Frequency of Platelet type versus Type 2B von Willebrand Disease

Alexander Hamilton; Margareth Ozelo; Jayne Leggo; Colleen Notley; Hannah Brown; Juan Pablo Frontroth; Anne Angelillo-Scherrer; Fariba Baghaei; Said M. Enayat; Emmanuel Favaloro; David Lillicrap; Maha Othman

doi:10.1160/TH10-08-0523

Thrombosis and Haemostasis, Table of Contents

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

¹Laurentian University- St Lawrence College Collaborative Program, Kingston, Ontario, Canada

,

Margareth Ozelo

²Hemocentro UNICAMP, State University of Campinas, Brazil

,

Jayne Leggo

³Pathology and Molecular Medicine, Queen’s university, Kingston, Ontario, Canada

,

Colleen Notley

³Pathology and Molecular Medicine, Queen’s university, Kingston, Ontario, Canada

,

Hannah Brown

³Pathology and Molecular Medicine, Queen’s university, Kingston, Ontario, Canada

,

Juan Pablo Frontroth

⁴Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Servicio de Hematología/Oncología, Argentina

,

Anne Angelillo-Scherrer

⁵Service and Central Laboratory of Hematology, Centre Hospitalier Universitaire, Vaudois and University of Lausanne, Lausanne, Switzerland

,

Fariba Baghaei

⁶Department of Hematology and Coagulation, Sahlgrenska University Hospital, Sweden

,

Said M. Enayat

⁷Department of Haematology, The Birmingham Children’s Hospital, Birmingham, UK

,

Emmanuel Favaloro

⁸Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, New South Wales, Australia

,

David Lillicrap

³Pathology and Molecular Medicine, Queen’s university, Kingston, Ontario, Canada

,

Maha Othman

¹Laurentian University- St Lawrence College Collaborative Program, Kingston, Ontario, Canada

⁹Department of Anatomy and Cell Biology, Queen’s University, Kingston, Ontario, Canada

› Author Affiliations

Abstract

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

Full Text

References

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