血管性血友病因子抗原检测在血友病A与血管性血友病鉴别诊断中的应用

目的评估血管性血友病因子(vWF)抗原检测在血友病(vWD)患者和轻中度血友病A患者鉴别诊断中的价值。方法从2010年8月到2015年12月在我中心检测凝血因子Ⅷ活性低于45%,而且根据临床表现及家族史怀疑为血管性血友病的患者77例,用酶联免疫法和免疫比浊法检测vWF抗原。结果检测的77例患者中29例患者VWF抗原水平低于35%,为vWD患者;48例未检出vWF抗原水平降低。其中女性患者16例中11例vWF抗原水平降低(68.75%),诊断为血管性血友病患者的几率要高于男性患者(29.51%),差异有统计学意义(P0.01)结论凝血因子Ⅷ活性低的患者,特别是女性患者,需要检测vWF抗原水平,筛查是否为vWD。vWF抗原水平检测能很好的满足临床需求,为vWD诊断提供依据,会得到越来越广泛的应用。     

血管性血友病和血管性血友病因子的研究及临床诊治的进展

血管性血友病(vWD)是最常见的遗传性出血性疾病,其发病机制是由于血浆中血管性血友病因子(vWF)的缺乏或结构与功能的异常所致.随着对vWF结构与功能的了解及基因的定位,克隆,基因缺陷的检出,人们已对该病的发生、诊断、治疗都有了更为全面的认识[1].本文就vWD和vWF的研究及临床诊治的进展做一综述.     

血管性血友病和血管性血友病因子的研究及临床诊治的进展

血管性血友病(vWD)是最常见的遗传性出血性疾病,其发病机制是由于血浆中血管性血友病因子(vWF)的缺乏或结构与功能的异常所致.随着对vWF结构与功能的了解及基因的定位,克隆,基因缺陷的检出,人们已对该病的发生,诊断,治疗都有了更为全面的认识[1].本文就vWD和vWF的研究及临床诊治的进展做一综述.     

血管性血友病和血管性血友病因子的研究及临床诊治的进展

血管性血友病(vWD)是最常见的遗传性出血性疾病,其发病机制是由于血浆中血管性血友病因子(vWF)的缺乏或结构与功能的异常所致.随着对vWF结构与功能的了解及基因的定位,克隆,基因缺陷的检出,人们已对该病的发生,诊断,治疗都有了更为全面的认识[1].本文就vWD和vWF的研究及临床诊治的进展做一综述.     

宫内早孕合并血管性血友病行钳刮术1例报告

血管性血友病(von willebrand disease，vWD)是由于血管性血友病因子(vWF)缺乏或异常所引起的一类遗传性出血性疾病。多数患者为常染色体显性遗传，少数为常染色体隐性遗传，临床表现为出血倾向、出血时间延长。vWD是最常见的遗传性出血性疾病，月经过多妇女中可能有20％伴有此病。当vWD患者发生妊娠并要求行人工流产术时，必然增加临床处理的复杂性。现将我院收治的1例宫内早孕合并vWD行钳刮术的病例报告如下。     

ADAMTS13与TSP1在老年急性脑梗死中的意义

目的 探讨血管性血友病因子裂解蛋白酶(ADAMTS13)、凝血酶敏感蛋白1(TSP1)及C1423T基因多态性在老年急性脑梗死患者中的意义。方法 选取62例老年急性脑梗塞患者和56例与之匹配的健康对照者,用vWF：Ag和TSP1 ELISA试剂盒对两组血浆中的vWF：Ag和TSP1含量进行检测,同时残余胶原结合实验(R-CBA)检测两组血浆中的ADAMTS13活性水平,聚合酶链反应(PCR)扩增并限制性酶切扩增产物测定ADAMTS13基因C1423T多态性。结果 急性脑梗死患者血浆中vWF：Ag和TSP1含量均高于正常组(P＜0.05),ADAMTS13活性水平低于正常组(P＜0.05);62例急性脑梗死患者中3例出现C1423T基因突变(4.84%),高于正常组(0%)。结论 ADAMTS13活性降低可能参与脑梗死的发生发展,血浆中的TSP1水平在一定程度上可能促进ADAMTS13对血管性血友病因子(vWF)的裂解;中国汉族人群中基因C1423T突变可能降低ADAMTS13的活性水平,从而参与脑梗死的发生。     

1例并发Ⅰ型血管性血友病的华氏巨球蛋白血症病例报道

患者,男,59岁,因"反复皮肤黏膜出血3年余"就诊.患者曾有外力导致鼻腔出血难以自行止血病史.行凝血相关检查,初步诊断为Ⅰ型血管性血友病(von Willebrand disease,vWD).进一步完善实验室及相关检查,患者免疫球蛋白M(immunoglobulin M,IgM)增高明显,确诊为华氏巨球蛋白血症;同时...     

血管性血友病因子在心脑血管疾病中的表现

目的 探讨血管性血友病因子(von Willebrand factor,vWF)对心脑血管病及偏头痛的影响。方法 以脑出血、脑梗死、冠心病、高血压、心肌梗死、偏头痛患者分别作为病例组，正常体检者和无血管性疾病的患者作为对照组，进行vWF水平测定。结果 病例各组患者vWF水平均高于对照组。结论 表明上述疾病有共同的发病基础，可能与内皮细胞的功能状态有关，vWF可作为一个标志物，为选择治疗药物、判断疗效和预后提供依据。     

血管性血友病因子在偏头痛及脑血管病中的变化

目的　探讨血管性血友病因子 (vonWillebrandfactor,vWF)对偏头痛、脑血管病的影响。方法　以偏头痛、脑梗死、脑出血患者分别作为病例组 ,正常体检者和无血管性疾病的患者作为对照组 ,给予vWF水平测定。结果　偏头痛、脑梗死、脑出血患者vWF水平均高于对照组 (P <0 .0 5 )。结论　这些疾病有共同的发病基础 ,可能与内皮细胞的功能状态有关 ,vWF可作为一个标志物 ,为选择治疗药物、判断疗效和预后提供依据。     

血管性血友病及其相关基因研究

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,发病率(5～10)/10万人口,最高达1％,是由于血浆中vWF因子质或量异常的疾病。vWF在初期止血过程中起着重要的作用。vWF既是血小板膜糖蛋白Gplb/Ⅸ复合物的受体,介导血小板粘附于受损的血管内皮组织,又是血浆中FVⅢ的载体,起着稳定FVⅢ,延长其半衰期的作用。vWD是一组高度异质性的遗传性疾病。利用我国人口众多,vWD的病人来源丰富的优势,提出适合我国的vWD患者正确的诊断和分型的方法,具有重要的临床意义。用分子生物学的手段对中国vWD患者进行分子生物学的研究,     

Von Willebrand disease in China

Purpose To review the molecular pathogenesis in Chinese patients with von Willebrand disease (vWD) and polymorphisms of von Willebrand factor (vWF) in Chinese population. Data sources Both Chinese and English language literature search using MEDLINE (1985-1998), and original articles published in main Chinese and international journals.Study selection and data extraction After reviewing of the literature, 19 articles of them were selected that specifically addressed the stated purpose. Results The molecular pathogenesis of vWD was variant. Six cases of point mutation have been found in Chinese patients with vWD. The system of site-directed mutagenesis and expression of vWF gene was constructed. The polymorphisms of vWF gene are very different between Chinese and Gaucasians. Conclusion Combining to gene mutant in vWD patients, the use of site- directed mutagenesis and expression of vWF will help to understand the vWF function. The polymorphisms of vWF gene are useful marker in Chinese for carrier detection and prenatal diagnosis of vWD.     

Significance of plasma von Willebrand factor level and von Willebrand factor-cleaving protease activity in patients with chronic renal diseases

Background von Willebrand factor （vWF） mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arterial stenosis. On release from endothelial cells, vWF is rapidly cleaved by ADAMTS13/vWF-cleaving protease （vWF-CP）. We investigated the clinical significance of changes in plasma vWF and vWF-CP activities in chronic renal disease.
Methods Plasma vWF and vWF-CP activities were measured using enzyme-linked immunosorbent assay （ELISA） and residual collagen binding assay respectively in patients with lupus nephritis （n=31）, primary nephritic syndrome （n=25）, diabetic nephropathy （n=45）, chronic glomerulonephritis （n=38） and 40 normal controls. The relation of their levels with pathological and renal status was analyzed.
Results In all diseased patients the levels of vWF were significantly higher and vWF-CP activity significantly lower than the controls （both P〈0.01）. vWF in the four subgroups did not correlate with the stage of disease but correlated negatively with vWF-CP activity, vWF-CP activity was not changed two weeks after renal transplantation. Renal biopsy demonstrated that the vWF level in stage IV was higher than in stages II and III while vWF-CP activity was lower in patients with lupus nephritis. After eight-week treatment, the vWF level significantly decreased and the vWF-CP activity significantly increased in systemic lupus erythema, disease activity index 〈9, but not with index 〉9. Even though the vWF-CP activity was significantly lower in membranous nephropathy than in minimal change disease, mesangial proliferative glomerulonephritis or IgA glomerulonephritis, the vWF level was not significantly different.
Conclusions The alterations of plasma vWF and vWF-CP activities were associated with different renal pathologies. Injury to endothelial cells and autoantibodies against vWF-CP activity may result in higher vWF level and lower vWF-CP activity in chronic renal disease an     

von Willebrand disease in China

Ｐｕｒｐｏｓｅ　ＴｏｒｅｖｉｅｗｔｈｅｍｏｌｅｃｕｌａｒｐａｔｈｏｇｅｎｅｓｉｓｉｎＣｈｉｎｅｓｅｐａｔｉｅｎｔｓｗｉｔｈｖｏｎＷｉｌｌｅｂｒａｎｄｄｉｓｅａｓｅ (ｖＷＤ)ａｎｄｐｏｌｙｍｏｒｐｈｉｓｍｓｏｆｖｏｎＷｉｌｌｅｂｒａｎｄｆａｃｔｏｒ (ｖＷＦ)ｉｎＣｈｉｎｅｓｅｐｏｐｕｌａｔｉｏｎ Ｄａｔａｓｏｕｒｃｅｓ　ＢｏｔｈＣｈｉｎｅｓｅａｎｄＥｎｇｌｉｓｈｌａｎｇｕａｇｅｌｉｔｅｒａｔｕｒｅｓｅａｒｃｈｕｓｉｎｇＭＥＤＬＩＮＥ (1985- 1998) ,ａｎｄｏｒｉｇｉｎａｌａｒｔｉｃｌｅｓｐｕｂｌｉｓｈｅ…     

von Willebrand Disease : A Clinico-haematological Spectrum

Background

Bleeding disorders are commonly seen in clinical practice. von Willebrand Disease (vWD), is the commonest and yet a profoundly under diagnosed cause, having a wide spectrum of clinical presentation. Of its three types, type 1 vWD (70% of the total vWD cases) has the mildest and a highly variable clinical and laboratory presentation.

Methods

A series of ten cases of vWD were comprehensively evaluated using recommended diagnostic parameters and therapeutic interventions.

Results

All major types of vWD were represented. A female preponderance, with primary presentation in the form of muco-cutaneous bleeds was observed. A positive history of consanguineous parental marriage and family history of bleeding disorder was elicited in two and three patients respectively. Nine patients were found to be anemic and thrombocytopenia was present in only one. Bleeding time by modified template (SIMPLATE) method, along with activated partial thromboplastin time (APTT) was increased in all ten cases and of these, nine had low factor VIII: C levels. Ristocetin induced platelet aggregation studies were abnormal in all the five cases it was performed. vWF:RCo activity determined in one individual was shown to be low. vWF:Ag assay was done in four cases revealing a near complete absence of von Willebrand factor antigen in one and mildly decreased levels in the other three. vWF multimer assay was advised in three cases. DDAVP, plasma derived vWF, blood products and local antifibrinolytics were used as primary modalities of treatment

Conclusion

Thus, strong clinical suspicion, thorough clinical evaluation and judicious use of investigations including repeated investigations at different times are needed for making a diagnosis of vWD.Key Words: Bleeding disorders, von Willebrand Disease     

妊娠高血压综合征患者血浆von Willebrand因子与一氧化氮水平的变化

目的 :探讨妊娠高血压综合征 (妊高征 )患者血浆vonWillebrand因子 (vWF)和一氧化氮 (NO)水平的变化。方法 :分别采用酶联免疫吸附试验 (ELISA法 )和Griess法测定 36例妊高征患者及 18例正常妊娠妇女血浆vWF和NO水平。结果 :中、重度妊高征患者血浆vWF高于正常妊娠妇女 ;妊高征患者血浆NO水平低于正常妊娠妇女 ;vWF水平越高或NO水平越低 ,妊高征病情越重。中、重度妊高征患者血浆vWF与NO呈明显负相关 (r =- 0 .5 48,P<0 .0 1)。结论 :vWF和NO可作为判断妊高征病情程度的指标 ;vWF和NO在中重度妊高征患者的发病中起相互拮抗作用     

乌司他汀对兔脑出血脑保护作用的实验研究

目的:通过观察脑出血兔血清可溶性血栓调节蛋白(STM)、血管假血友病因子(vWF)、一 氧化氮(NO)含量变化,探讨乌司他汀的脑保护作用.方法:40只新西兰大白兔随机分为正常对照 组、模型组、乌司他汀 1天组和乌司他汀 3天组,每组 10只.用自体血法制备兔脑出血模型,应用 Ellisa法测定各组兔血清STM、vWF、NO含量.结果:与正常对照组比较,模型组STM、vWF和NO含 量显著增高(P<0.05).乌司他汀 1天组、3天组的STM、vWF和NO均低于模型组(P<0.05),乌司他 汀 3天组STM、vWF和NO含量与乌司他汀 1天组比较,差异无统计学意义(P>0.05).结论:乌司他 汀抑制STM、vWF和NO生成,从而减轻脑出血兔脑细胞的损伤,具有脑保护作用.     

血液病患者出血程度与PMP、vWF、FN的关系及临床意义

目的 观察血小板微颗粒(PMP)、血管性血友病因子(vWF)、纤维连接蛋白(FN)在血小板减少的血液病患者中与出血程度的关系,探讨PMP、vWF、FN对出血程度预测的临床意义.方法 根据WHO关于出血的分级标准,将患者分为0分组、1分组、2分组、3分组、4分组及对照组.应用流式细胞术检测患者外周血中PMP含量变化,应用ELISA法检测患者外周血中vWF、FN含量变化.结果 ① 各组PMP、vWF、FN的含量差异均有统计学意义(P<0.001);② 不同出血程度组之间出血程度越重,PMP含量越低[除1分组与2分组;3分组、4分组和对照组差异无统计学意义,其余差异有统计学意义(P<0.001)]、VWF含量越高[除1分组与2分组外,其余各组之间差异有统计学意义(P<0.001)]、FN含量越高[除0分组与1分组外,其余各组均差异有统计学意义(P<0.001)].结论 PMP、vWF、FN的含量对血小板减少的血液病患者出血程度的预测具有临床意义.     

维持性血液透析患者血浆P-选择素及von Willebrand因子的变化

目的　研究尿毒症维持性血液透析 (MHD)患者血浆P 选择素及vonWillebrand因子 (vWF)的变化 ,并探讨其临床意义。方法　应用双抗体夹心酶联免疫吸附 (ELISA)法测定 68例MHD患者 (MHD组 )和 2 0例健康对照者 (对照组 )P 选择素、vWF含量 ,同时作颈动脉超声检测患者动脉粥样硬化情况。结果　 ( 1)MHD组P 选择素、vWF水平显著高于对照组(均P <0 0 1) ,MHD组中有颈动脉粥样硬化者P 选择素、vWF水平显著高于无颈动脉粥样硬化者 (P <0 0 5 ,P <0 0 1)。( 2 )MHD组vWF含量与甘油三酯水平呈正相关 (r=0 45 31,P <0 0 5 )。结论　MHD患者存在明显的血管内皮功能损害和血小板活化 ;P 选择素、vWF参与了MHD患者动脉粥样硬化的发生、发展过程 ;P 选择素、vWF可作为反映MHD患者内皮功能损害和血小板活化的生化标志物     

Evaluation of von Willebrand factor-cleaving protease activity in patients with thrombotic thrombocytopenic purpura

Background Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. In this study we investigated the von Willebrand factor-cleaving protease (vWF-cp) activity deficiency in patients with TTP.Methods The plasma or serum vWF-cp activity was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) by detecting the residual collagen binding activity (R-CBA) of von Willebrand factor (vWF) before and after digestion by vWF-cp. Multimers of vWF in plasma of patients with TTP were also analyzed by SDS-agarose electrophoresis. Moreover, the serum vWF-cp activities were compared between the patients with TTP and those with tumors.Results The coefficient of variation for intra-batch and inter-batch of the assay were 3.60％ and 8.35％. The plasma and serum vWF-cp activity in healthy individuals were (78.79±9.17)% (n=30) and (79.47±10.78)% (n=53), respectively, while the plasma vWF-cp activity in 5 patients with TTP was markedly decreased ［(21.83±19.98)%, P&lt;0.001］. The unusually large vWF multimers were observed in two plasma samples of the patients with TTP. Although the vWF-cp activities in patients with benign and malignant tumors were also decreased (P&lt;0.03 and P&lt;0.001, respectively), they were relatively high in comparison with that of TTP patients (P&lt;0.001).Conclusion Measurement of the vWF-cp activity using R-CBA is a simple and rapid method for diagnosing TTP. The vWF-cp activity in patients with TTP was markedly lower than those of patients with tumors.