Journal of Blood Medicine (Jul 2021)
Profiling the Genetic and Molecular Characteristics of Glanzmann Thrombasthenia: Can It Guide Current and Future Therapies?
Abstract
Alan Nurden Institut Hospitalo-Universitaire LIRYC, Pessac, FranceCorrespondence: Alan NurdenInstitut Hospitalo-Universitaire LIRYC, Pessac, 33600, FranceEmail [email protected]: Glanzmann thrombasthenia (GT) is the most widely studied inherited disease of platelet function. Platelets fail to aggregate due to a defect in platelet-to-platelet attachment. The hemostatic plug fails to form and a moderate to severe bleeding diathesis results. Classically of autosomal recessive inheritance, GT is caused by defects within the ITGA2B and ITGB3 genes that encode the αIIbβ 3 integrin expressed at high density on the platelet surface and also in intracellular pools. Activated αIIbβ 3 acts as a receptor for fibrinogen and other adhesive proteins that hold platelets together in a thrombus. Over 50 years of careful clinical and biological investigation have provided important advances that have improved not only the quality of life of the patients but which have also contributed to an understanding of how αIIbβ 3 functions. Despite major improvements in our knowledge of GT and its genetic causes, extensive biological and clinical variability with respect to the severity and intensity of bleeding remains poorly understood. I now scan the repertoire of ITGA2B and ITGB3 gene defects and highlight the wide genetic and biological heterogeneity within the type II and variant subgroups especially with regard to bleeding, clot retraction, the internal platelet Fg storage pool and the nature of the mutations causing the disease. I underline the continued importance of gene profiling and biological studies and emphasize the multifactorial etiology of the clinical expression of the disease. This is done in a manner to provide guidelines for future studies and future treatments of a disease that has not only aided research on rare diseases but also contributed to advances in antithrombotic therapy.Keywords: Glanzmann thrombasthenia, inherited platelet disorder, bleeding syndrome, integrin, gene profiling, mutation analysis
