急性冠脉综合征与血管性血友病因子裂解酶的关系

目的 观察急性冠脉综合征(ACS)患者血浆血管性血友病因子裂解酶(vWF-cp)水平变化及临床意义.方法 ACS分不稳定型心绞痛(UAP)组和急性心肌梗死(AMI)组,其中UAP 17例,AMI 17例,分别于急性期(入院后即刻)和恢复期(4周)采血;稳定型心绞痛(SAP)组17例和健康对照组17例,入院次日空腹采血.所有入选对象均行冠状动脉造影证实.应用残余胶原结合力试验测定血浆vWF-cp活性水平.结果 ①UAP组[(53.17±11.72)%]和AMI组[(46.47±11.81)%]急性期血浆vWF-cp活性水平均低于SAP组[(77.00±10.42)%],(P＜0.01)和正常对照组[(80.79±17.25)%],(P＜0.01),而UAP组和AMI组之间比较、SAP组和正常对照组之间比较差异无统计学意义(P均＞0.05).②UAP组(53.17±11.72)%]和AMI组[(46.47±11.81)%]vWF-cp活性水平急性期低于恢复期[UAP组(79.58±7.588)%;AMI组(81.41±6.851)%],(P＜0.01).结论 血浆vWF-cp活性降低在ACS血栓形成中可能起重要作用.     

血浆hs—CRP、vWF及其裂解酶含量与急性冠脉综合征

目的：检测不稳定型心绞痛（UAP）、急性心肌梗死（AMI）等急性冠脉综合征（ACS）患者血浆中高敏C反应蛋白（h—CRP）和血管性血友病因子（vWF）及其裂解酶（vWF-cp）水平，探讨它们在ACS发病机制中的作用和相互联系。方法：研究对象分UAP组和AMI组（入院即刻采血），稳定型心绞痛（SAP）组和正常对照组（于入院次日空腹采血），各组均17例；应用酶联免疫吸附试验（ELISA）测定血浆vWF浓度和hs-CRP含量，以残余胶原结合力试验测定血浆vWF-cp活性水平。所有入选对象均行冠状动脉造影证实。结果：①UAP组和AMI组血浆hs-CRP与vWF水平均高于SAP组和正常对照组（P〈0．01）；②UAP组和AMI组血浆vWF—cp活性水平均低于SAP组和正常对照组（P〈0．01）；③ACS患者血浆hs—CRP与vWF水平间呈显著正相关（r=0．67，P〈0．01），而血浆vWF-cp与vWF、hs—CRP无明显相关关系。结论：①血浆hs—CRP、vWF水平升高可能是预测ACS斑块破裂和血栓形成的指标；②血浆vWF—cp活性降低在ACS血栓形成中可能起重要作用。     

急性冠脉综合征患者炎症标志物水平及其临床意义

目的探讨炎症标志物与急性冠脉综合征（ACS）的关系及临床意义。方法ELISA测定22例急性心肌梗死（AM I）、37例不稳定型心绞痛（UAP）患者及对照组30例外周血可溶性血管间内皮细胞黏附分子（vascu lar celladhesion molecu le-1,sVCAM-1）和血管性假性血友病因子（von W illebrand Factor,vWF）浓度,所有患者均行冠状动脉造影,记录血管病变情况。结果血清sVCAM-1浓度在AM I组明显高于UAP组及对照组（P<0.01）,UAP组明显高于对照组（P<0.01）;血浆vWF浓度在AM I组与UAP组均显著高于对照组（P<0.01）,但AM I组与UAP组比较无统计学意义;血清sVCAM-1与受累冠状动脉血管支数成正相关,r=0.450,P<0.01。而vWF水平与受累冠状动脉血管支数无相关关系,r=0.074。结论血清sVCAM-1与冠状动脉病变程度密切相关,vWF与ACS的发生发展相关联。     

NECA对兔急性心肌缺血再灌注后vWF水平的影响

目的建立兔急性缺血再灌注模型，观察腺苷受体激动剂NECA（5＇-N-ethylcarbo-xamidoad-enosine）对兔急性心肌缺血再灌注后血管性假血友病因子（von Willebrand factor vWF）水平的影响，探讨其对兔急性缺血再灌注心肌的保护作用。方法新西兰大耳白兔24只，随机分成三组，对照组（n=8）、后处理组（n=8）、NECA后处理组（n=8），均建立急性缺血再灌注模型。用RT-PcR方法测定vWF的mRNA表达，酶联免疫吸附双抗体夹心法（ELISA）测定AMI前5min、再灌注前5min、再灌注后60min血浆vWF的水平。结果与对照组相比，NECA组心肌组织vWF的mRNA的表达和再灌注后60min血浆vWF水平降低（P〈0．05），NECA组与后处理无显著差别（P〉0，05）。结论NECA能够降低兔急性缺血再灌注后vWF的水平，其对冠状动脉血管内皮细胞具有保护作用。     

不同程度冠状动脉病变患者的血管性假血友病因子检测

目的探讨不同程度冠脉病变患者的血管性假血友病因子（von Willebrand factor,vwF）水平。方法检测111例冠心病（CHD）及25例非CHD患者的血浆vWF水平。对所有人选患者行冠脉造影检查,将CHD患者根据冠状动脉病变支数分为单支、双支和多支病变组;根据冠状动脉损伤形态分为A型低危病变组、B型中危病变组和C型高危病变组;分析血浆vWF水平与冠状动脉病变的范围及程度的关系。结果CHD多支病变组的血浆vWF水平较单支病变组、双支病变组明显升高[（197．42±6．57）％比（135．24±21．56）％、（170．94±15．75）％,P〈0．01、P〈0．05];双支病变组的血浆vWF水平较单支病变组也明显升高（P〈0．05）;对照组与单支病变组的血浆vWF水平差异无统计学意义。C型病变组vwF高于A型、B型病变组[（195．25±33．71）％比（132．10±28．26）％、（161．13±37．41）％,19〈0．01],B型病变组高于A型病变组（P〈0．01）。结论血浆vwF水平能反映冠脉病变的范围及程度。     

血管性血友病和血管性血友病因子的研究进展

血管性血友病（von Willebrand disease，vWD）是最常见的遗传性出血性疾病之一。根据多中心研究的结果估计，有症状的vWD患者达113／10^6或更高，而具有vWD危险的人数高达1480／10^6～3580／10^6。1926年芬兰医师von Willebrand首次发现该病，并认识到其是常染色体的遗传性出血性疾病。通过对vWD的病理机制的研究，已明确该病是由于血浆中一种多聚糖蛋白，即血管性血友病因子（vWF）缺陷所致，且这种缺陷是由于vWF基因突变所导致。     

脑梗死患者血浆EDRF、vWF、TNF含量变化探讨

目的观察脑梗死患者内皮细胞舒张因子(EDRF),血管性假血友病因子(vWF)及肿瘤坏死因子(TNF)血浆中的含量。方法测定42例急性期脑梗死患者,38例恢复期脑梗死患者及40例正常人血浆E-DRFv、WF、TNF含量,并分析其相互关系。结果(1)急性期脑梗死患者vWF、TNF较对照组明显升高(P<0.01),EDRF明显降低(P<0.01)。(2)大梗死组与小梗死组相比较,vWF、TNF水平升高和EDRF水平下降均有显著差异(P<0.01)。(3)急性期脑梗死患者vWF升高与TNF呈正相关(r=0.72、P<0.01),vWF升高与E-DRF呈负相关(r=-0.74,P<0.01)。(4)恢复期脑梗死患者vWF、TNF及EDRF与对照组比较,无显著差异(P>0.05)。结论急性脑梗死患者存在内皮细胞损伤和功能障碍。     

血浆血管性血友病因子水平与冠状动脉病变的关系

目的:测定血浆血管性血友病因子(vWF)浓度,探讨血浆vWF水平与冠状动脉病变之间的关系。方法:根据冠状动脉造影结果选择冠心病患者78例,分为单支病变组、双支病变组、多支病变组,测定其血浆vWF水平,并与冠状动脉病变积分作相关分析。同时选非冠心病患者29例作为正常对照组。结果:冠心病组血浆vWF水平较正常对照组血浆vWF水平明显升高,(181.24±26.56)%∶(157.11±26.63)%,P<0.01;多支病变组较单支病变组、双支病变组的血浆vWF水平明显升高,(195.52±26.57)%∶(165.24±26.90)%、(180.54±18.58)%,P分别<0.01、<0.05;双支病变组较单支病变组的血浆vWF水平也明显升高(P<0.05),对照组与单支病变组的血浆vWF水平无差异。血浆vWF水平与冠状动脉病变积分呈正相关(r=0.702,P<0.01)。结论:血浆vWF水平可较好反映冠心病患者血管内皮功能损伤程度和冠状动脉病变范围。     

缬沙坦对伴有高血压病的代谢综合征患者血管性假血友病因子的影响

目的 观察伴有高血压病的代谢综合征（metabolic syndrome,MS）患者血浆血管性假血友病因子（von Willebrand factor,vWF）水平及应用缬沙坦后vWF的变化。方法 测定22例伴有高血压病的MS患者服用缬沙坦80 mg/d4周前后及29例健康体检者血浆vWF含量。结果 伴高血压病的MS患者血浆vWF显著高于健康对照者［(176±24)% vs (130±26)%,P<0.01］;vWF含量与收缩压（SBP）［r＝0.60,P<0.01］、舒张压（DBP）［r＝0.57,P<0.01］、平均动脉压（MAP）［r＝0.61,P<0.01］、体质量指数（BMI）［r＝0.53,P<0.01］、三酰甘油（TG）［r=0.36,P<0.05］、总胆固醇（TC）［r=0.49,P<0.01］、空腹血糖（FBG）［r＝0.45,P<0.01］呈正相关;缬沙坦治疗4周后,伴高血压病的MS患者血浆vWF水平较治疗前显著降低［(160±15)% vs (176±24)%,P<0.01］。结论 伴高血压病的MS患者血浆vWF水平较健康人明显增高;予缬沙坦治疗后,在有效降低血压的同时,可短期内降低vWF水平,改善血管内皮功能。     

依诺肝素和那屈肝素治疗非ST段抬高的急性冠状动脉综合征

目的比较依诺肝素（enoxaparin）与那屈肝素（nadroparin）对非sT段抬高的急性冠状动脉综合征患者临床预后的影响以及患者血浆中的血管性血友病因子（von Willebrand factor，vwF）、高敏C反应蛋白（high sensitivity C reactiveprotein，hs-CRP）水平。方法非ST段抬高的急性冠状动脉综合征患者70例，随机分人依诺肝素组与那屈肝素组，比较两组30d内的终点事件和出血事件的发生率。两组均检测入选时，用药后4，12及66h血浆vWF、hs—CRP水平。结果①30d临床事件：那屈肝素组为10，依诺肝素组为12，差异无统计学差意义（P〉0．05）；②两组均未发生严重出血事件，微小出血事件：那屈肝素组4例，依诺肝素组2例；③两组各时间点对应的vWF、hs—CRP水平差异无统计学意义（P〉0．05）。结论对于NSTE—ACS患者的治疗，两种低分子量肝素治疗非ST段抬高的急性冠状动脉综合征效果及对炎性因子作用基本一致。     

血管性血友病因子及其裂解酶与系统性红斑狼疮的关系

目的检测系统性红斑狼疮(SLE)患者血浆血管性血友病因子(VWF)水平及VWF裂解酶(VWF-CP)活性,探讨VWF及VWF-CP在SLE中的临床意义。方法采用残余胶原结合实验法及ELISA法分别对30例SLE患者血浆VWF-CP活性及VWF:AG水平进行检测。结果SLE患者血浆VWF:AG(114.6±16.3)%显著高于正常对照组(71.3±49.5)%(P<0.01),而血浆VWF-CP活性水平(57.7±16.3)%显著低于正常对照组(86.6±1.8)%(P<0.01),狼疮性肾炎(LN)组(130.1±40.6)%血浆VWF:AG水平显著高于非LN组(97.6±27.6)%(P<0.05),而VWF-CP活性显著降低(P<0.05),血浆VWF-CP活性水平与狼疮活动指数(SLEDAI)呈负相关(R=-0.4316,P<0.05)。18例肾活检的LN患者中,Ⅳ型VWF水平最高,VWF-CP活性最低,其余3型之间无差别。30例初发SLE患者综合治疗4周后血浆VWF:AG水平显著下降,VWF-CP活性水平在治疗后SLEDAI评分≥9分者,无显著性升高,SLEDAI评分<9分者,有显著性升高(P<0.05)。结论SLE的血浆VWF升高,VWF-CP活性低下,参与SLE尤其是LN的发生发展,内皮损伤和自身抗体可能是致SLE患者VWF升高,VWF-CP活性低下的原因。     

血浆血管性血友病因子裂解酶在肝脏疾病发病机制和诊断中的作用

近期研究表明机体凝血功能和肝脏微循环障碍在肝脏疾病的发生、发展过程中起着重要作用。ADAMTS13又称血管性血友病因子裂解酶,是由肝星状细胞产生的金属蛋白酶,主要功能是裂解血管内皮细胞产生的血管性血友病因子多聚体,从而调节血小板粘附能力,进而影响机体的凝血功能和微循环。回顾ADAMTS13在多种重症肝病如肝硬化、重症酒精性肝炎、干细胞移植后肝静脉阻塞病和移植肝功能障碍等病理生理过程中发挥的重要作用,阐述了其与肝脏疾病严重程度的关系,认为血浆ADAMTS13参与了多种肝脏疾病的发生、发展过程,通过检测其水平和活性有助于肝脏疾病的诊断及鉴别诊断。     

Optimizing therapy with factor VIII/von Willebrand factor concentrates in von Willebrand disease

In von Willebrand disease, the main goals of treatment are to correct the dual defect of haemostasis caused by a reduced or abnormal von Willebrand factor (vWF), i.e. the prolonged bleeding time (BT) and the deficiency of factor VIII coagulant activity (FVIII:C). The synthetic vasopressin analogue, desmopressin (DDAVP), has reduced the need for transfusions in most of the mild forms of von Willebrand disease but DDAVP is ineffective in type 3 and in other severe cases of types 1 and 2 von Willebrand disease. For many years cryoprecipitate has been the mainstay of replacement therapy but, after the introduction of virucidal methods, concentrates containing FVIII/vWF have been considered much safer than cryoprecipitate and proposed in von Willebrand disease management. FVIII/vWF concentrates have been produced and tested by many authors but there is only one report describing four virus-inactivated FVIII/vWF concentrates evaluated in a cross-over randomized trial. According to these in vitro and pharmacokinetic data, the following information can be derived: (a) no FVIII/vWF concentrate had an intact multimeric structure similar to that of normal plasma or of cryoprecipitate; (b) all FVIII/vWF concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed in the concentrate devoid of FVIII:C; (c) no FVIII/vWF concentrate consistently normalized the BT in a sustained fashion. On the other hand, clinical haemostasis can be achieved in the management of bleeding episodes and of surgery for most of von Willebrand disease cases regardless of whether the BT is corrected; in the few rare cases with mucosal bleeding not controlled by FVIII/vWF concentrates, infusion of DDAVP or platelet concentrates can be administered in addition.     

阿托伐他汀对高血压病血vWF及BNP影响的近期疗效观察

目的探讨不同剂量阿托伐他汀治疗对血管内皮功能及脑钠肽（BNP）水平的影响。方法在我院确诊的150例高血压病同时具有高脂血症患者随机分成A、B、C三组，分别接受10、20、40mg／d阿托伐他汀治疗4周。比较3组血脂水平、血管内皮功能相关指标血管性假性血友病因子（vWF）及BNP水平。结果与治疗前比较，不同剂量阿托伐他汀治疗组vWF及BNP水平均明显下降，C组明显低于A、B组（P〈0．01），3组不良反应相似。结论阿托伐他汀降脂治疗可改善高血压病患者的内皮功能，40mg阿托伐他汀作用比较明显。     

von Willebrand disease type IIC with different abnormalities of von Willebrand factor in the same sibship

A family with von Willebrand disease has been identified in which different members of the same sibship exhibit different abnormalities of von Willebrand factor (vWF). The two most severely affected sibs (bleeding time over 20 min) had abnormalities of vWF similar to those seen in type IIC. The smallest detectable multimer was increased and the triplet structure of individual multimers was replaced with a single band. The largest multimers could not be detected and there were relatively more small multimers than intermediate sized forms. vWF antigen (vWF:Ag) was decreased to 12.5-17% by electroimmunoassay (EIA) and to 3.2-5.5% by immunoradiometric assay (IRMA). In the less severely affected sibling (bleeding time 12.5 min) there was a similar relative increase in the smallest detectable multimer. However, the larger multimers were present and the relative concentration of large to small multimers was similar to normal. The triplet structure was altered in that the relative proportion of satellite bands to the central predominant band was decreased. vWF:Ag concentrations were moderately decreased (40-80% by EIA and 25-35% by IRMA). The father and grandfather showed a vWF multimeric pattern similar to the less severely affected sibling but there was no decrease in vWF:Ag concentration and their bleeding times were normal. These observations suggest that the interplay of several genetic factors is responsible for the expression of von Willebrand disease in this family.     

von Willebrand factor containing factor VIII concentrates

There are several plasma derived von Wille-brand factors (vWF) containing factor (FVIII) concentrates that can be used in the treatment of von Willebrand disease (vWD). All concentrates are effective in attaining normal postinfusion levels or of FVIII:C but it is difficult to achieve normalization of the bleeding time even with concentrates containing almost all vWF multimers including those of high molecular weight. Haemate P (Centeon) may be considered as the golden standard concentrate available at present. However, the development of more purified vWF concentrates devoid of FVIII:C is the goal for future development.     

Prophylaxis in von Willebrand disease

Von Willebrand disease (VWD), the most common hereditary bleeding disorder, is divided into three types depending on the quantitative (type 1 and 3) or qualitative (type 2) abnormality of von Willebrand factor (VWF). About 70–80% of VWD patients can be treated with the synthetic product desmopressin, while the others necessitate factor VIII/VWF concentrates. In addition to the treatment of bleeding episodes, therapeutic regimens include short- or long-term prophylaxis. While the literature data on short-term prophylaxis in VWD are consistent and clearly show the safety and efficacy of such a therapeutic approach, little evidence is available regarding long-term prophylaxis, and although the preliminary results are encouraging, they need to be validated by large prospective studies.     

Diagnosis of von Willebrand disease

Summary. von Willebrand disease (vWD) is a bleeding disorder caused by quantitative or qualitative defects of von Willebrand factor (vWF). vWF is synthesized by endothelial cells and megakaryocytes and circulates in plasma as a multimeric high molecular weight glycoprotein. vWF plays a major role in the early phases of ostasis by promoting platelet-vessel wall and plateletplatelet interactions under high shear conditions. It is also the carrier of coagulation factor VIII (FVIII) in plasma. A deficiency of vWF results in impairment of both primary and secondary phases of ostasis. Therefore, patients with vWD manifest bleeding symptoms that are typical of defects of primary ostasis (mucocutaneous haemorrhages) but, in case of severe deficiency of vWF, there are also haemarthroses and haematomas, which are typical of those seen with coagulation defects. Several types and subtypes of vWD have been described with a high degree of heterogeneity. The diagnosis is based on measurements of plasma and platelet vWF, the ability of vWF to interact with its platelet receptor and the analysis of the multimeric composition of vWF. Due to the heterogeneity of vWF defects, a correct diagnosis of types and subtypes may be sometimes difficult but is very important for an appropriate treatment of patients with vWD.     

The molecular characterization of von Willebrand disease: good in parts

Since the cloning of the gene that encodes von Willebrand factor (VWF), 27 years ago, significant progress has been made in our understanding of the molecular basis of the most common inherited bleeding disorder, von Willebrand disease (VWD). The molecular pathology of this condition represents a range of genetic mechanisms, some of which are now very well characterized, and others that are still under investigation. In general, our knowledge of the molecular basis of type 2 and 3 VWD is now well advanced, and in some instances this information is being used to enhance clinical management. In contrast, our understanding of the molecular pathogenesis of the most common form of VWD, type 1 disease, is still at an early stage, with preliminary evidence that this phenotype involves a complex interplay between environmental factors and the influence of genetic variability both within and outside of the VWF locus.     

Treatment of von Willebrand disease

Summary. von Willebrand disease is the most frequent of inherited bleeding disorders (1:100 affected individuals in the general population). The aim of treatment is to correct the dual defects of haemostasis, i.e., abnormal coagulation expressed by low levels of factor VIII and abnormal platelet adhesion expressed by a prolonged bleeding time. There are two main options available for the management of von Willebrand disease: desmopressin and transfusion therapy with blood products. Desmopressin is the treatment of choice in patients with type 1 von Willebrand disease, who account for approximately 80% of cases. This pharmacological compound raises endogenous factor VIII and von Willebrand factors and thereby corrects the intrinsic coagulation defect and the prolonged bleeding time in most type 1 patients. In type 3 and in the majority of type 2 patients desmopressin is not effective, and it is necessary to resort to plasma concentrates containing factor VIII and von Willebrand factor. Treated with virucidal methods, these concentrates are effective and currently safe, but the bleeding time defect is not always corrected by them. Platelet concentrates or desmopressin can be used as adjunctive treatments when poor correction of the bleeding time after concentrates is associated with continued bleeding.