Genetic Testing Unravels Bleeding Disorders

A molecular approach is able to identify genes involved in life threatening bleeding disorders.

The rare platelet type of von Willebrand disease (PT-VWD) has similar diagnostic features to another form of the disease, 2B-VBD, and must be differentiated. A correct diagnosis can only be made by closely examining certain areas of both genes to determine where the defect lies.

An international team of scientists working in conjunction with the Queen's University, (Kingston, ON, Canada), analyzed a total of 110 samples/data from eight countries over a three year period. A molecular approach was utilized, analyzing exon 28 of the von Willebrand factor (VWF) gene, and in mutation negative cases the platelet glycoprotein Ib, alpha polypeptide (GP1BA) gene.

The investigators found that 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mutations consistent with a PT-VWD diagnosis, three had other VWD types (2A and 2M) and five expressed three previously unpublished exon 28 mutations. In this study, the percentage of type 2B VWD diagnosis is 44%, while the percentage of misdiagnosis of PT-VWD is 15%.

The study highlights the diagnostic limitations due to unavailability or poor application of radioimmunoprecipitation assays and related tests in some centers and proposes genetic analysis as a suitable tool for the discrimination of the two disorders worldwide. Accordingly, cases that are negative for both VWF and GP1BA gene mutations require further evaluation for alternative diagnoses.

Maha Othman, MD, PhD, a professor at Queen's University, said, "Correct diagnosis is critical because it determines the treatment decision." Despite its relative rarity, VWD is actually the most common genetically inherited bleeding disorder, affecting about 1% of the general population. The study was published online in February 2011 in Thrombosis and Haemostasis.

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