Identifying type Vicenza von Willebrand disease

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Type Vicenza von Willebrand disease (VWD) is characterized by increased clearance of von Willebrand factor (VWF).
• This VWD type presents with discrepancies between plasma and platelet VWF levels and unusually large VWF multimers.
• Diagnosing type Vicenza VWD can be difficult due to its heterogeneous clinical presentation.

Purpose of the Study:

• To establish diagnostic criteria for identifying type Vicenza VWD in a large patient cohort.
• To investigate the utility of comparing plasma and platelet VWF levels for VWD subtyping.
• To correlate genetic mutations with clinical phenotype in type Vicenza VWD.

Main Methods:

• Selection of candidate patients based on low plasma VWF and normal platelet VWF levels.
• Exclusion of patients with type 2A and 2B VWD.
• Genetic analysis to identify specific VWF mutations.
• Assessment of VWF survival and VWF multimer analysis.

Main Results:

• Eighteen candidate patients were identified using the defined criteria.
• Fifteen patients (from 5 families) were confirmed as type Vicenza VWD through genetic analysis.
• Most type Vicenza VWD patients carried both G2220A and G3614A mutations; one patient had only the G3614A mutation.
• All patients exhibited reduced VWF survival; ultralarge VWF multimers were present in all but one patient.

Conclusions:

• Low plasma VWF combined with normal platelet VWF content serves as a valuable initial indicator for type Vicenza VWD.
• This diagnostic approach can aid in identifying patients with this specific VWD subtype.
• Genetic confirmation and phenotypic analysis are crucial for definitive diagnosis and understanding disease mechanisms.