活血化瘀法干预易栓症的临床疗效分析及一个遗传性易栓症家系的分子遗传学初步研究

发布时间：2018-04-02 09:33

  本文选题：易栓症　切入点：活血化瘀中药　出处：《广州中医药大学》2017年博士论文

【摘要】：目的:1.临床研究:回顾性分析试验组(失笑勇安汤加减联合华法林)及对照组(华法林)治疗反复下肢深静脉血栓形成或者合并其他部位深静脉栓塞的患者随访资料,探讨活血祛瘀法干预易栓症的临床疗效分析。2.实验研究:通过对岭南地区一汉族遗传性易栓症家系进行基因测序,明确此家系易栓症的的分子学诊断,找出基因突变点,为遗传性易栓症的靶向治疗提供依据。方法:1.临床研究:采用回顾性研究方法,通过查阅我院电子病历系统,收集全院出院诊断为"静脉栓塞性疾病"、"下肢深静脉血栓形成"、"肺栓塞、" "易栓症"和出院诊断中含有"栓塞"文字的患者,按照纳入标准和排除标准剔除不合格病例后,电话和门诊随访患者,采集患者的一般资料、各种检查结果、治疗方法等;筛选出符合本临床研究的病例42例,其中,试验组21例、对照组21例;试验组以失笑勇安汤加减联合华法林治疗(中药水煎服,每日一剂,分两次口服,每次250ml左右;华法林3mg qd),对照组以华法林治疗(3mgqd),并根据INR值调整华法林用量,观察时间为治疗4周后;比较试验组治疗前后、试验组及对照组治疗后指标差异,指标包括血小板计数(PLT)、血小板压积(PCT)、血小板分布宽度(PDW)、血小板平均体积(MPV)、大血小板比率(P-LCR)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、D-二聚体(DDI)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、血肌酐(CREA)、血尿素(UREA)、肿胀积分、疼痛积分;探讨活血祛瘀法干预易栓症的临床疗效分析。2.实验研究:导师组通过病例的收集工作,发现既往曾收治数名深静脉血栓栓塞性疾病患者具有家族聚集性,其家族中有9人都有反复发作的静脉血栓形成,且首发年龄较早,符合遗传性易栓症的诊断;采集该家系中3人血液(2名患者,1名正常人)进行凝血功能、PC活性、PS活性、AT-Ⅲ活性、HC-Ⅱ浓度等检测,并进行全基因组测序,试图寻找其发病的分子遗传学位点。结果:1.临床研究:纳入的42例病例经统计学分析,与治疗前比较,试验组治疗后血液分析指标(PLT、PCT、PDW、MPV、P-LCR)和凝血指标FIB显著下降(P0.05),凝血指标(PT、APTT)显著升高(P0.05),肝肾功能相关指标(ALT、AST、UREA、CREA)治疗前后差异不显著(P0.05),DDI和肿胀积分、疼痛积分显著降低(P0.05);对照组用药后 PLT、PT 显著升高(P0.05),PCT、PDW、MPV、P-LCR、APTT、FIB 和肝肾功能相关指标(ALT、AST、UREA、CREA)用药前后差异不显著(P0.05),DDI和疼痛积分和用药前相比差异不显著(P0.05),肿胀积分显著下降(P0.05)。治疗后组间比较,试验组和对照组血液分析指标(PLT、PCT、PDW、MPV、P-LCR)、凝血指标(PT、APTT、FIB)组间差异显著(P0.05);试验组和对照组肝功指标(ALT、AST)和肾功指标(UREA、CREA)组间差异不显著(P0.05);试验组和对照组DDI指标、肿胀积分、疼痛积分等组间差异显著(PO.05);试验组用药后血液分析指标(PLT、PCT、PDW、MPV、P-LCR)、FIB、DDI、肿胀积分、疼痛积分显著低于对照组,PT、APTT指标显著高于对照组。2.实验研究:结合家系图谱和所有检查结果分析,此遗传性易栓症家系属于常染色体显性遗传;根据全基因测序结果,找出3个与此病有关的突变基因,FII(c.C1504T:p.R502W、c.C1573T:p.R525W、c.C1621T:p.R541W)、MASP1(c.C1609G:p.H537D)的点突变可能通过激活凝血酶原,加速凝血过程而导致血栓形成;此家系患者病情反复,使用华法林效果欠佳,可能与CALU(c.383-387del:p.N128fs、c.386-390del:p.N129fs、c.839-843del:p.N280fs、c.617-621del:p.N206fs、c.863-867del:p.N288fs)的移码删除突变有关。结论:1.临床研究:通过此临床疗效分析发现,活血化瘀中药可改善易栓症患者的血小板参数、凝血指标、临床症状,且对肝肾功能损害较小,疗效优于单纯西药组。2.实验研究:通过全基因测序结果,寻找出此家系可能的致病基因为FII、MASP1,此家系使用华法林效果欠佳可能与CALU基因突变有关。
[Abstract]:Objective: 1. clinical research: a retrospective analysis of the experimental group (jiweishixiaosan Yongan decoction combined with Hua Falin) and control group (Hua Falin) for treatment of recurrent deep venous thrombosis of the lower limbs or patients with follow-up data from other parts of the deep venous thrombosis, experimental analysis of.2. clinical research on the effect of stasis intervention thrombophilia study: Based on south of the Five Ridges in a Han hereditary thrombophilia pedigree gene sequencing, clear this family to molecular diagnosis of thrombophilia, identify gene mutations, genetic thrombophilia targets provide the basis for treatment. Methods: 1. clinical research: by retrospective study, through access to electronic medical records system in our hospital. Collect hospital discharge diagnosis of venous thromboembolic disease "," deep vein thrombosis, pulmonary embolism, "" thrombophilia and discharge diagnosis contains "embolism" characters of patients, according to the inclusion and exclusion criteria excluding Unqualified cases, telephone and outpatient follow-up of patients with general information were collected, all inspection results, methods of treatment; selected 42 cases, one case of this clinical study, 21 cases of test group and 21 cases in the control group; experimental group in Shixiao Yongan decoction combined with warfarin therapy (Chinese medicine water decoction, a dose of daily orally two times, each time about 250ml; 3mg QD), warfarin warfarin treatment in the control group (3mgqd), and according to the INR value adjusted warfarin dosage for 4 weeks after treatment; compared the experimental group before and after treatment. The difference between the experimental group and control group after treatment indicators, including indicators the platelet count (PLT), plateletcrit (PCT), platelet distribution width (PDW), mean platelet volume (MPV), platelet large cell ratio (P-LCR), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), two D- dimer (DDI), valley transaminase (AL T), aspartate aminotransferase (AST), serum creatinine (CREA), blood urea (UREA), swelling score, pain score; clinical curative effect analysis of.2. experimental study of stasis intervention thrombophilia study: tutor group through the case collection, found previously treated patients with deep venous thromboembolic disease several veins with a family aggregation, the family had 9 people with recurrent venous thrombosis formation, and starting at an earlier age, consistent with the diagnosis of hereditary thrombophilia; collected 3 blood in this family (2 patients and 1 normal persons) of blood coagulation function, PC activity, PS activity, AT- activity. HC- II concentration detection, and whole genome sequencing, trying to find the molecular genetic pathogenesis degree. Results: 1. clinical study: 42 patients were included in the statistical analysis, compared with before treatment, experimental group after treatment, blood analysis index (PLT, PCT, PDW, MPV, P-LCR) and blood clotting index FIB 鏄捐憲涓嬮檷(P0.05),鍑濊��鎸囨爣(PT,APTT)鏄捐憲鍗囬珮(P0.05),鑲濊偩鍔熻兘鐩稿叧鎸囨爣(ALT,AST,UREA,CREA)娌荤枟鍓嶅悗宸�寮備笉鏄捐懀�

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