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Thromb Haemost 2011; 105(03): 501-508
DOI: 10.1160/TH10-08-0523
Platelets and Blood Cells
Schattauer GmbH

Frequency of Platelet type versus Type 2B von Willebrand Disease

An international registry-based study
Alexander Hamilton
1   Laurentian University- St Lawrence College Collaborative Program, Kingston, Ontario, Canada
,
Margareth Ozelo
2   Hemocentro UNICAMP, State University of Campinas, Brazil
,
Jayne Leggo
3   Pathology and Molecular Medicine, Queen’s university, Kingston, Ontario, Canada
,
Colleen Notley
3   Pathology and Molecular Medicine, Queen’s university, Kingston, Ontario, Canada
,
Hannah Brown
3   Pathology and Molecular Medicine, Queen’s university, Kingston, Ontario, Canada
,
Juan Pablo Frontroth
4   Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Servicio de Hematología/Oncología, Argentina
,
Anne Angelillo-Scherrer
5   Service and Central Laboratory of Hematology, Centre Hospitalier Universitaire, Vaudois and University of Lausanne, Lausanne, Switzerland
,
Fariba Baghaei
6   Department of Hematology and Coagulation, Sahlgrenska University Hospital, Sweden
,
Said M. Enayat
7   Department of Haematology, The Birmingham Children’s Hospital, Birmingham, UK
,
Emmanuel Favaloro
8   Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, New South Wales, Australia
,
David Lillicrap
3   Pathology and Molecular Medicine, Queen’s university, Kingston, Ontario, Canada
,
Maha Othman
1   Laurentian University- St Lawrence College Collaborative Program, Kingston, Ontario, Canada
9   Department of Anatomy and Cell Biology, Queen’s University, Kingston, Ontario, Canada
› Author Affiliations Financial support: This work is supported by a two year research grant from the Canadian Hemophilia Society (CHS).
Further Information

Publication History

Received: 11 August 2010

Accepted after major revision: 27 February 2010

Publication Date:
27 November 2017 (online)

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Summary

Less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD) worldwide. Several reports have discussed the diagnostic challenge of this disease versus the closely similar disorder type 2B VWD. However, no systematic study has evaluated this dilemma globally. Over three years, a total of 110 samples/data from eight countries were analysed. A molecular approach was utilised, analysing exon 28 of the von Willebrand factor (VWF) gene, and in mutation negative cases the platelet GP1BA gene. Our results show that 48 cases initially diagnosed as putative type 2B/PT-VWD carried exon 28 mutations consistent with type 2B VWD, 17 carried GP1BA mutations consistent with a PT-VWD diagnosis, three had other VWD types (2A and 2M) and five expressed three non-previously published exon 28 mutations. Excluding 10 unaffected family members and one acquired VWD, 26 cases did not have mutations in either genes. Based on our study, the percentage of type 2B VWD diagnosis is 44% while the percentage of misdiagnosis of PT-VWD is 15%. This is the first large international study to investigate the occurrence of PT-VWD and type 2B VWD worldwide and to evaluate DNA analysis as a diagnostic tool for a large cohort of patients. The study highlights the diagnostic limitations due to unavailability/poor application of RIPA and related tests in some centres and proposes genetic analysis as a suitable tool for the discrimination of the two disorders worldwide. Cases that are negative for both VWF and GP1BA gene mutations require further evaluation for alternative diagnoses.

Keywords

VWF- A1 domain - platelets - RIPA - VWF multimers - type 2B VWD - GP1BA - rare bleeding disorders - platelet function defect
 

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