The relationship between neutrophil elevation and early neurological deterioration after thrombolysis in patients with ischemic stroke_West China Medical Journal

Authors：

QIAN Xinyu ¹ , YANG Siyuan ² , Bilal Muhammad ² , DU Bo ¹ ,  GEN Deqin ¹

1. Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, P. R. China;
2. Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P. R. China;

Corresponding?author：

GEN Deqin, Email: gengdeqin@126.com

Keywords：

Acute ischemic stroke; Intravenous thrombolysis; Early neurological deterioration; Neutrophil count

DOI：

10.7507/1002-0179.201901147

Video：

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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.

Citation： QIAN Xinyu, YANG Siyuan, Bilal Muhammad, DU Bo, GEN Deqin. The relationship between neutrophil elevation and early neurological deterioration after thrombolysis in patients with ischemic stroke. West China Medical Journal, 2019, 34(6): 641-648. doi: 10.7507/1002-0179.201901147 Copy

1.	Bluhmki E, Chamorro A, Dávalos A, et al. Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke (ECASS Ⅲ): additional outcomes and subgroup analysis of a randomised controlled trial. Lancet Neurol, 2009, 8(12): 1095-1102.
2.	中華醫學會神經病學分會, 中華醫學會神經病學分會腦血管病學組. 中國急性缺血性腦卒中診治指南2014. 中華神經科雜志, 2015, 48(4): 246-257.
3.	Maestrini I, Strbian D, Gautier S, et al. Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neurology, 2015, 85(16): 1408-1416.
4.	Vidale S, Consoli A, Arnaboldi M, et al. Postischemic inflammation in acute stroke. J Clin Neurol, 2017, 13(1): 1-9.
5.	Herz 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.
6.	Awadh 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.
7.	North 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.	徐廣會, 王蕾, 張仲, 等. 急性缺血性腦卒中患者靜脈溶栓后早期神經功能惡化的研究. 卒中與神經疾病, 2018, 25(4): 394-397.
9.	崔穎. 阿替普酶靜脈溶栓治療的急性缺血性卒中患者早期神經功能惡化的影響因素. 河北: 華北理工大學, 2017.
10.	Murray 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.
11.	Colasuonno 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.
12.	Kim 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, 提衍麗, 等. 缺血性卒中急性期外周血白細胞動態變化觀察. 神經損傷與功能重建, 2015, 10(4): 285-288.
14.	Akopov 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.
15.	Shi 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.
16.	Hyun YM, Hong CW. Deep insight into neutrophil trafficking in various organs. J Leukoc Biol, 2017, 102(3): 617-629.
17.	Ruhnau J, Schulze J, Dressel A, et al. Thrombosis, neuroinflammation, and poststroke infection: the multifaceted role of neutrophils in stroke. J Immunol Res, 2017: 5140679.
18.	Macrez 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.
19.	Guo 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.

1. Bluhmki E, Chamorro A, Dávalos A, et al. Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke (ECASS Ⅲ): additional outcomes and subgroup analysis of a randomised controlled trial. Lancet Neurol, 2009, 8(12): 1095-1102.
2. 中華醫學會神經病學分會, 中華醫學會神經病學分會腦血管病學組. 中國急性缺血性腦卒中診治指南2014. 中華神經科雜志, 2015, 48(4): 246-257.
3. Maestrini I, Strbian D, Gautier S, et al. Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neurology, 2015, 85(16): 1408-1416.
4. Vidale S, Consoli A, Arnaboldi M, et al. Postischemic inflammation in acute stroke. J Clin Neurol, 2017, 13(1): 1-9.
5. Herz 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.
6. Awadh 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.
7. North 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. 徐廣會, 王蕾, 張仲, 等. 急性缺血性腦卒中患者靜脈溶栓后早期神經功能惡化的研究. 卒中與神經疾病, 2018, 25(4): 394-397.
9. 崔穎. 阿替普酶靜脈溶栓治療的急性缺血性卒中患者早期神經功能惡化的影響因素. 河北: 華北理工大學, 2017.
10. Murray 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.
11. Colasuonno 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.
12. Kim 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, 提衍麗, 等. 缺血性卒中急性期外周血白細胞動態變化觀察. 神經損傷與功能重建, 2015, 10(4): 285-288.
14. Akopov 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.
15. Shi 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.
16. Hyun YM, Hong CW. Deep insight into neutrophil trafficking in various organs. J Leukoc Biol, 2017, 102(3): 617-629.
17. Ruhnau J, Schulze J, Dressel A, et al. Thrombosis, neuroinflammation, and poststroke infection: the multifaceted role of neutrophils in stroke. J Immunol Res, 2017: 5140679.
18. Macrez 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.
19. Guo 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.

West China Medical Journal

The relationship between neutrophil elevation and early neurological deterioration after thrombolysis in patients with ischemic stroke

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