陈苑,张怡,张敏,恽文伟
CHEN Yuan,ZHANG Yi,ZHANG Min,YUN Wenwei

• 1:南京医科大学
• 2:南京医科大学附属常州市第二人民医院神经内科

摘要(Abstract)：

目的:探讨阿替普酶溶栓对缺血性脑卒中患者凝血功能及血液流变学的影响。方法:80例在溶栓时间窗内的缺血性脑卒中患者,行溶栓治疗的40例作为作为观察组,拒绝溶栓治疗的40例作为对照组;对照组患者给予阿司匹林治疗,观察组先给予阿替普酶溶栓治疗,复查头颅CT无出血后再给予阿司匹林治疗;于治疗前及治疗第10天时取血测定2组患者血浆纤维蛋白原(FIB)、凝血活酶时间(APTT)、凝血酶原时间(PT)及血小板(PLT)水平,测定血浆比黏度、全血高切黏度、红细胞聚集指数及血细胞容积;比较2组患者治疗第10天时脑出血、牙龈出血、皮疹或过敏、肝肾功能异常及血尿等并发症的发生率。结果:治疗前,2组患者PT、APTT、FIB、PLT、血浆比黏度、全血高切黏度、红细胞聚集指数及血细胞容积比较,差异无统计学意义(P>0.05);治疗第10天时,2组患者PT、APTT较治疗前延长,FIB、PLT、血浆比黏度、全血高切黏度、红细胞聚集指数及血细胞容积均较治疗前降低,观察组变化更显著,与对照组比较差异有统计学意义(P<0.05);治疗第10天时,2组患者脑出血、牙龈出血、皮疹或过敏、肝肾功能异常及血尿发生率比较,差异均无统计学意义(P>0.05)。结论:阿替普酶溶栓用于脑卒中患者有助于改善患者凝血功能及血液流变学指标。
Objective: To investigate the clinical effects of alteplase thrombolysis in patients with ischemic stroke and its effects on blood coagulation and hemorheology. Methods: Forty patients with ischemic stroke admitted to hospital for thrombolytic therapy from April 2015 to July 2018 were selected as the observation group, and 40 patients with similar onset time but refusing thrombolytic therapy were selected as the control group. Patients in both groups were treated within 4.5 hours after onset. The observation group was treated with alteplase first, and aspirin was given after reexamination of head CT without bleeding. The effects of the two groups were evaluated 10 days after treatment. The coagulation function, hemorheology index and complication rate were compared between the two groups. Results: The PT and APTT levels in the observation group were longer than those in the control group at 10 days after treatment(P<0.05). The FIB and PLT levels in the observation group were shorter than those in the control group(P<0.05). The plasma specific viscosity and whole blood were observed in the observation group 10 days after treatment. High-cut viscosity, erythrocyte aggregation index, blood cell volume, and fibrinogen levels were lower than those in the control group(P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05). Conclusion: The use of alteplase thrombolytic therapy in patients with stroke can improve the blood coagulation function and blood rheology, and reduced the incidence of complications.

关键词(KeyWords)： 阿替普酶;溶栓;阿司匹林;脑卒中;凝血功能;血液流变学;并发症
altiplase;thrombolysis;aspirin;stroke;coagulation;blood rheology;complications

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81471338)

作者(Author): 陈苑,张怡,张敏,恽文伟
CHEN Yuan,ZHANG Yi,ZHANG Min,YUN Wenwei

DOI: 10.19367/j.cnki.1000-2707.2019.11.020

参考文献(References)：

• [1] 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2018[J].中华神经科杂志,2018,51(9):666-682.
• [2] WANG W,JIANG B,SUN H,et al.Prevalence,incidence,and mortality of stroke in China:results from a nationwide population-based survey of 480 687 adults[J].circulation,2017,135(8):759-771.
• [3] ZHAO G,HUANG T,ZHENG M,et al.Comparative analysis on low- and standard-dose regimes of alteplase thrombolytic therapy for acute ischemic stroke:efficacy and safety[J].Eur Neurol,2018,79(1-2):68-73.
• [4] ZHAO G,HUANG T,ZHENG M,et al.Comparative analysis on low- and standard-dose regimes of alteplase thrombolytic therapy for acute ischemic stroke:efficacy and safety[J].European Neurology,2017,79(1-2):68.
• [5] 中国脑卒中医疗质量评估协作组.中国急性缺血性脑卒中治疗现状[J].中华神经科杂志,2009,42(4):223-228.
• [6] KENNEDY R,LEES ,JONATHAN E,et al.Effects of alteplase for acute stroke on the distribution of functional outcomes-a pooled analysis of 9 trials[J].Stroke,2016,47:2373-2379.
• [7] DEMAERSCHALK B M,KLEINDORFER D O,ADEOYE O M,et al.Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke:a statement for healthcare professionals from the american heart association/american stroke association[J].Stroke,2016,47(2):581-641.
• [8] SHEN B,LIU Q,GU Y,et al.Efficacy and safety evaluation on arterial thrombolysis in treating acute cerebral infarction[J].Cell Biochem Biophys,2015 73(2):297-304.
• [9] 刘泽霖.血栓形成机制中的相关进展[J].血栓与止血学,2019,25(1):1-3.
• [10]LU T,XIAN W,LIANG J,et al.Early changes in fibrinogen after administration of alteplase are associated with the short-term efficacy of thrombolysis[J].Medicine (Baltimore),2018,97(13):e0241.
• [11]Gurewich V.Therapeutic fibrinolysis:how efficacy and safety can be improved[J].J Am Coll Cardiol,2016,68(19):2099-2106.
• [12]LIAO X L,WANG C X,WANG Y L,et al.Implementation and outcome of thrombolysis with alteplase 3 to 4.5 h after acute stroke in Chinese patients[J].CNS Neurosci Ther,2013 ,19(1):43-47.
• [13]石瑜,许可,李可,等.阿替普酶联合常规治疗对脑梗死患者抗氧化能力、凝血功能及相关因子水平的影响[J].海南医学院学报,2018,24(24):2125-2128.
• [14]LIU M S,LIAO Y,LI G Q.Glomerular filtration rate is associated with hemorrhagic transformation in acute ischemic stroke patients without thrombolytic therapy[J].Chinese Medical Journal,2018,131(14):1639.
• [15]LU J,HU P,WEI G,et al.Effect of alteplase on platelet function and receptor expression[J].J Int Med Res,2019 ,47(4):1731-1739.
• [16]SAHER S,HASHEMSADEK M,HELMYNERVANA M,et al.Predictors of stroke outcome:the role of hemorheology,natural anticoagulants,and serum albumin[J].The Egyptian Journal of Neurology,Psychiatry and Neurosurgery,2018,54:18.
• [17]GURMAN P,MIRANDA O R,NATHAN A,et al.Recombinant tissue plasminogen activators (rtPA):a review[J].Clin Pharmacol Ther,2015,97(3):274-285.
• [18]CORREIA AS,MATIAS G,CALADO S,et al.Orolingual angiodema associated with alteplase treatment of acute stroke:a reappraisal[J].J Stroke Cerebrovasc Dis,2015,24(1):31-40.
• [19]BENTES C,MARTINS H,PERALTA A R,et al.Epileptic manifestations in stroke patients treated with intravenous alteplase[J].Eur J Neurol,2017,24(6):755-761.
• [20]FABRíCIO S,TUNA U,ALLEN C,et al.Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke[J].Blood,2017,129 (16):2280-2290.
• [21]KHATRI P,KLEINDORFER D O,DEVLIN T,et al.Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits:the prisms randomized clinical trial[J].JAMA,2018,320(2):156-166.
• [22]BERGE E,COHEN G,ROALDSEN M B,et al.Effects of alteplase on survival after ischaemic stroke (IST-3):3 year follow-up of a randomised,controlled,open-label trial[J].Lancet Neurol,2016,15(10):1028-1034.
• [23]KEPPLINGER J,BARLINN K,DECKERT S,et al.Safety and efficacy of thrombolysis in telestroke:a systematic review and meta-analysis[J].Neurology,2016,87(13):1344-1351.
• [24]苏敏,杨卫新,王万华,等.急性缺血性卒中重组组织型纤溶酶原激活剂静脉溶栓致出血性转化及其预后的危险因素分析[J].中华神经科杂志,2011,44(11):754-758.
• [25]尚俊英,李雪峰,赵虹,等.阿替普酶静脉溶栓治疗发病3～4.5 h急性脑梗死的疗效及安全性研究[J].临床与病理杂志,2016,36(12):1923-1927.

文章评论(Comment)：