Collagen Binding Provides a Sensitive Screen for Variant von Willebrand Disease
Collagen Binding Provides a Sensitive Screen for Variant von Willebrand Disease
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DOI：
10.1373/clinchem.2012.199000
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发表时间：
2013-04-01
影响因子：
9.3
通讯作者：
Haberichter, Sandra L.
中科院分区：
文献类型：
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作者：
Flood, Veronica H.;Gill, Joan Cox;Haberichter, Sandra L.
背景：血管性血友病因子（VWF）是一种多聚体蛋白，可结合血小板和胶原蛋白，促进血管损伤部位的止血。测量VWF多时间分布对于变异型血管性血友病（VWD）的诊断至关重要，特别是2A型和2B型，但典型的凝胶电泳测量在技术上困难且耗时。比较VWF胶原结合（VWF: CB）和VWF多时间分布，以评估VWF: CB作为诊断试验的效用。方法：参与者参加了齐默尔曼VWD分子和临床生物学项目。用琼脂糖凝胶电泳分析VWF: CB的III型胶原和多聚体分布。研究人群包括146名健康对照者、351名1型VWD患者和77名2型VWD患者。使用Mann-Whitney检验评估参考区间内（对照）和参考区间外多组结果个体之间的差异。结果：参考区间内多计时器分布个体VWF: CB/VWF抗原比值均值为1.10，参考区间外多计时器分布个体VWF: CB/VWF抗原比值均值为0.51 （P < 0.001）。当VWF: CB/VWF抗原切断比为0.6时，VWF: CB对健康对照组多时间异常的敏感性为100%，对1型VWD患者的敏感性为99%，对2A型和2B型VWD患者的敏感性为100%，当VWF: CB/VWF抗原切断比为0.7时，对所有患者的敏感性降至99%。除了具有新突变或未分类突变的个体外，VWF: CB能够正确地对具有变异VWD的参与者进行分类。结论：这些研究结果表明，VWF: CB可以替代初始VWD检测中的多时间分布，尽管还需要进一步的研究来验证VWF: CB的临床应用。(C) 2012美国临床化学学会
BACKGROUND: von Willebrand factor (VWF) is a multimeric protein that binds platelets and collagen, facilitating hemostasis at sites of vessel injury. Measurement of VWF multimer distribution is critical for diagnosis of variant von Willebrand disease (VWD), particularly types 2A and 2B, but the typical measurement by gel electrophoresis is technically difficult and time-consuming. A comparison of VWF collagen binding (VWF: CB) and VWF multimer distribution was performed to evaluate the utility of VWF: CB as a diagnostic test.METHODS: Participants were enrolled in the Zimmerman Program for the Molecular and Clinical Biology of VWD. VWF: CB was analyzed with type III collagen and multimer distribution by agarose gel electrophoresis. The study population included 146 healthy controls, 351 individuals with type 1 VWD, and 77 with type 2 VWD. Differences between individuals with multimer group results within (controls) and outside the reference intervals were assessed with Mann-Whitney tests.RESULTS: The mean VWF: CB/VWF antigen ratio was 1.10 for individuals with multimer distribution within the reference intervals and 0.51 for those with multimer distribution outside the reference intervals (P < 0.001). Sensitivity of VWF: CB for multimer abnormalities was 100% for healthy controls, 99% for patients with type 1, and 100% for patients with type 2A and type 2B VWD using a VWF: CB/VWF antigen cutoff ratio of 0.6, and decreased to 99% for all patients with a ratio of 0.7. With the exception of individuals with novel or unclassified mutations, the VWF: CB was able to correctly categorize participants with variant VWD.CONCLUSIONS: These findings suggest that VWF: CB may substitute for multimer distribution in initial VWD testing, although further studies are needed to validate the clinical utility of VWF: CB. (C) 2012 American Association for Clinical Chemistry