Correlation Analysis Of Serum Bilirubin With Hemorrhagic Transformation And Clinical Outcomes Of Acute Ischemic Stroke After Intravenous Thrombolysis

Objective:The present study aimed to evaluate the correlation analysis of serum bilirubin with hemorrhagic transformation(HT)and clinical outcomes of acute ischemic stroke after intravenous thrombolysis.Methods:From June 2018 to November 2021,we consecutively recruited 420 patients who suffered from acute ischemic stroke within 6 hr from the symptoms onset and received intravenous thrombolysis in our green channel of emergency stroke.All patients underwent post-thrombolysis brain computed tomography(CT)scan or magnetic resonance imaging(MRI)study within 24 hr.Depending on whether hemorrhagic transformation occurred or not,acute ischemic stroke patients were divided into two groups,the hemorrhagic transformation group(HT group)and the no-hemorrhagic transformation group(no-HT group).We obtained clinical data of acute ischemic stroke patients on admission and compared the data among patients between two groups.Multivariate logistic regression analysis was used to estimate the relationship between serum bilirubin and hemorrhagic transformation.Clinical outcomes at discharge was assessed according to the modified Rankin Scale(mRS)score.Multivariate logistic regression analysis was used to estimate the relationship between bilirubin and clinical prognosis.If serum bilirubin is an independent risk factor for hemorrhagic transformation and poor prognosis,the Receiver Operating Characteristic(ROC)curve was used to analyze the predictive value of serum bilirubin for hemorrhagic transformation and poor prognosis of acute ischemic stroke patients after thrombolysis.Results:1.Baseline dataIn this study,a total of 420 acute ischemic stroke patients were included.The median age was 66(56,74)years,and 277(66%)of patients were men.A total of 58(13.8%)patients suffered from hemorrhagic transformation.25(6.0%)had symptomatic intracranial hemorrhage(sICH).2.Single factor and multivariate logistic regression and ROC analysis of hemorrhage transformation after intravenous thrombolysisHT Group and no-HT group after intravenous thrombolysis were compared,age,NIHSS score at admission,atrial fibrillation,transient ischemic attack(TIA)or history of stroke,severe stenosis or occlusion of large blood vessels,white blood cell,neutrophil,random blood glucose,AST,direct bilirubin,indirect bilirubin,total bilirubin were significantly different between the two groups(P<0.05).Then,adjustment for other variables,the NIHSS score at admission(OR=1.091,95%CI=1.041～1.142,P=0.002),severe stenosis or occlusion of large blood vessels(OR=2.542,95%CI=1.322～4.888,P=0.005),white blood cell count(OR=1.139,95%CI=1.045～1.240,P=0.003),neutrophil count(OR=1.100,95%CI=1.013～1.195,P=0.024)indirect bilirubin(OR=1.130,95%CI=1.072～1.191,P<0.001),total bilirubin(OR=1.097,95%CI=1.049～1.146,P<0.001)were independently associated with the hemorrhagic transformation.Based on the ROC curve,when the cut-off value of indirect bilirubin in serum was 9.20,the sensitivity of predicting hemorrhage transformation after intravenous thrombolysis in acute ischemic stroke was 0.810,the specificity was 0.517,and the area under the ROC curve was 0.701(95%CI:0.628～0.774,P<0.001).When the cut-off value of total bilirubin was 15.65,the sensitivity of predicting hemorrhage transformation after thrombolysis was 0.552,the specificity was 0.785,and the area under the ROC curve was 0.705(95%CI:0.633～0.778,P<0.001).3.Single factor and multivariate logistic regression and ROC analysis of clinical outcomes after intravenous thrombolysisFavourable prognosis groups and poor prognosis groups after intravenous thrombolysis were compared,age,NIHSS score at admission,atrial fibrillation,TIA or history of stroke,severe stenosis or occlusion of large blood vessels,hemorrhage transformation,symptomatic intracranial hemorrhage(sICH),white blood cell,neutrophil,AST,direct bilirubin,indirect bilirubin,total bilirubin were significantly different between the two groups(P<0.05).Then,adjustment for other variables,the NIHSS score at admission(OR=1.112,95%CI=1.071～1.154,P<0.001),severe stenosis or occlusion of large blood vessels(OR=2.126,95%CI=1.338～3.376,P=0.001),white blood cell(OR=1.224,95%CI=1.123～1.133,P<0.001),neutrophil(OR=1.224,95%CI=1.122～1.336,P<0.001),indirect bilirubin(OR=1.058,95%CI=1.014～1.104,P=0.009),direct bilirubin(OR=1.236,95%CI=1.055～1.449,P=0.009),total bilirubin(OR=1.054,95%CI=1.017～1.092,P=0.004)were independently associated with the poor prognosis(P<0.05).Based on the ROC curve,when the cut-off value of indirect bilirubin was 7.75,the sensitivity of predicting poor prognosis after intravenous thrombolysis in acute ischemic stroke is was 0.741,the specificity was 0.442,and the area under the ROC curve was 0.603(95%CI:0.549～0.658,P<0.001).When the cut-off value of total bilirubin in serum was 2.15,the sensitivity of predicting poor prognosis after thrombolysis in acute ischemic stroke was 0.778,the specificity was 0.416,and the area under the ROC curve was 0.629(95%CI:0.576～0.682,P<0.001).When the cut-off value of total bilirubin in serum was 12.65,the sensitivity of predicting poor prognosis after thrombolysis in acute ischemic stroke was 0.593,the specificity was 0.602,and the area under the ROC curve was 0.621(95%CI:0.568～0.675,P<0.001).Conclusion:Higher serum indirect bilirubin and total bilirubin may predict hemorrhagic transformation after intravenous thrombolysis in acute ischemic stroke patients,direct bilirubin was an independent risk factor of hemorrhagic transformation;High serum indirect bilirubin,direct bilirubin and total bilirubin are independent risk factors for clinical outcomes after intravenous thrombolysis in acute ischemic stroke.