酶组和rt-PA组、尿激酶溶栓不同时间窗分组之间出血、END及病死率的差异,采用多因素Logistic回归分析法分析相关危险因素。结果共收集尿激酶溶栓患者182例,rt-PA溶栓患者414例。尿激酶组与rt-PA组相比,溶栓24 h内总出血率、颅内出血率、颅外出血率、症状性颅内出血(sICH)发生率、END发生率比较,差异均无统计学意义(P>0.05)。尿激酶溶栓A、B、C组总体出血风险[25.93%(7/27)vs 7.02%(4/57)vs 10.20%(10/98)]不同,差异具有统计学意义(χ^(2)=6.788,P=0.034),其中A组总体出血风险较B、C组高(χ^(2)=5.756、4.453,P=0.016、0.035);A、B、C组间颅内出血率、颅外出血率、END率比较,差异均无统计学意义(P>0.05)。OTT≤3 h(P=0.020,OR=3.899,95%CI:1.242~12.237)、白细胞计数升高(P=0.035,OR=1.177,95%CI:1.011~1.371)、心房颤动史(P=0.033,OR=4.775,95%CI:1.138~20.032)是溶栓24 h内出血的危险因素。凝血酶原时间(P=0.029,OR=0.484,95%CI:0.253~0.927)延长是溶栓后END的保护因素。结论6 h时间窗内给予尿激酶溶栓治疗AIS是安全的。OTT≤3 h、白细胞计数升高、心房颤动史是尿激酶溶栓24 h内出血的危险因素。凝血酶原时间延长是END的保护性因素。

Objective To analyze the incidence of bleeding,early neurological deterioration(END)and mortality within 24 hours among patients with the urokinase thrombolytic therapy after acute ischemic stroke(AIS),and to analyze the related risk factors.Methods The AIS patients were included who received urokinase and recombinant tissue plasminogen activator(rt-PA)thrombolytic therapy in eleven clinical centers in Yunan Province from April 2019 to June 2020.According to the thrombolytic time window,the patients who received urokinase thrombolytic therapy were divided into group A(onset to treatment time,OTT≤3 h,n=27),group B(3 h<OTT≤4.5 h,n=57)and group C(4.5 h<OTT≤6 h,n=98).The incidence of bleeding,END and the mortality between the urokinase group and rt-PA group and among urokinase subgroups were compared byχ^(2) test.The multivariate logistic regression was applied to analyze the possible risk factors.Results A total of 182 patients with urokinase treatment and 414 patients with rt-PA treatment were collected.There were no statistically significant differences in the incidence of total hemorrhage,intracranial hemorrhage,extracranial hemorrhage,symptomatic intracranial hemorrhage,and END between urokinase group and rt-PA group(P>0.05).The total hemorrhage incidence was different among the urokinase subgroups[group A:25.93%(7/27),group B:7.02%(4/57),group C:10.20%(10/98)],the total hemorrhage incidence of group A was significantly higher than group B and group C(χ2=5.756,4.453;P=0.016,0.035),and there were no statistically significant differences in the incidence of intracranial hemorrhage,extracranial hemorrhage and END among subgroups of urokinase(P>0.05).OTT≤3 h(P=0.020,OR=3.899,95% CI:1.242~12.237),leukocytosis(P=0.035,OR=1.177,95%CI:1.011~1.371)and atrial fibrillation(P=0.033,OR=4.775,95% CI=1.138~20.032)were risk factors for hemorrhage within 24 h after urokinase thrombolysis.The increase of prothrombin time(P=0.029,OR=0.484,95% CI:0.253~0.927)is a protective factor for the END.Conclusion Urokinase thrombolytic therapy within 6 h time window is safe.OTT≤3 h,leukocytosis and atrial fibrillation were risk factors for hemorrhage within 24 h after urokinase thrombolysis.The increase of prothrombin time is a protective factor for the END.