Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder caused by the absence or the dysfunction of the αIIbβ3 integrin, the most abundant receptor on platelets that mediates platelet aggregation through its binding of adhesive proteins. GT is readily identifiable by platelet function testing, and a lack of platelet aggregation in response to all physiological agonists is unique for this disease. The ITGA2B gene encodes for the αIIb subunit, whereas the ITGB3 gene encodes for β3. Mutations causing GT can affect either ITGA2B or ITGB3. The disease is characterized by spontaneous and trauma-related mucocutaneous bleeding, with variable expression ranging from easy bruising to fatal hemorrhages. Platelet transfusions are used to control or prevent life-threatening blood loss, but can become ineffective due to naturally occurring antibodies directed against αIIbβ3. Such antibodies are produced when patient's immune system comes into contact with normal αIIbβ3 expressing platelets.~There is no currently consensus concerning the frequency, the long-term evolution, or the formation of characteristics of antibodies from GT patients in relation to the nature of the defective gene (ITGA2B or ITGB3), gene variations or other factors. Research are needed to confirm that nature of the gene defect may have a causative role in antibody development. Moreover, strength and persistence of antibodies may vary among patients with the same mutation, suggesting that other factors, such as immune modifiers genes, play a role in shaping antibody repertoire.~Monoclonal antibody-specific immobilization of platelet antigens (MAIPA) is still considered as the reference method for evaluating the presence of anti-αIIbβ3 antibodies in GT patients. All the tests will be performed by the principal investigator site (Bordeaux).
This project aim to correlate risk factors (genetic, therapeutic and socio-demographic factors) to anti-αIIbβ3 antibodies formation following blood products transfusion (platelets or packed red cells) or pregnancy in a national cohort of GT patients.