【摘要】 背景替罗非班作为糖蛋白Ⅱb/Ⅲa（GPⅡb/Ⅲa）受体拮抗剂,已被用于急性缺血性脑血管疾病的临床治疗中。然而,静脉溶栓治疗后早期使用替罗非班是否增加穿支动脉梗死患者的出血风险,能否改善患者临床结局,目前尚缺乏足够的临床研究证据。目的分析替罗非班治疗经阿替普酶静脉溶栓治疗后神经功能恶化的穿支动脉梗死患者的疗效及安全性,以期为患者提供更加安全有效的治疗方案,从而改善患者预后。方法本研究为回顾性研究。选取2017年1月—2020年1月于安康市中心医院神经内科及卒中急救中心住院的经阿替普酶静脉溶栓治疗后神经功能恶化的穿支动脉梗死患者37例为研究对象。所有患者于发病4.5 h内接受标准剂量的注射用阿替普酶静脉溶栓治疗。根据患者阿替普酶静脉溶栓治疗后出现神经功能恶化时是否使用替罗非班,分为对照组（n=18）及试验组（n=19）。对照组常规给予硫酸氢氯吡格雷+阿司匹林肠溶片抗血小板聚集治疗21 d。试验组给予替罗非班(前3 min按5μg/kg的剂量静脉注射,之后以0.075μg·kg^-1·min^-1的剂量持续泵入24 h)治疗,在替罗非班治疗结束前4 h予以硫酸氢氯吡格雷+阿司匹林肠溶片口服,重叠抗血小板聚集治疗21 d。比较患者入院时与阿替普酶静脉溶栓治疗后1 h美国国立卫生研究院卒中量表（NIHSS）评分及两组不同时间点（入院时、阿替普酶静脉溶栓治疗后1 h、神经功能恶化时和阿替普酶静脉溶栓治疗后第7、30、90天）NIHSS评分,阿替普酶静脉溶栓治疗后第90天神经功能恢复情况,阿替普酶静脉溶栓治疗前、治疗后48 h凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原（FBG）,阿替普酶静脉溶栓治疗后48 h血小板减少症发生情况,发病48 h内神经功能持续恶化情况,替罗非班治疗结束后第1天或第2天症状性颅内出血发生情况,治疗期间血尿或便血发生情况。结果 37例患者阿替普酶静脉溶栓治疗后1 h NIHSS评分低于入院时NIHSS评分（P<0.05）。治疗方法与时间在NIHSS评分上不存在交互作用（P>0.05）;治疗方法在NIHSS评分上主效应不显著（P>0.05）;时间在NIHSS评分上主效应显著（P<0.05）。两组阿替普酶静脉溶栓治疗后第90天神经功能良好者所占比例比较,差异无统计学意义（P>0.05）。阿替普酶静脉溶栓治疗后48 h,两组PT、APTT比较,差异无统计学意义（P>0.05）;阿替普酶静脉溶栓治疗后48 h,试验组FBG高于对照组（P<0.05）。阿替普酶静脉溶栓治疗后48 h,试验组有1例患者发生血小板减少症,对照组无一例患者发生血小板减少症。两组患者均无发生症状性颅内出血、尿血或便血。结论对于穿支动脉梗死患者,在阿替普酶静脉溶栓治疗后出现神经功能恶化后早期给予替罗非班治疗的安全性较好,但尚未发现其可改善患者神经功能。更多还原

【Abstract】 Background Tirofiban,a GP Ⅱ b/Ⅲ a receptor antagonist,has been used in the clinical treatment of acute ischemic cerebrovascular disease.However,whether the early use of tirofiban after intravenous thrombolytic therapy increases the risk of bleeding in patients with perforating artery infarction,and whether it can improve the clinical outcome of patients,there is still insufficient clinical research evidence.Objective To analyze the efficacy and safety of tirofiban in the treatment of perforating artery infarction patients with neurological deterioration after intravenous thrombolytic therapy with alteplase,so as to provide more safe and effective treatment for patients,thereby improving the prognosis of patients. Methods This study is a retrospective study.37 patients with perforating artery infarction after alteplase intravenous thrombolytic therapy in the Department of Neurology and Stroke Emergency Center of Ankang Central Hospital from January 2017 to January 2020 were selected.All patients received standard dose of alteplase intravenous thrombolytic therapy within 4.5 h of onset.Patients were divided into control group（n=18）and experimental group（n=19）according to whether they used tirofiban when their neurological function deteriorated after alteplase intravenous thrombolysis therapy.The control group was routinely given clopidogrel bisulfate+aspirin enteric-coated tablets for anti-platelet aggregation treatment for 21 days.The experimental group was given tirofiban(5 μg/kg intravenous injection in the first 3 minutes,followed by continuous pumping at a dose of 0.075 μg·kg^-1·min^-1 for 24 h)treatment,and clopidogrel bisulfate+aspirin enteric-coated tablets were given orally 4 h before the end of tirofiban treatment,and overlapped with antiplatelet aggregation therapy for 21 days.The NIHSS scores of patients were compared at admission and 1 h after alteplase intravenous thrombolysis therapy,the incidence of thrombocytopenia 48 h after alteplase intravenous thrombolysis therapy,the continuous deterioration of neurological function within 48 h after onset,the occurrence of symptomatic intracranial hemorrhage on the 1 st or 2 nd day after the end of tirofiban treatment and the occurrence of hematuria or hematochezia during treatment were compared between the two groups.Results The NIHSS score of 37 patients were significantly reduced at 1 h after alteplase intravenous thrombolytic therapy compared with at admission（P<0.05）.There was no interaction between treatment method and time on NIHSS score（P>0.05）.And the main effect of treatment method was not significant on NIHSS score（P>0.05）,but the main effect of time was significant on NIHSS score（P<0.05）.The NIHSS scores of the control group and the experimental group at 1 h after alteplase intravenous thrombolysis therapy were lower than those at admission,respectively（P<0.05）.There was no significant difference in the percentage of patients with good neurological function at 90 days after alteplase intravenous thrombolysis therapy between the two groups（P>0.05）.There was no significant difference in PT and APTT between the two groups 48 h after alteplase intravenous thrombolysis therapy（P>0.05）;FBG in the experimental group was higher than that in the control group 48 h after alteplase intravenous thrombolysis therapy（P<0.05）.48 h after alteplase intravenous thrombolysis therapy,thrombocytopenia occurred in one patient in the experimental group,and no thrombocytopenia occurred in the control group.No symptomatic cerebral hemorrhage,hematuria or hematochezia occurred in the two groups.Conclusion For patients with perforator artery infarction,early treatment with tirofiban after alteplase intravenous thrombolytic therapy has a good safety,but it has not been found that tirofiban can improve the neurological function of patients更多还原