中国汉族人群的遗传性活化蛋白C抵抗症遗传特点观察

目的:研究中国汉族遗传性易栓症家系的遗传基础,探索汉族人群的遗传性活化蛋白C抵抗(Resistance ofactivated protein C,APCR)症遗传特点。方法:通过临床检查和家系调查,分析该家系发病的分子基础。结果:易栓症相关基因(FV)第10号外显子均不存在FVLeiden突变。但发现存在FVrs6020A-G纯合突变。结论:该遗传性APCR症家系中排除了FVLeiden突变,提示APCR存在遗传异质性;发现了FVrs6020A-G纯合突变,提示在中国汉族人群中存在与APCR相关新的FV基因突变。     

新疆地区动脉血栓形成患者抗活化蛋白C及FV Leiden突变的调查

目的研究抗活化蛋白C（activated protein C resistance，APCR）现象和FV Leiden在新疆正常人群、血栓患者中的发生情况。方法对414例正常体检者（N）和79例脑梗死患者组（CT）及46例心肌梗死患者组（MI），用APCR法进行APCR敏感比（n—APC—SR）（〈0．68）和APCR阳性率（〈2．0为阳性）测定，用多聚酶链反应-限制性内切酶长度多态性（PCR—RFLP）分析及DNA序列分析对以上标本APCR阳性者做FV Leiden突变和凝血酶原G20210A位基因突变的检测的分析。结果APCR发生率正常对照组为6．28％，其APCR发生率在哈萨克族、维吾尔族、回族、汉族中分别是12％、8．4％、8．35％及4．8％，正常人APCR发生率在哈萨克族较高，且各少数名族与汉族APCR发生率差异有统计学意义（P〈0．05）。脑梗死病例组的APCR发生率为11．39％，心肌梗死病例组的APCR发生率为8．70％；两组间以及两组APCR发生率分别与对照组比较差异有统计学意义（P〈0．05）。各组人群中均未检出FV Leiden 1691 G—A突变杂合子以及凝血酶原G20210A位基因突变。结论APCR现象在新疆地区正常人少数民族中有较高的发生率，其分布与人种、地域有关。未检出FV Leiden，和凝血酶原G20210A位突变。因此，FV Leiden突变不是新疆地区人群动脉血栓发病的主要危险因素.     

动脉血栓性疾病抗活化蛋白C和凝血因子Ⅴ基因突变的研究

引起动脉血栓形成的病因很多,其中抗活化蛋白C现象是至今所知的最主要的原因,APCR是到目前为止人们所发现的发生率最高的血栓风险因素,APCR和FⅤ Leiden存在地区种属差异。本文主要就动脉血栓形成与APCR进行综述。     

系统性红斑狼疮患者获得性活化蛋白C抵抗现象与抗磷脂抗体的检测

目的：通过检测系统性红斑狼疮（SLE）患者获得性活化蛋白C抵抗（APCR）和抗磷脂抗体的发生率,探讨APCR与SLE患者血栓形成的相关性,以及SLE患者血栓形成中,APCR与抗磷脂抗体的相关性。方法：采用APC－APTT法,dRVVT-LA法,ELISA法及PCR－酶切法分别对30例SLE患者和30例正常对照进行APCR及狼疮抗凝物,抗心磷脂抗体和FV Leiden突变检测,结果：SLE病人APCR阳性率（14／30,46．67％）明显高于正常对照组（1／30,3．3％,P＜0．005）,SLE患者无一例FV Leiden突变。APCR阳性患者中血栓发生率（6／14,42．85％）明显高于APCR阴性患者（1／16,6．25％,P＜0．05）,狼疮抗凝物阳性患者中血栓发生率（6／12,50％）明显高于其阴性患者（2／18,11．1％,P＜0．05）,结论：获得性APCR和狼疮抗凝物均是SLE患者合并血栓形成的危险因素之一,但获得性APCR的发生与抗磷脂抗体的存在无关,表明获得性APCR的发生并非抗磷脂抗体抑制蛋白C通路导致凝血异常及致血栓形成的唯一途径。     

系统性红斑狼疮患者获得性活化蛋白C抵抗现象与抗磷脂抗体的检测

目的 :通过检测系统性红斑狼疮 (SLE)患者获得性活化蛋白C抵抗 (APCR)和抗磷脂抗体的发生率 ,探讨APCR与SLE患者血栓形成的相关性 ,以及SLE患者血栓形成中 ,APCR与抗磷脂抗体的相关性。方法 :采用APC -APTT法 ,dRVVT -LA法 ,ELISA法及PCR_酶切法分别对 30例SLE患者和 30例正常对照进行APCR及狼疮抗凝物 ,抗心磷脂抗体和FVLeiden突变检测。结果 :SLE病人APCR阳性率 (14/30 ,46 .6 7% )明显高于正常对照组 (1/30 ,3.3% ,P <0 .0 0 5 )。SLE患者无一例FVLeiden突变。APCR阳性患者中血栓发生率 (6 /14,42 .85 % )明显高于APCR阴性患者 (1/16 ,6 .2 5 % ,P<0 .0 5 )。狼疮抗凝物阳性患者中血栓发生率 (6 /12 ,5 0 % )明显高于其阴性患者 (2 /18,11.1% ,P <0 .0 5 )。结论 :获得性APCR和狼疮抗凝物均是SLE患者合并血栓形成的危险因素之一 ,但获得性APCR的发生与抗磷脂抗体的存在无关 ,表明获得性APCR的发生并非抗磷脂抗体抑制蛋白C通路导致凝血异常及致血栓形成的唯一途径。     

Activated protein C resistance in antiphospholipid thrombosis syndrome

Objective To explore the correlation between antiphospholipid antibodies (APA)，activated protein C resistance (APCR) and antiphospholipid thrombosis (APL-T) syndrome and further investigate the mechanism of thrombosis in APL-T syndrome. Methods ELISA, PTT-LA and APTT±APC methods were used to detect anticardiolipin antibodies (ACA), lupus anticoagulants (LA) and APC R in 20 APL-T syndrome patients. Results Twenty patients were diagnosed as APL-T. ACA-IgG,M and LA are strongly associated with APL-T. The incidence of APCR in APL-T(75%) was significantly higher than that of the normal group (5%). Conclusion There was high prevalence of APCR in APL-T, which was strongly associated with LA. It is proposed that acquired APCR induced by APA is a key to understanding thrombosis in Chinese APL-T patients.     

汉族人深静脉血栓形成患者FV Leiden突变检测

目的 ;探讨汉族人FV基因 16 91位点多态分布情况及FVLeiden突变与深静脉血栓形成的关系。方法 :利用聚合酶链反应和限制性片段长度多态性 (PCR RFLP)方法 ,检测 10 3例深静脉血栓形成 (DVT)患者与 10 6例正常对照的FVLeiden突变 ,并进行对比分析。结果 :2组FV基因第 16 91位点的基因型为G/G ,全部为野生型 ,未见突变类型。结论 :FVLeiden突变作为汉族人深静脉血栓形成的主要危险因素的可能性极小     

EFFECTS OF ANTICOAGULATION PROTEIN DEFECT IN MATERNAL PLASMA ON SPONTANEOUS ABORTION

Objective To investigate the mechanism of anticoagulation protein defect in the pathogenesis of unexplained recurrent miscarriage.Methods Fifty-seven patients with a history of unexplained abortion were enrolled as the investigation group for tests of protein C, protein S, antithrombin Ⅲ (AT-Ⅲ), as well as activated protein C resistance (APC-R). The control group consisted of fifty healthy women with a history of hormal pregnancy and delivery. Blood samples were obtained for measuring serum activity of protein C, protein S, AT- Ⅲ, and APC-R. Patients with positive APC-R were tested for factor Ⅴ (FV) Leiden gene mutation by PCR-RFLP method.Results Of the 57 patients, 12 (21.1%), 1 (1.8%), and 5 (8.8%) cases were found with protein S, protein C, and AT-Ⅲdeficiency respectively, and 13 (22.8%) cases with positive results of APC-R. Of the control group, no protein C or AT-Ⅲdeficiency was ever found, whereas 2 (4.0%) volunteers were presented with protein S deficiency and 3 (6.0%) with positive results of APC-R. No FV Leiden gene mutation was identified in all the patients with positive APC-R results. Late spontaneous abortion cases had higher incidence of anticoagulation protein defect than the early cases.Conclusion Anticoagulation protein defect may play a role in the pathogenesis of fetal loss, especially for those occurring in late stage of pregnancy.     

下肢深静脉血栓形成患者血浆抗凝蛋白水平检测的临床意义

目的：探讨下肢深静脉血栓形成（LDVT）患者的发病机制，研究抗凝血酶（AT）、蛋白S（PS）、蛋白C（PC）、活化蛋白C抵抗性（APCR）在LDVT患者中的变化。方法：用ACL Puturn 型全自动血凝仪检测LDVT患者100例（初发、复发患者各73、27例）和健康者100例的AT、PS、PC活性及APCR。结果：LDVT组与正常对照组相比，LDVT复发组与初发组相比，AT、PS、PC活性明显降低，APCR阳性率明显升高,差异有统计学意义（P＜0.01～0.001）；100例LDVT患者中，25例有抗凝蛋白缺陷，以PS缺陷的总发生率最高,占13%(13例),其次是PC缺陷,占8%(8例)，AT缺陷占5%(5例)，APCR缺陷的总发生率最小，占4%（4例）。结论：先天性或获得性抗凝蛋白缺陷是LDVT发病和复发的重要机制之一。     

Prevalence of factor V Leiden in a Canadian blood donor population.

OBJECTIVE: To determine the prevalence of factor V Leiden in a Canadian blood donor population. DESIGN: Cross-sectional laboratory study. SETTING: Hamilton Centre of the Canadian Red Cross Society. PARTICIPANTS: Volunteer donors who attended Hamilton Centre blood donor clinics over a 4-day period in August 1994; blood samples from 356 people were evaluable. OUTCOME MEASURES: Presence of factor V Leiden. RESULTS: Factor V Leiden was detected in 19 of the 356 people, for a prevalence rate of 5.3% (95% confidence interval 3.0% to 7.6%). All 19 people were shown to be heterozygous for the mutation. CONCLUSION: Factor V Leiden is common in the Canadian population. Its prevalence is similar to that reported in other Western countries. These data are relevant in the clinical management of patients at risk for venous thrombosis and those with recurrent thrombotic disorders.     

习惯性流产与抗活化的蛋白C的研究

目的:了解抗活化的蛋白C(APC)在习惯性流产(RSA)患者中的发生情况,并进一步探讨APCR引起胎盘血管微小血栓形成并进而引起RSA的发生机制。方法:采用APC-KPTT法,ELISA法和PTT-LA法分别对16例RSA及20例正常对照(NC)进行APCR、抗心磷脂抗体(ACA)和狼疮抗凝物(LA)检测,采用一期法检恻FVⅦ:C,胶乳凝集法检测D-Dimer。结果:16例RSA患者共8例抗磷脂抗体(APA)阳性,其中4例LA阳性,2例ACA阳性,2例LA、ACA同时阳性,阳性率(50%)明显高于NC组(0/20)(P<0.005),APCR阳性率为50％,明显高于NC组(5%)(P<0.005)。APA阳性组APCR阳性率(87.5%)明显高于NC组(5%)(P<0.005)FVⅡ:C及D-Dimer阳性率均明显高于NC组(P<0.001及P<0.05)。APA阴性组APCR阳性率(12.5%)与NC组无显著性差异(P>0.05)FVⅡ:C明显高于NC组(P0.05),相关分析显示,APA阳性组APCR发生率(87.5％)明显高于地APA阴性组(12.5%)(P<0.005)。结论:习惯性流产患者胎盘血管发生血栓一方面由于患者体内处于高凝状态,另一方面由于APCR在习惯性流产患者中有较高的发生率且与APA有明显相关性,APCR可能是引起胎盘微血栓形成并引起习惯性流产的主要原因之一。     

Factor V Leiden: who should be tested?

Resistance to activated protein C resulting from the genetic point mutation known as factor V Leiden is the most frequently found genetic risk factor associated with familial predisposition to venous thrombosis. Factor V Leiden is also frequent among people with nonfamilial venous thrombosis and appears to have a relatively high prevalence rate in the general population. The author comments on the findings of the first Canadian prevalence study of factor V Leiden, reported in this issue by Dr. David H. Lee and associates (see pages 285 to 289). She notes that although certain hereditary and clinical variables are known to modulate the risk of venous thrombosis in people with factor V Leiden, explanations for the relatively high prevalence of this mutation and the wide spectrum of risk associated with it are still speculative. Management guidelines for affected patients are quickly evolving but are still limited by a lack of clinical data. It is clear that further research into factor V Leiden will have considerable importance for the understanding and management of thrombotic risk.     

狼疮性肾炎抗活化蛋白C的测定及意义

目的 :探讨抗磷脂抗体和抗活化蛋白C(APCR)与狼疮性肾炎 (LN)的关系及APCR的可能形成原因。方法 :检测 33例LN和 37例无LN的系统性红班狼疮 (NLN) ,ELISA检测ACA -IgG、IgM、IgA、PTT -LA检测LA ,APTT±APC检测APCR。结果 :LN组APCR阳性率 5 7 6% ,明显高于NLN组 ( 32 4% ) ;LN组ACA(IgG、IgM )阳性率 42 4% ,明显高于NLN组 ( 18 9% ) ;APCR和IgG -ACA同时阳性LN的发生率 ( 7/ 7)明显高于APCR阳性而IgG -ACA阴性者( 12 / 2 4)。结论 :APCR和ACA在LN有较高的发生率 ,ACA引起的获得性APCR可能是LN的发病机制之一。     

补肾祛瘀汤治疗血栓性疾病30例临床观察

目的观察补肾祛瘀汤对血栓性疾病患者血清内皮素（ET）、一氧化氮（NO）、活化蛋白C抗体（APCR）的影响。方法将60例血栓性疾病患者随机分为治疗组和对照组，每组各30例。两组患者在急性期均使用肠溶阿司匹林抗栓治疗，治疗组口服补肾祛瘀汤，对照组用尿激酶静脉滴注治疗，比较两组治疗前后上述指标数值的变化。结果两组治疗后ET及APCR均降低（P〈0．05）、NO均升高（P〈0．05），治疗组与对照组比较，有统计学意义（P（0．05）。结论补肾祛瘀汤在治疗血栓性疾病时有降低ET、APCR，升高NO的作用。     

2种新的凝血因子V基因突变导致的遗传性凝血因子V缺乏症

目的 对一个遗传性凝血因子V缺乏症家系进行凝血因子V（FV）基因突变的检测。方法 经用活化部分凝血活酶时间（APTT）,凝血酶原时间（PT）及FV促凝活性（FV：C）和FV抗原（FV：Ag)测定进行表型诊断;用PCR法对先证者（女,16岁）的FV基因25个外显子及其侧翼序列进行扩增。PCR产物纯化后直接测序,检测其基因突变。突变位点经限制笥内切酶分析证实。108名健康献血者作对照。结果 先证者APTT126.6s,PT42.8s,FV:C0.3%;FV:Ag1.3%,FⅡ：C,FVⅡ：C,FVⅢ：C,FIX：C,FX：C和Fbg均在正常范围内：FV外显子区共发现5个与GeneBankZ99572序列不同的位点,其中突变位点为位于第8外显子区的G1348T和位于第14外显子区的4887-8delG。家系分析表明前导致先证者FV缺乏的原因。这是2个导致遗传性FV缺乏症的新的FV基因突变位点。     

子痫前期产妇与易栓症的相关研究

目的通过对子痫前期妇女、正常妊娠妇女及存在活化蛋白C抵抗(APCR)现象的子痫前期患者血液中凝血、抗凝血指标的测定,观察子痫前期产妇女与易栓症的关系。方法取子痫前期妇女30例作为研究对象(其中轻度子痫前期15例,重度子痫前期15例),正常妊娠妇女40例作为对照,正常非妊娠妇女20例测定活化蛋白C比率(APCr),作为APCR阳性的判定标准。取外周静脉血4ml,其中2ml应用血球计数仪获取红细胞比积(HCT)、血小板(PLT)、纤维蛋白原(Fbg)值;1.8ml应用血凝仪获取活化部分凝血活酶时间(aPTT)、加入活化蛋白C(APC)后的aPTT值,对以上指标进行统计学分析。结果重度子痫前期组外周血HCT、PLT、Fbg水平、aPTT时间分别为35.51±3.56%、178.87±81.66×109/L、3.68±0.98g/L、33.83±4.77s;轻度子痫前期组为33.15±2.64%、179.60±59.85×109/L、3.83±0.70g/L、32.00±3.51s;正常妊娠组为33.65±2.92%、194.98±62.01×109/L、3.91±0.77g/L、31.70±2.56s。HCT及Fbg水平在子痫前期APCR阳性组中分别为36.80±3.25%、4.52±0.74g/L;在APCR阴性组中为33.71±3.38%、3.57±0.77g/L。HCT水平重度子痫前期组较正常妊娠组及轻度子痫前期组高;aPTT在重度子痫前期组较正常妊娠组延长。子痫前期APCR阳性组中,HCT及Fbg值均比APCR阴性组高,差异有统计学意义(P0.05)。结果子痫前期孕妇血液呈血栓前状态,这种状态以APCR阳性的子痫前期最为明显。     

Thrombophilia in young patients with acute myocardial infarction

OBJECTIVE: To investigate the association of thrombophilia and coronary artery disease (CAD) in patients with myocardial infarction (MI). METHODS: Under the age of 45 years, 129 patients with MI and 107 control subjects were included into the study. Traditional risk factors of CAD and protein C, S, antithrombin III deficiencies, factor V Leiden (FV Leiden), prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated. RESULTS: There were statistically significant differences in terms of obesity, smoking, triglyceride, total cholesterol, high-density lipoprotein, high-density lipoprotein, and very-low-density lipoprotein cholesterol, family history, hypertension, diabetes, and left ventricular hypertrophy between patients and controls. None of the patients and controls had protein C, protein S, and antithrombin III deficiencies. Ten patients (7.8%) and 4 controls (3.7%) had heterozygote FV Leiden mutation. Homozygous prothrombine G20210A gene mutation was detected in one patient (1.1%). Homozygous MTHFR C677T mutation was observed in 7.8% (patients) and in 6.5% (controls). Heterozygous MTHFR C677T mutation was detected 36.4% in patients and 31.7% in controls. The difference was not statistically significant in terms of carriage of thrombophilic mutations. CONCLUSION: We found that traditional risk factors increased the risk of CAD. Prothrombin G20210A, FV Leiden and MTHFR C677T mutations, protein C, S and AT-III deficiencies did not increase the risk of CAD in our young population.     

静脉血栓患者和正常人凝血因子V Leiden和凝血酶原基因G2021 …

目的 了解静脉血栓虱和正常人中凝血因子Ｖ Ｌｅｉｄｅｎ和凝血酶原基因Ｇ２０２１０Ａ变异的发生率。方法 用多聚酶链反应（ＰＣＲ）及限制性内切酶分析一步法,对９７例静脉血栓患者和１００名正常人的凝血因子Ｖ Ｌｅｉｄｅｎ９ＦＶ Ａｒｇ５０６Ｇｌｎ）和凝血酶原基因Ｇ２０２１０Ａ变异进行分析。结果 凝血因子Ｖ Ｌｅｉｄｅｎ基因和凝血酶原基因ＰＣＲ产物经ＴａｑⅠ酶切消化后电泳显示为１５７ｂｐ和９８ｂｐ片段,静     

静脉血栓患者和正常人凝血因子V Leiden和凝血酶原基因G20210A变异的研究

目的　了解静脉血栓患者和正常人中凝血因子VLeiden和凝血酶原基因G2 0 2 10A变异的发生率。方法　用多聚酶链反应 (PCR)及限制性内切酶分析一步法 ,对 97例静脉血栓患者和 10 0名正常人的凝血因子VLeiden(FVArg5 0 6Gln)和凝血酶原基因G2 0 2 10A变异进行分析。结果　凝血因子VLeiden基因和凝血酶原基因PCR产物( 175bp和 118bp)经TaqI酶切消化后电泳显示分别为15 7bp和 98bp片段 ,静脉血栓患者和正常人群均未发现凝血因子VLeiden和凝血酶原基因G2 0 2 10A变异。结论　我国正常人群和静脉血栓患者凝血因子VLeiden和凝血酶原基因G2 0 2 10A变异发生率低 ,可能不是人群易栓症的主要遗传性危险因素。