本文選題：易栓癥　切入點(diǎn)：活血化瘀中藥　出處：《廣州中醫(yī)藥大學(xué)》2017年博士論文

【摘要】：目的:1.臨床研究:回顧性分析試驗組(失笑勇安湯加減聯(lián)合華法林)及對照組(華法林)治療反復(fù)下肢深靜脈血栓形成或者合并其他部位深靜脈栓塞的患者隨訪資料,探討活血祛瘀法干預(yù)易栓癥的臨床療效分析。2.實驗研究:通過對嶺南地區(qū)一漢族遺傳性易栓癥家系進(jìn)行基因測序,明確此家系易栓癥的的分子學(xué)診斷,找出基因突變點(diǎn),為遺傳性易栓癥的靶向治療提供依據(jù)。方法:1.臨床研究:采用回顧性研究方法,通過查閱我院電子病歷系統(tǒng),收集全院出院診斷為"靜脈栓塞性疾病"、"下肢深靜脈血栓形成"、"肺栓塞、" "易栓癥"和出院診斷中含有"栓塞"文字的患者,按照納入標(biāo)準(zhǔn)和排除標(biāo)準(zhǔn)剔除不合格病例后,電話和門診隨訪患者,采集患者的一般資料、各種檢查結(jié)果、治療方法等;篩選出符合本臨床研究的病例42例,其中,試驗組21例、對照組21例;試驗組以失笑勇安湯加減聯(lián)合華法林治療(中藥水煎服,每日一劑,分兩次口服,每次250ml左右;華法林3mg qd),對照組以華法林治療(3mgqd),并根據(jù)INR值調(diào)整華法林用量,觀察時間為治療4周后;比較試驗組治療前后、試驗組及對照組治療后指標(biāo)差異,指標(biāo)包括血小板計數(shù)(PLT)、血小板壓積(PCT)、血小板分布寬度(PDW)、血小板平均體積(MPV)、大血小板比率(P-LCR)、凝血酶原時間(PT)、活化部分凝血活酶時間(APTT)、纖維蛋白原(FIB)、D-二聚體(DDI)、谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)、血肌酐(CREA)、血尿素(UREA)、腫脹積分、疼痛積分;探討活血祛瘀法干預(yù)易栓癥的臨床療效分析。2.實驗研究:導(dǎo)師組通過病例的收集工作,發(fā)現(xiàn)既往曾收治數(shù)名深靜脈血栓栓塞性疾病患者具有家族聚集性,其家族中有9人都有反復(fù)發(fā)作的靜脈血栓形成,且首發(fā)年齡較早,符合遺傳性易栓癥的診斷;采集該家系中3人血液(2名患者,1名正常人)進(jìn)行凝血功能、PC活性、PS活性、AT-Ⅲ活性、HC-Ⅱ濃度等檢測,并進(jìn)行全基因組測序,試圖尋找其發(fā)病的分子遺傳學(xué)位點(diǎn)。結(jié)果:1.臨床研究:納入的42例病例經(jīng)統(tǒng)計學(xué)分析,與治療前比較,試驗組治療后血液分析指標(biāo)(PLT、PCT、PDW、MPV、P-LCR)和凝血指標(biāo)FIB顯著下降(P0.05),凝血指標(biāo)(PT、APTT)顯著升高(P0.05),肝腎功能相關(guān)指標(biāo)(ALT、AST、UREA、CREA)治療前后差異不顯著(P0.05),DDI和腫脹積分、疼痛積分顯著降低(P0.05);對照組用藥后 PLT、PT 顯著升高(P0.05),PCT、PDW、MPV、P-LCR、APTT、FIB 和肝腎功能相關(guān)指標(biāo)(ALT、AST、UREA、CREA)用藥前后差異不顯著(P0.05),DDI和疼痛積分和用藥前相比差異不顯著(P0.05),腫脹積分顯著下降(P0.05)。治療后組間比較,試驗組和對照組血液分析指標(biāo)(PLT、PCT、PDW、MPV、P-LCR)、凝血指標(biāo)(PT、APTT、FIB)組間差異顯著(P0.05);試驗組和對照組肝功指標(biāo)(ALT、AST)和腎功指標(biāo)(UREA、CREA)組間差異不顯著(P0.05);試驗組和對照組DDI指標(biāo)、腫脹積分、疼痛積分等組間差異顯著(PO.05);試驗組用藥后血液分析指標(biāo)(PLT、PCT、PDW、MPV、P-LCR)、FIB、DDI、腫脹積分、疼痛積分顯著低于對照組,PT、APTT指標(biāo)顯著高于對照組。2.實驗研究:結(jié)合家系圖譜和所有檢查結(jié)果分析,此遺傳性易栓癥家系屬于常染色體顯性遺傳;根據(jù)全基因測序結(jié)果,找出3個與此病有關(guān)的突變基因,FII(c.C1504T:p.R502W、c.C1573T:p.R525W、c.C1621T:p.R541W)、MASP1(c.C1609G:p.H537D)的點(diǎn)突變可能通過激活凝血酶原,加速凝血過程而導(dǎo)致血栓形成;此家系患者病情反復(fù),使用華法林效果欠佳,可能與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)的移碼刪除突變有關(guān)。結(jié)論:1.臨床研究:通過此臨床療效分析發(fā)現(xiàn),活血化瘀中藥可改善易栓癥患者的血小板參數(shù)、凝血指標(biāo)、臨床癥狀,且對肝腎功能損害較小,療效優(yōu)于單純西藥組。2.實驗研究:通過全基因測序結(jié)果,尋找出此家系可能的致病基因為FII、MASP1,此家系使用華法林效果欠佳可能與CALU基因突變有關(guān)。
[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)娌葷枟鍓嶅悗宸紓涓嶆樉钁，

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