Laboratory Diagnosis and Molecular Basis of Mild von Willebrand Disease Type 1

Abstract

Mild type 1 von Willebrand disease (VWD) is characterized by low to variable penetrance of bleeding, a high (increased) prevalence of blood group O, von Willebrand factor (VWF) values around and above 30% with normal ratios of VWF:ristocetin cofactor activity (RCo)/VWF:antigen (Ag), VWF:collagen binding (CB)/VWF:Ag and factor VIII (FVIII):coagulant activity (C)/VWF:Ag. Within this group of patients, the combination of the C1584 mutation and blood group O is rather frequent. Patients with mild VWD type 1 present good/normal responses of FVIII:C and VWF parameters to desmopressin (DDAVP). With the exclusion of dominant VWD type Vicenza, type 1/2E, recessive 2N and dominant 2M, missense mutations in patients with mild VWD type 1 with normal multimers are mainly located in the regulatory sequence region, the D1/D2 propeptide region, the D′ VWF-FVIII binding site region and the D4, B1–B3 and C1–C2 domains but rarely in the D3, A1 or A2 domain. A new category of either dominant or recessive mild VWD type 1 due to mutations in the D4, B1–B3 and C1–C2 domains of the VWF gene consists of two groups: one group with mild VWD with normal VWF multimers and a second group with mild/moderate VWD with smeary multimer pattern.