Changing insights in the diagnosis and classification of autosomal recessive and dominant von Willebrand diseases 1980-2015

• 作者: Alain Gadisseur Angelika Batorova Inge Vangenechten Jan Jacques Michiels Miroslav Penka Petr Smejkal Tatiana Prigancova
• 来源期刊: 世界血液学杂志
• 学科: 医学
• 关键词: Von Willebrand disease Von Willebrand FACTOR ADAMTS13 DDAVP Von Willebrand FACTOR assays Von Willebrand gene MUTATIONS
• 年，卷（期）: 2016,（3）
• 页码范围: 61-74
• 页数: 14页
• 分类号: R

摘要

The European Clinical Laboratory and Molecular(ECLM)criteria define 10 distinct Willebrand diseases(VWD):recessive type 3,severe 1,2C and 2N;dominant VWD type 1 secretion/clearance defect,2A,2B,2E,2M and 2D;and mild type 1 VWD(usually carriers of recessive VWD).Recessive severe 1 and 2C VWD are characterized by secretion and multimerization defects caused by mutations in the D1-D2 domain.Recessive 2N VWD is a mild hemophilia due to D’-FVIII-von Willebrand factor(VWF)binding site mutations.Dominant 2E VWD caused by heterozygous missense mutations in the D3 domain is featured by a secretion-clearancemultimerization VWF defect.Dominant VWD type 2M due to loss of function mutations in the A1 domain is characterized by decreased ristocetin-induced platelet aggregation and VWF:RCo,normal VWF multimers and VWF:CB,a poor response of VWF:RCo and good response of VWF:CB to desmopressin(DDAVP).Dominant VWD type 2A induced by heterozygous mutations in the A2 domain results in hypersensitivity of VWF for proteolysis by ADAMTS13 into VWF degradation products,resulting in loss of large VWF multimers with triplet structure of each individual VWF band.Dominant VWD type 2B due to a gain of function mutation in the A1 domain is featured by spontaneous interaction between platelet glycoprotein Ib(GPIb)and mutated VWF A1 followed by increased proteolysis with loss of large VWF multimers and presence of each VWF band.A new category of dominant VWD type 1 secretion or clearance defect due to mutations in the D3 domain or D4-C1-C5 domains consists of two groups:Those with normal or smeary pattern of VWF multimers.