阿加曲班联合硫酸氢氯吡格雷对急性后循环缺血性脑卒中患者凝血功能、NIHSS评分和BI指数的影响

目的 观察新型凝血酶抑制剂阿加曲班联合抗血小板药硫酸氢氯吡格雷对急性后循环缺血性脑卒中患者血液高凝状态、血小板（PLT）计数、美国国立卫生研究院卒中量表（NIHSS）评分和Barthel指数（BI）的影响。方法 回顾性选取2020年9月-2021年8月揭阳市人民医院神经内科诊治的急性后循环缺血性脑卒中患者70例为研究对象，根据治疗方法分为对照组和试验组，每组各35例，两组患者的血压、血糖都严格依照急性缺血性脑卒中治疗指南予以监测管理，同时使用稳定斑块等药物。对照组口服硫酸氢氯吡格雷片，每次75 mg，每天1次，持续服用14 d。试验组在对照组基础上加用阿加曲班注射液，在开始治疗的第1~2天，阿加曲班注射液60 mg加入至0.9%氯化钠注射液380 mL中，输液泵泵入，24 h持续不间断静脉输注，从第3天起，阿加曲班注射液10 mg加入至0.9%氯化钠注射液250 mL中，输液泵泵入，持续3 h静脉输注，间隔12 h再输注1次，持续用药5 d，阿加曲班注射液共用药7 d。采用NIHSS评分评估两组患者的神经缺损程度，采用BI指数评估两组患者日常生活自理能力。动态检测两组患者凝血三项凝血酶时间（TT）、凝血酶原时间（PT）、活化部分凝血酶原时间（APTT）]和血小板计数（PLT）。观察记录用药过程中两组患者不良反应发生情况。结果 治疗14 d，试验组总有效率91.43%，对照组总有效率68.57%，两组比较差异有统计学意义（P<0.05）。治疗前，两组患者NIHSS评分及BI指数比较，差异无统计学意义（P>0.05）。治疗后两组患者NIHSS评分均较治疗前明显降低（P<0.05），且治疗后试验组NIHSS评分显著低于对照组（P<0.05）；治疗后两组患者BI指数均较治疗前明显升高（P<0.05），且治疗后试验组BI指数显著高于对照组（P<0.05）。与用药前和对照组相比，试验组在应用阿加曲班注射液第1天（60 mg·d^-1），TT、PT、APTT均明显延长（P<0.05）；用药第3天，即减量为20 mg·d^-1，TT、PT、APTT较用药第1天均明显缩短（P<0.05），但较治疗前和对照组有所延长（P<0.05）；停药第2天，TT、PT、APTT均恢复至治疗前水平。PLT在阿加曲班注射液用药前、用药期间（60 mg·d^-1、20 mg·d^-1）、停药后无明显变化，差异无统计学意义（P>0.05）。对照组凝血三项和PLT在各检测时间点均无明显变化，差异无统计学意义（P>0.05）。两组患者在治疗期间未发生过敏性休克、出血、心律失常等与治疗药物相关的不良反应。结论 阿加曲班注射液联合硫酸氢氯吡格雷能够有效抑制血栓形成而不影响正常的凝血功能，明显改善急性后循环缺血性脑卒中患者的高凝状态，抗血栓再次形成能力强，安全性好；患者神经功能缺损情况明显改善，日常独立生活能力得到提高，病情得到有效控制。阿加曲班注射液联合硫酸氢氯吡格雷是一种有效的治疗急性后循环缺血性脑卒中方法，有较高的临床推广应用价值。

Effects of argatroban combined with clopidogrel bisulfate on coagulation function, NIHSS score and BI in patients with acute posterior circulation ischemic stroke

Objective To observe the effects of new thrombin inhibitor argatroban combined with antiplatelet drug clopidogrel bisulfate on blood hypercoagulability, platelet (PLT) count, National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) in patients with acute posterior circulation ischemic stroke. Methods A total of 70 patients with acute posterior circulation ischemic stroke treated in the Department of Neurology of Jieyang People''s Hospital from September 2020 to August 2021 were selected retrospectively. According to the treatment method, they were divided into control group and experimental group, with 35 cases in each group. Blood glucose was monitored and managed in strict accordance with the guidelines for the treatment of acute ischemic stroke, and drugs such as plaque stabilization were used at the same time. Patients in the control group were took Clopidogrel Bisulfate Tablets orally, 75 mg each time, once a day for 14 days. Patients in the experimental group were added with Argatroban Injection on the basis of the control group. On the first to second days of treatment, 60 mg of Argatroban Injection was added to 380 mL of 0.9% sodium chloride injection, pumped by infusion pump and continuously infused intravenously for 24 h. From the third day, 10 mg of Argatroban Injection was added to 250 mL of 0.9% sodium chloride injection, pumped by infusion pump and continuously infused intravenously for three hours, another infusion was given at an interval of 12 h for five days, and agatroban shared the drug for seven days. NIHSS score was used to evaluate the degree of nerve defect of patients in the two groups, and BI was used to evaluate the self-care ability of daily life of patients in the two groups. Three coagulation itemsthrombin time (TT), prothrombin time (PT), activated partial prothrombin time (APTT)] and platelet (PLT) counts were dynamically measured in the two groups. The adverse reactions of the two groups were observed and recorded. Results After 14 d of treatment, the total effective rate was 91.43% in the experimental group and 68.57% in the control group. There was significant difference between the two groups (P < 0.05). Before treatment, there was no significant difference in NIHSS score and BI between the two groups (P > 0.05). The NIHSS score of the two groups after treatment was significantly lower than that before treatment (P < 0.05), and the NIHSS score of the experimental group was significantly lower than that of the control group (P < 0.05). After treatment, the BI of the two groups was significantly higher than that before treatment (P < 0.05), and the BI of the experimental group was significantly higher than that of the control group (P < 0.05). Compared with the pre-medication and control group, TT, PT and APTT in the experimental group were significantly prolonged on the first day (Argatroban Injection 60 mg·d^-1) (P < 0.05). On the third day of treatment (Argatroban Injection 20 mg·d^-1), TT, PT and APTT were significantly shorter than those on the first day of treatment (P < 0.05), but longer than those before treatment and the control group (P < 0.05). On the second day after drug withdrawal, TT, PT and APTT returned to the level before treatment. There was no significant change in PLT count before and during argatroban treatment and after drug withdrawal (P > 0.05). In the control group, there was no significant change in the three items of coagulation and PLT count at each detection time point, and the difference was not statistically significant (P > 0.05). There were no adverse reactions related to therapeutic drugs, such as anaphylactic shock, bleeding, arrhythmia and so on. Conclusion Argatroban combined with clopidogrel bisulfate can effectively inhibit thrombosis without affecting the normal coagulation function, significantly improve the hypercoagulable state of patients with acute posterior circulation ischemic stroke, have strong antithrombosis ability and good safety. Argatroban combined with clopidogrel bisulfate is an effective method for the treatment of acute posterior circulation ischemic stroke, which has high clinical application value.