Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications
Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications
复制标题
DOI：
10.3324/haematol.2008.003301
复制
发表时间：
2009-05-01
期刊：
影响因子：
--
通讯作者：
Batlle, Javier
中科院分区：
文献类型：
--
作者：
Perez-Rodriguez, Almudena;Garcia-Rivero, Aranzazu;Batlle, Javier
研究背景血管性血友病因子（vonWillebrandfactor，VWF）基因C1149 R突变被认为是导致常染色体显性遗传的严重1型血管性血友病（vonWillebranddisease，VWD）的原因。VWF胶原结合（VWF：CB）和降低瑞斯托霉素诱导的血小板聚集（RIPA）。VWF：RCo/VWF：Ag和VWF：CB/VWF：Ag比率低于0.7。在基础条件下，血浆中所有VWF多聚体均减少，高分子量VWF多聚体（HMWM）的相对比例明显降低。在高分辨率琼脂糖凝胶中，卫星带的相对比例大幅下降。患者对去氨加压素（DDAVP）给药有短暂的良好反应，但释放的VWF半衰期短于正常。表明他们的VWF清除加速了血小板VWF是abnormal.ConclusionsWe得出结论，从这些患者的血浆表型数据，这种突变应被归类为VWD 2A型（IIE）的结果。DDAVP治疗可能对这种突变有一定帮助，至少对轻度至中度出血有帮助。这些数据提供的证据表明，对于VWD分类，应考虑基础VWF以外的因素，如DDAVP反应和血小板VWF。
BackgroundMutation C1149R in the von Willebrand factor (VWF) gene has been thought to cause autosomal dominant severe type 1 von Willebrand disease (VWD).Design and MethodsEight patients from three unrelated families with this mutation were included in the present study who had distinct VWF abnormalities; not described in earlier studies.ResultsThe patients showed notably low levels of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo); VWF collagen binding (VWF:CB), and a reduced ristocetin-induced platelet aggregation (RIPA). VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios were lower than 0.7. At basal conditions, all the VWF multimers were decreased in plasma, with a clearly lower relative proportion of the high molecular weight VWF multimers (HMWM). In high-resolution agarose gels, a large decrease in the relative proportions of the satellite bands was seen. The patients had a brief good response to desmopressin (DDAVP) administration, but the released VWF half-life was shorter than normal,. indicating an accelerated clearance of their VWF. Platelet VWF was abnormal.ConclusionsWe conclude from the results obtained in these patients for plasma phenotypic data that this mutation should be classified as a VWD type 2A (IIE). DDAVP therapy may be somewhat helpful for this mutation, at least for mild to moderate bleeding. These data provide evidence that for VWD classification factors other than basal VWF, such as DDAVP response and platelet VWF, should be considered.