Ristocetin dependent cofactor activity in von Willebrand disease diagnosis: Limitations of relying on a single measure.
Ristocetin dependent cofactor activity in von Willebrand disease diagnosis: Limitations of relying on a single measure.
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DOI：
10.1002/rth2.12807
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发表时间：
2022-10
影响因子：
4.6
通讯作者：
Montgomery, Robert R.
中科院分区：
文献类型：
--
作者：
Christopherson, Pamela A.;Haberichter, Sandra L.;Flood, Veronica H.;Sicking, Ursula O.;Abshire, Thomas C.;Montgomery, Robert R.
关键词：
血管性血友病（VWD）是一种常见的遗传性出血性疾病，然而，由于主观出血史和一些目前的血管性血友病因子（VWF）实验室分析的问题，诊断可能会变得复杂。在Zimmerman项目中，我们试图确定1型诊断的频率是基于由常见遗传变异p.D1472H引起的单一低VWF里斯托素辅助因子（VWF:RCo）水平或孤立的分析问题，如果该低值被VWF糖蛋白- IbM （VWF:GPIbM）分析证实，以及如果重新测试证实了原始水平。新患者被同意接受出血评估。分析包括VWF测序、出血评分、局部VWF抗原（VWF:Ag）和VWF:RCo与中央VWF:Ag和VWF:GPIbM的比较。共有18%的VWD受试者局部VWF:RCo较低，但VWF:Ag正常，包括VWF:GPIbM在内的中心测试正常。70%的低VWF:RCo组没有致病性VWF变异；然而，33%携带p.D1472H。低VWF:RCo受试者在2年内随访的局部检测显示，p.D1472H患者的VWF:RCo和VWF:RCo/VWF:Ag比与正常VWF:GPIbM相比，继续保持较低的VWF:RCo和VWF:RCo/VWF:Ag比。没有p.D1472H的受试者的平均VWF:RCo增加，59%的人在重复测试中处于正常水平。VWD的诊断基于单一的低VWF:RCo，但VWF:Ag正常，通常归因于p.D1472H或VWF:RCo的变异性，而VWF:GPIbM可以消除这种变异性。我们的研究表明，仅使用VWF:RCo进行诊断可能是不够的，而重复VWF:RCo或VWF:GPIbM检测对于建立VWD诊断可能是有价值的。
Von Willebrand disease (VWD) is a common inherited bleeding disorder, however the diagnosis can be complicated by a subjective bleeding history and issues with some current von Willebrand factor (VWF) laboratory assays. In the Zimmerman Program, we sought to determine how often a type 1 diagnosis was based on a single low VWF ristocetin cofactor (VWF:RCo) level resulting from the common genetic variant p.D1472H or an isolated assay issue, if that low value was corroborated by the VWF glycoprotein‐IbM (VWF:GPIbM) assay, and if retesting confirmed original levels. New patients being evaluated for bleeding were consented. Analysis included VWF sequencing, bleeding scores, and comparisons of local VWF antigen (VWF:Ag) and VWF:RCo to central VWF:Ag and VWF:GPIbM. A total of 18% of VWD subjects had a low local VWF:RCo, but normal VWF:Ag and normal central testing including VWF:GPIbM. Seventy percent of the low VWF:RCo cohort had no pathogenic VWF variants; however, 33% carried p.D1472H. Low VWF:RCo subjects with follow‐up local testing within 2 years showed those with p.D1472H continued to have low VWF:RCo and VWF:RCo/VWF:Ag ratio with normal VWF:GPIbM. Subjects without p.D1472H had an increase mean VWF:RCo, resulting in 59% with normal levels on repeat testing. The diagnosis of VWD based on a single low VWF:RCo but normal VWF:Ag, was often attributed to p.D1472H or variability in VWF:RCo that was eliminated with VWF:GPIbM. Our study suggests that using VWF:RCo alone for diagnostic purposes may be insufficient while repeat VWF:RCo or VWF:GPIbM testing can be valuable in establishing a VWD diagnosis.
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影响因子：
20.3
作者：
Flood, Veronica H.;Gill, Joan Cox;Montgomery, Robert R.
通讯作者：
Montgomery, Robert R.
影响因子：
10.4
作者：
Rodeghiero, F.;Tosetto, A.;Lillicrap, D.
通讯作者：
Lillicrap, D.
DOI：
10.1111/jth.15129
发表时间：
2021-01
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
DiGiandomenico S;Christopherson PA;Haberichter SL;Abshire TC;Montgomery RR;Flood VH;Zimmerman Program Investigators
通讯作者：
Zimmerman Program Investigators
影响因子：
20.3
作者：
Bellissimo, Daniel B.;Christopherson, Pamela A.;Montgomery, Robert R.
通讯作者：
Montgomery, Robert R.
影响因子：
5.7
作者：
Kitchen, Steve;Jennings, Ion;Preston, Francis E.
通讯作者：
Preston, Francis E.