溶栓后中性粒细胞升高与缺血性脑卒中早期神经功能恶化相关性研究
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摘要
目的探讨溶栓后中性粒细胞升高与缺血性脑卒中早期神经功能恶化(early neurological deterioration,END)发生的相关性。方法收集2017年1月—2018年11月的发病4.5 h内接受阿替普酶静脉溶栓治疗患者的临床资料。根据是否出现END,分为END组和非END组,观察两组患者溶栓前后中性粒细胞、淋巴细胞等指标的变化,以探讨基线及溶栓后中性粒细胞、淋巴细胞和中性粒细胞/淋巴细胞比率与END的相关性。结果共纳入患者187例,其中END组48例,非END组139例。溶栓前,两组患者除总蛋白(t=2.130,P=0.035)、白蛋白(t=2.777,P=0.007)外,其余指标比较差异均无统计学意义(P>0.05)。溶栓后,白细胞计数、中性粒细胞计数、中性粒细胞/淋巴细胞比值、纤维蛋白酶降解产物、基线和变化美国国立卫生研究院卒中量表评分、心源性脑卒中、责任血管狭窄程度及前循环皮质梗死部位,END组均高于非END组(P<0.05);而总蛋白、白蛋白、淋巴细胞计数、前白蛋白END组低于非END组(P<0.05)。溶栓前后,END组中性粒细胞增加明显(Z=-2.314,P=0.021)。中性粒细胞计数[比值比=1.288,95%置信区间(1.069,1.552)]为静脉溶栓END的独立影响因素之一;且预测END的特异度最高(灵敏度为62.5%,特异度为71.9%)。结论溶栓后中性粒细胞升高与END的发生有一定相关性。动态监测静脉溶栓治疗后的中性粒细胞可有助于预测END的发生。
Objective To explore the relevance of an increase in neutrophil count and early neurological deterioration(END) after intravenous thrombolysis in patients with acute ischemic stroke. Methods A retrospective study was conducted on the patients who received thrombolysis treatment of alteplase within 4.5 hours after onset between January 2017 and November 2018. Based on the existence of END, the patients were divided into the END group and the non-END group. Univariate and multivariate logistic regression, and receiver operating characteristic curves were used to analyze the relevances between END and the indexes such as neutrophil count, lymphocyte count, and neutrophil to lymphocyte ratio(NLR) after thrombolysis. Paired sample t test and Wilcoxon signed-rank test were used to compare the changes of neutrophil and lymphocyte before and after thrombolysis. Results A total of 187 patients were included,including 48 in the END group and 139 in the non-END group. Before thrombolysis, the differences of total protein(t=2.130, P=0.035) and albumin(t=2.777, P=0.007) between the two groups were statistically significant, but the differences in other clinical indexes between the two groups were not statistically significant(P>0.05). After thrombolysis,white blood cell count, neutrophil count, NLR, fibrinase degradation product, baseline and change of National Institute of Health Stroke Scale score, proportion of cardiogenic embolism, degree of responsible vascular stenosis and anterior circulation cortical infarction site were all higher in the END group than those in the non-END group(P<0.05). The total protein, albumin, lymphocyte count and prealbumin in the END group were lower than those in the non-END group(P<0.05). Neutrophil in the END group increased significantly(Z=-2.314, P=0.021) after thrombolysis. Neutrophil count[odds ratio=1.288, 95% confidence interval(1.069, 1.552)] was one of the independent influencing factors of venous thrombolysis END, and the specificity was the highest(the sensitivity was 62.5%, and the specificity was 71.9%).Conclusions After thrombolysis, elevated neutrophil count has some relevance to END. Dynamic monitoring on neutrophil count after intravenous thrombolysis treatment can predict the occurrence of END.
Objective To explore the relevance of an increase in neutrophil count and early neurological deterioration(END) after intravenous thrombolysis in patients with acute ischemic stroke. Methods A retrospective study was conducted on the patients who received thrombolysis treatment of alteplase within 4.5 hours after onset between January 2017 and November 2018. Based on the existence of END, the patients were divided into the END group and the non-END group. Univariate and multivariate logistic regression, and receiver operating characteristic curves were used to analyze the relevances between END and the indexes such as neutrophil count, lymphocyte count, and neutrophil to lymphocyte ratio(NLR) after thrombolysis. Paired sample t test and Wilcoxon signed-rank test were used to compare the changes of neutrophil and lymphocyte before and after thrombolysis. Results A total of 187 patients were included,including 48 in the END group and 139 in the non-END group. Before thrombolysis, the differences of total protein(t=2.130, P=0.035) and albumin(t=2.777, P=0.007) between the two groups were statistically significant, but the differences in other clinical indexes between the two groups were not statistically significant(P>0.05). After thrombolysis,white blood cell count, neutrophil count, NLR, fibrinase degradation product, baseline and change of National Institute of Health Stroke Scale score, proportion of cardiogenic embolism, degree of responsible vascular stenosis and anterior circulation cortical infarction site were all higher in the END group than those in the non-END group(P<0.05). The total protein, albumin, lymphocyte count and prealbumin in the END group were lower than those in the non-END group(P<0.05). Neutrophil in the END group increased significantly(Z=-2.314, P=0.021) after thrombolysis. Neutrophil count[odds ratio=1.288, 95% confidence interval(1.069, 1.552)] was one of the independent influencing factors of venous thrombolysis END, and the specificity was the highest(the sensitivity was 62.5%, and the specificity was 71.9%).Conclusions After thrombolysis, elevated neutrophil count has some relevance to END. Dynamic monitoring on neutrophil count after intravenous thrombolysis treatment can predict the occurrence of END.
引文
1Bluhmki E,Chamorro A,Dávalos A,et al.Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke(ECASSⅢ):additional outcomes and subgroup analysis of a randomised controlled trial.Lancet Neurol,2009,8(12):1095-1102.
2中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2014.中华神经科杂志,2015,48(4):246-257.
3Maestrini I,Strbian D,Gautier S,et al.Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes.Neurology,2015,85(16):1408-1416.
4Vidale S,Consoli A,Arnaboldi M,et al.Postischemic inflammation in acute stroke.J Clin Neurol,2017,13(1):1-9.
5Herz J,Sabellek P,Lane TE,et al.Role of neutrophils in exacerbation of brain injury after focal cerebral ischemia in hyperlipidemic mice.Stroke,2015,46(10):2916-2925.
6Awadh M,MacDougall N,Santosh C,et al.Early recurrent ischemic stroke complicating intravenous thrombolysis for stroke:incidence and association with atrial fibrillation.Stroke,2010,41(9):1990-1995.
7North American Symptomatic Carotid Endarterectomy Trial Collaborators,Barnett HJM,Taylor DW,et al.Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis.N Engl J med,1991,325(7):445-453.
8徐广会,王蕾,张仲,等.急性缺血性脑卒中患者静脉溶栓后早期神经功能恶化的研究.卒中与神经疾病,2018,25(4):394-397.
9崔颖.阿替普酶静脉溶栓治疗的急性缺血性卒中患者早期神经功能恶化的影响因素.河北:华北理工大学,2017.
10Murray KN,Girard S,Holmes WM,et al.Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia.Stroke,2014,45(11):3412-3419.
11Colasuonno M,Palange AL,Aid R,et al.Erythrocyte-inspired discoidal polymeric nanoconstructs carrying tissue plasminogen activator for the enhanced lysis of blood clots.ACS nano,2018,12(12):12224-12237.
12Kim J,Song TJ,Park JH,et al.Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction.Atherosclerosis,2012,222(2):464-467.
13朱慧,孟然,提衍丽,等.缺血性卒中急性期外周血白细胞动态变化观察.神经损伤与功能重建,2015,10(4):285-288.
14Akopov SE,Simonian NA.Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage.Stroke,1996,27(10):1739-1743.
15Shi J,Peng H,You S,et al.Increase in neutrophils after recombinant tissue plasminogen activator thrombolysis predicts poor functional outcome of ischaemic stroke:a longitudinal study.Eur J Neurol,2018,25(4):687-e45.
16Hyun YM,Hong CW.Deep insight into neutrophil trafficking in various organs.J Leukoc Biol,2017,102(3):617-629.
17Ruhnau J,Schulze J,Dressel A,et al.Thrombosis,neuroinflammation,and poststroke infection:the multifaceted role of neutrophils in stroke.J Immunol Res,2017:5140679.
18Macrez R,Ali C,Toutirais O,et al.Stroke and the immune system:from pathophysiology to new therapeutic strategies.Lancet Neurol,2011,10(5):471-480.
19Guo Z,Yu S,Xiao L,et al.Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke.J Neuroinflammation,2016,13(1):199.
2中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2014.中华神经科杂志,2015,48(4):246-257.
3Maestrini I,Strbian D,Gautier S,et al.Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes.Neurology,2015,85(16):1408-1416.
4Vidale S,Consoli A,Arnaboldi M,et al.Postischemic inflammation in acute stroke.J Clin Neurol,2017,13(1):1-9.
5Herz J,Sabellek P,Lane TE,et al.Role of neutrophils in exacerbation of brain injury after focal cerebral ischemia in hyperlipidemic mice.Stroke,2015,46(10):2916-2925.
6Awadh M,MacDougall N,Santosh C,et al.Early recurrent ischemic stroke complicating intravenous thrombolysis for stroke:incidence and association with atrial fibrillation.Stroke,2010,41(9):1990-1995.
7North American Symptomatic Carotid Endarterectomy Trial Collaborators,Barnett HJM,Taylor DW,et al.Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis.N Engl J med,1991,325(7):445-453.
8徐广会,王蕾,张仲,等.急性缺血性脑卒中患者静脉溶栓后早期神经功能恶化的研究.卒中与神经疾病,2018,25(4):394-397.
9崔颖.阿替普酶静脉溶栓治疗的急性缺血性卒中患者早期神经功能恶化的影响因素.河北:华北理工大学,2017.
10Murray KN,Girard S,Holmes WM,et al.Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia.Stroke,2014,45(11):3412-3419.
11Colasuonno M,Palange AL,Aid R,et al.Erythrocyte-inspired discoidal polymeric nanoconstructs carrying tissue plasminogen activator for the enhanced lysis of blood clots.ACS nano,2018,12(12):12224-12237.
12Kim J,Song TJ,Park JH,et al.Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction.Atherosclerosis,2012,222(2):464-467.
13朱慧,孟然,提衍丽,等.缺血性卒中急性期外周血白细胞动态变化观察.神经损伤与功能重建,2015,10(4):285-288.
14Akopov SE,Simonian NA.Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage.Stroke,1996,27(10):1739-1743.
15Shi J,Peng H,You S,et al.Increase in neutrophils after recombinant tissue plasminogen activator thrombolysis predicts poor functional outcome of ischaemic stroke:a longitudinal study.Eur J Neurol,2018,25(4):687-e45.
16Hyun YM,Hong CW.Deep insight into neutrophil trafficking in various organs.J Leukoc Biol,2017,102(3):617-629.
17Ruhnau J,Schulze J,Dressel A,et al.Thrombosis,neuroinflammation,and poststroke infection:the multifaceted role of neutrophils in stroke.J Immunol Res,2017:5140679.
18Macrez R,Ali C,Toutirais O,et al.Stroke and the immune system:from pathophysiology to new therapeutic strategies.Lancet Neurol,2011,10(5):471-480.
19Guo Z,Yu S,Xiao L,et al.Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke.J Neuroinflammation,2016,13(1):199.