期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 7, 期 11, 页码 1832-1839出版社
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1538-7836.2009.03594.x
关键词
bleeding; platelet glycoprotein Ib; ristocetin; von Willebrand disease; von Willebrand factor
资金
- National Institutes of Health [P01 HL081588, HL33721, HL044612]
- National Hemophilia Foundation
- Hemophilia and Thrombosis Research Society
Background: Type 2M von Willebrand disease (VWD) is characterized by a qualitative defect in von Willebrand factor (VWF) and diagnosed by a disproportionate decrease in VWF ristocetin cofactor activity (VWF:RCo) as compared with VWF antigen (VWF:Ag). Objective: We report here on the spurious diagnosis of VWD in a patient with a sequence variation in the ristocetin-binding domain of VWF. Patients/methods: The index case had a VWF:RCo of 11 IU dL-1, with VWF:RCo/VWF:Ag ratio of 0.09. DNA sequencing revealed a novel P1467S mutation in a known ristocetin-binding region of the A1 domain. Because of the discrepancy between the laboratory findings, consistent with type 2M VWD, and the patient's lack of bleeding symptoms, further studies were performed to determine whether this mutation affected VWF function or merely reduced its ability to interact with ristocetin. Results: Studies with recombinant VWF showed normal platelet binding with botrocetin, but a significant decrease in binding in response to ristocetin. Ristocetin-induced binding to recombinant GPIb was also absent, but normal binding was seen when a gain-of-function GPIb construct was used in the absence of ristocetin. VWF function under shear stress was normal when analyzed with a cone and plate(let) analyzer. Conclusions: The decreased VWF:RCo seen with the P1467S sequence variation likely represents an artifact as a result of the use of ristocetin to measure VWF activity. The normal VWF function in other assays correlates with the lack of hemorrhagic symptoms, and suggests the need for more physiologically relevant assays of VWF function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据