PB0071 - Von Willebrand disease classification- a comparative study of functional assay testing in a tertiary haematology unit

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Caitlin Rice, MB Bch BAO DTMH MRCP

Haematology Research Fellow
Fiona Stanley Hospital, Perth, Western Australia
Perth, Australia, Western Australia, Australia

Co-Author(s)

LK

Lisa Kaminskis

Medical Scientist
PathWest Coagulation Laboratory, Fiona Stanley Hospital, Perth, Western Australia, Australia
Perth, Western Australia, Australia
NM

Natasha Modica

Medical Scientist
PathWest Coagulation Laboratory, Fiona Stanley Hospital, Perth, Western Australia, Australia
Perth, Western Australia, Australia
JT

Jim Tiao

Senior Medical Scientist
PathWest Molecular Laboratory, Fiona Stanley Hospital
Perth, Western Australia, Australia
Dominic Pepperell

Haematology Consultant
Department of Thrombosis and Haemostasis, Fiona Stanley Hospital, Perth, Western Australia, Australia
Perth, Western Australia, Australia
SP

Stephanie P'ng

Haematologist
The Haemophilia and Haemostasis Centre, Fiona Stanley Hospital, Murdoch, Australia
Murdoch, Western Australia, Australia

Background:

Background: The diagnostic algorithm of von Willebrand disease (VWD) requires measurement of VWF antigen (VWF:Ag) and ristocetin cofactor (VWF:RicoF). The introduction of direct GPIba-binding assays may become the functional assay of choice. Molecular genetic testing can provide additional benefit particularly in type 2 and 3 VWD.

Aims:

Aims: Assessment of the INNOVANCE® VWF Ac assay against existing assays for accurate diagnosis of VWD.

Methods:

Methods: Samples from patients with Type 1,2 VWD, acquired VWD and haemophilia were tested with the VWF Ag assay, VWF:RicoF both turbidimetric assays on the Sta-R Max analyser and the INNOVANCE® VWF Ac assay, a turbidimetric latex based agglutination assay using recombinant GP1b with 2 gain of function mutations. A ratio of 0.7 was used to distinguish type 1 from type 2 VWD.

Results:

Results: Currently 49 samples were assayed with overall good correlation between the VWF:RicoF and VWF: Ac (ROC curve 0.72 ) (Figure 1). There were 6 samples with discrepant ratios: 1 sample was classified Type 1 VWD using the VWF:GP1bM/VWF Ag ratio versus Type 2 using the VWF:RicoF/VWF Ag ratio (Table 1). This patient had Type 2 VWD and a mutation in exon 28 of VWF, in the A2 ADAMTS13 binding domain. 1 Haemophilia A patient had all assay levels within normal range. 4 remaining samples had VWF:RicoF/VWF Ag ratios close enough to 0.7 that classification would change if the VWF:RicoF result varied as much as the known CV of 13-34%.

Conclusion(s): Conclusion(s): The INNOVANCE® VWF Ac assay showed overall good correlation with the existing VWF: RicoF Assay however misclassification can occur in certain patients with mutations in the A2 binding domain of the VWF antigen. The gain of function mutations in the GP1bM may compensate for certain mutations leading to normalisation of results and misclassification as Type 1 versus Type 2 VWD.