Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival
Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival
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DOI：
10.1182/blood-2006-04-015065
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发表时间：
2006-11-15
期刊：
影响因子：
20.3
通讯作者：
Montgomery, Robert R.
中科院分区：
文献类型：
--
作者：
Haberichter, Sandra L.;Balistreri, Michael;Montgomery, Robert R.
1 型血管性血友病 (VWD) 的特征是血管性血友病因子 (VWF) 部分数量缺乏。已发现很少有 VWF 基因突变会导致显性 1 型 VWD。血浆中 VWF 存活率的降低最近被确定为 1 型 VWD 的一种新机制。我们报告了 4 个患有中重度 1 型 VWD 的家族，其特征是血浆 VWF:Ag 和 FVIII:C 水平低、VWF:RCo 比例较低以及显性遗传。受影响个体中 VWF 的存活率降低，VWF 半衰期为 1 至 3 小时，而 VWF 前肽 (VWFpp) 的半衰期正常。 DNA 测序显示受影响个体中存在单一（杂合）VWF 突变，2 个家族中有 S2179F，2 个家族中有 W1144G，此前均未报道过这两种突变。我们表明，稳态血浆 VWFpp 与 VWF:Ag 的比率可用于识别 VWF 半衰期缩短的患者。所有家庭中受影响的个体与未受影响的个体的比率有所增加。 VWFpp/VWF:Ag 比率显着增加以及 VWF:Ag 降低可能表明存在真正的遗传缺陷和 VWF 存活表型降低。这种表型可能需要改变临床治疗方法，我们建议将此表型称为 1C 型 VWD。
Type 1 von Willebrand disease (VWD) is characterized by a partial quantitative deficiency of von Willebrand factor (VWF). Few VWF gene mutations have been identified that cause dominant type 1 VWD. The decreased survival of VWF in plasma has recently been identified as a novel mechanism for type 1 VWD. We report 4 families with moderately severe type 1 VWD characterized by low plasma VWF:Ag and FVIII:C levels, proportionately low VWF:RCo, and dominant inheritance. A decreased survival of VWF in affected individuals was identified with VWF half-lives of 1 to 3 hours, whereas the half-life of VWF propeptide (VWFpp) was normal. DNA sequencing revealed a single (heterozygous) VWF mutation in affected individuals, S2179F in 2 families, and W1144G in 2 families, neither of which has been previously reported. We show that the ratio of steady-state plasma VWFpp to VWF:Ag can be used to identify patients with a shortened VWF half-life. An increased ratio distinguished affected from unaffected individuals in all families. A significantly increased VWFpp/VWF:Ag ratio together with reduced VWF:Ag may indicate the presence of a true genetic defect and decreased VWF survival phenotype. This phenotype may require an altered clinical therapeutic approach, and we propose to refer to this phenotype as type-1C VWD.