2N 型血管性血友病：特征与诊断难点。

Type 2N von Willebrand disease: Characterization and diagnostic difficulties.

机构信息

Department of Medicine, Hemorrhagic and Thrombotic Disorders Unit, University of Padua Medical School, Padua, Italy.

出版信息

Haemophilia. 2018 Jan;24(1):134-140. doi: 10.1111/hae.13366. Epub 2017 Nov 8.

DOI:10.1111/hae.13366

PMID:29115006

Abstract

INTRODUCTION

An abnormal factor VIII (FVIII) binding capacity of von Willebrand factor (VWF) identifies type 2N von Willebrand disease (VWD). Type 2N VWD patients are identified by means of the VWF FVIII binding (VWF:FVIIIB) assay, and especially their VWF:FVIIIB/VWF:Ag ratio (VWF:FVIIIB ratio).

AIM

We report on our 15-year experience of diagnosing type 2N VWD.

METHODS

We have performed 2178 VWF:FVIIIB assays in bleeders and normal subjects.

RESULTS

von Willebrand factor (VWF):FVIIIB was reduced in 682, but only 60 had low VWF:FVIIIB ratios (<0.74). Among nine patients who had a VWF:FVIIIB ratio below 0.3, four had normal VWF levels and were homozygotes for the p.R854Q mutation; the other five had low VWF levels due to a quantitative VWF mutation combined with p.R854Q. The VWF:FVIIIB ratio ranged between 0.3 and 0.73 in 51 subjects; 34 of them were heterozygotes for the p.R854Q mutation, while one carried the p.R760C. The heterozygotes for type 2N included subjects with or without bleeding symptoms, the former with significantly lower mean VWF levels than the latter. Among the 116 normal subjects tested, six were heterozygotes for the p.R854Q mutation (all asymptomatic).

CONCLUSIONS

The prevalence of type 2N in our VWD cohort was 2.5%, and 5.2% of the general population in Northeast Italy was found heterozygous for the p.R854Q mutation. It might be difficult to reveal a type 2N defect using routine tests alone, especially when it is combined with a quantitative VWF mutation. Accordingly, we always recommend VWF:FVIIIB assay in the diagnostic workup of VWD.

摘要

简介

血管性血友病因子（VWF）与因子 VIII（FVIII）结合能力异常可确定 2N 型血管性血友病（VWD）。2N 型 VWD 患者通过 VWF FVIII 结合（VWF：FVIII）检测来识别，特别是他们的 VWF：FVIII/VWF：Ag 比值（VWF：FVIII 比值）。

目的

我们报告了我们在诊断 2N 型 VWD 方面的 15 年经验。

方法

我们对出血患者和正常受试者进行了 2178 次 VWF：FVIII 检测。

结果

VWF：FVIII 降低见于 682 例，但仅有 60 例 VWF：FVIII 比值较低（<0.74）。在 9 例 VWF：FVIII 比值低于 0.3 的患者中，有 4 例 VWF 水平正常且为 p.R854Q 突变的纯合子；另外 5 例 VWF 水平较低，原因是定量 VWF 突变合并 p.R854Q。51 例患者的 VWF：FVIII 比值在 0.3 至 0.73 之间；其中 34 例为 p.R854Q 突变的杂合子，1 例为 p.R760C。2N 型的杂合子包括有或无出血症状的患者，前者的平均 VWF 水平明显低于后者。在 116 名接受测试的正常受试者中，有 6 人为 p.R854Q 突变的杂合子（均无症状）。