Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD (MCMDM-1VWD)
Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD (MCMDM-1VWD)
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DOI：
10.1182/blood-2007-09-110940
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发表时间：
2008-05-15
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.;Castarnan, Giancarlo;Montgomery, Robert R.
血浆中血管性血友病因子（VWF）的存活率降低已被认为是1型血管性血友病（VWD）患者亚组的一种机制。我们以前曾报道，VWF及其前肽（VWFpp）的血浆水平的比例可以用来确定VWF生存减少的患者。在这项研究中，我们报告了MCMDM-1VWD研究中从6个欧洲中心招募的19名个体的VWFpp和VWF：Ag测定。8名患者的VWF：Ag水平低于30 IU/dL。这些患者中有7例具有强有力的去氨加压素反应，并且通过显著增加的稳态血浆VWFpp/VWF：Ag比率预测VWF半衰期显著缩短。在7个个体中的每一个中鉴定了先前与VWF存活率降低相关的VWF突变。因此，稳态VWFpp/ VWF：Ag比值的显著增加预示着VWF：Ag水平显著降低的患者的VWF半衰期缩短。这些数据表明，在1型VWD患者亚群中发现VWF存活率降低。在中重度1型VWD患者中，血浆VWF和VWF前肽的系统测定可鉴定具有降低的VWF存活表型的患者。
The decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. We have previously reported that the ratio of plasma levels of VWF and its propeptide (VWFpp) can be used to identify patients with reduced VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half-life that was predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF mutations previously associated with reduced VWF survival were identified in each of the 7 individuals. Thus, a substantially increased ratio of steady-state VWFpp/ VWF:Ag predicted a reduced VWF half-life in patients with markedly decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found in a sub-population of patients with type 1 VWD. The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype.