Canadian platelet-type von Willebrand disease (PT-VWD) project: progress and update
Abstract number: OC-WE-134
Othman1 M., Ozelo1 M.C., Brown1 H., Leggo1 J., Notley1 C., Favaloro2 E.J., Enayat3 S., Frontroth4 J.P., Angelillo5 A., Smith6 H., Olson7 J., Lillicrap1 D.
11Pathology and Molecular Medicine, Queen's University, Kingston, Canada 22Institute of Clinical Pathology and Medical research, Westmead Hospital, Westmead, Australia 33Department of Haematology, Birmingham Children's Hospital, Birmingham, UK 44Hematology, Pediatric hospital, Buenos Aires, Argentina 55Service and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland 66Tuft Medical centre, Tuft medical centre, Boston 77Department of Pathology, Clinical Laboratories, UHS, UTHSCSA, San Antonio, TX, USA
How-to-cite Othman M, Ozelo MC, Brown H, Leggo J, Notley C, Favaloro EJ, Enayat S, Frontroth JP, Angelillo A, Smith H, Olson J, Lillicrap D. Canadian platelet-type von Willebrand disease (PT-VWD) project: progress and update. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract OC-WE-134
We report updated findings from the Canadian PT-VWD project (http://www.pt-vwd.org) investigating the diagnostic dilemma of type 2B VWD and the closely similar disorder PT-VWD. We have recruited a total of 82 cases over the past two years: 33 from Canada and 49 others worldwide: Brazil (8), Australia (16), UK (15), Argentina (6), Switzerland (3), USA (1). All patients were provisionally diagnosed as either type 2B VWD or PT-VWD. Genetic analysis of exon 28 VWF revealed known type 2B mutations in 22/33 in Canada and in 21/49 worldwide (commonest V1316M and R1306M). Platelet GP1BA analysis in VWF mutation negative cases revealed known PT-VWD mutations in 17 cases: Canada (2), UK (12), Australia (3). 20/ 82 cases had no mutations in either exon 28 of VWF or in GP1BA. One case proved to have an acquired type 2B-like VWD phenotype. In the Canadian cases, 1 had R1597W (2A mutation), 1 had R1315C (2A/2M/Unclassified mutation) and 5 others showed 3 novel mutations (L1460F, C1363Y, E1389K). 1 Brazilian case showed R1374H (2M/ Unclassified mutation). Genetic analysis for the Australian, UK cases was performed at the country of origin and the Argentineans at Milwaukee, USA. 3 Australian cases were phenotypically proved as PT-VWD based on RIPA mixing assays prior to genetic confirmation, and in 12 UK cases, cryoprecipitate challenge indicated PT-VWD prior to the confirmatory genetic testing. All 6 unrelated Argentinean cases showed enhanced RIPA with negative cryoprecipitate test (only 3 had 2B mutations). Excluding non-affected relatives of type 2B VWD cases, the prevalence of non-type 2B/non PT-VWD cases remains relatively high. This may reflect a) misdiagnosis of type 2B VWD due to lack or misinterpretation of tests such as RIPA and platelet mixing studies, b) Possible type 2B /PT-VWD phenotypic variants. Further recruitment of samples/data is critical to evaluate this diagnostic dilemma and to validate treatment decisions.
Disclosure of interest: none declared.
