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

Table 1 Classification of von Willebrand disease according to International Society on Thrombosis and Haemostasis guidelines 1994-2007[13-15]

1 Inherited VWD caused by genetic mutations at the VWF locus includes a broad spectrum of recessive and dominant variants of VWD

2 WD Type 1 is quantitative deficiency of VWF mainly based on a normal VWF:RCo/VWF:Ag ratio. Type 2 VWD is a qualitative deficiency of VWF as documented by a decreased VWF:RCo/VWF:Ag ratio. Type 3 refers to virtually complete deficiency of VWF

3 VWD Type 2 refers to qualitative variants with absence of high molecular weight VWF multimers and distinguishes 2A (IIA, IIB, IIE, and IID) 2B, 2M and 2 N

4 VWD Type 2M or 2U is a distinct entity with decreased platelet dependent function (VWF:RCo) and presence of large VWF multimers

5 VWD Type 2A (IIA, IIC, IIE and IID) refers to qualitative variants with absence of HMW multimers, normal or decreased RIPA and decreased VWF: VWF:RCo/VWF:Ag ratio

6 VWD Type 2B is a qualitative variant with absence of HMW multimers, decreased VWF:RCo/VWF:Ag ratio and increased RIPA

7 VWD Type 2N is a mild hemophilia due to FVIII binding defect of VWF, presence of large VWF multimers, normal VWF:RCo/VWF:Ag ratio and decreased FVIII/VWF:Ag ratio

VWD: Von Willebrand disease; VWF: Von Willebrand factor; RIPA: Ristocetin-induced platelet aggregation.