PB0849 - Importance of VWF:CB assay in diagnosis of 2M VWD

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

DP

Dana Provaznikova, PhD (she/her/hers)

laboratory researcher
National Reference Laboratory for Disorders in Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic

Co-Author(s)

FM

Frantisek Marecek

laboratory scientist
National Reference Laboratory for Disorders in Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic
VG

Vera Geierova

physician
Center for Thrombosis and Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic
AR

Alena Radovska

laboratory technician
National Reference Laboratory for Disorders in Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic
MS

Martina Simonikova

laboratory technician
National Reference Laboratory for Disorders in Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic
RL

Renata Liskova

laboratory technician
National Reference Laboratory for Disorders in Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic
VP

Viera Pohlreichova

physician
Center for Thrombosis and Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic
IH

Ingrid Hrachovinova

head of laboratory
National Reference Laboratory for Disorders in Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic

Background: To establish diagnosis of von Willebrand disease (VWD) and its correct type is important for the treatment. VWF (von Willebrand factor):RCo and VWF:Ag are always investigated; however, VWF:CB is not a common assay. It can lead to 2M VWD be mistaken for type 1 or VWD is not diagnosed. Misdiagnosis could happen in type 2MBC VWD where VWF:CB is lower than VWF:RCo.

Aims: Correlation of 2MBC VWD genotype and phenotype in our patients.

Methods: In last three years, we have examined FVIII:C, VWF:Ag, VWF:RCo, VWF:CB, propeptide and multimeric structure of 43 patients from 29 families with VWD. Genomic DNA was analyzed by Sanger sequencing for vWF gene variants.

Results: Eight patients from four families were finally diagnosed as 2MBC VWD. A genetic variant was detected in all of them. We found two variants (R1399H, E1359K), that were in the A1 vWF domain and responsible for collagen binding. R1399H is a risk variant representing a hemorrhagic phenotype only in a homozygous state. The patient 1a with a homozygous R1399H would not be diagnosed correctly as VWD, if VWF:CB was not measured (VWF:CB 26 IU/dL, Table 1). Similar example was the patient 3. Interestingly, patients with the variant E1359K had unusually high VWF:CB, in average 173 IU/dL. These atypical values might be influenced by the methodology (HemosIL AcuStar VWF:CB). The patient 4a with this variant had border to normal values. In pregnancy shortly before delivery were VWF:RiCo 90 IU/dL and VWF:Ag 115 IU/dL. Despite these values she experienced a massive postpartum hemorrhage and had to be treated with vWF concentrate.

Conclusion(s): Our results confirmed the relevance of VWF:CB in the diagnosis of 2MBC VWD. We proved R1399H as an autosomal recessive mutation associated with 2MBC VWD. We will further study the cause of consistently higher values of VWF:CB in E1359K.