Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Hematology, PLATELET DISORDERS, DEFECTS, ALPHA-IIB-BETA-3, VARIANTS, ASSOCIATION, EXPRESSION, GUIDELINES, MANAGEMENT, MUTATIONS, DIAGNOSIS, Blood Platelets, Humans, Integrin beta3, Platelet Aggregation, Platelet Function Tests, Platelet Glycoprotein GPIIb-IIIa Complex, Thrombasthenia, ClinGen Platelet Disorder Variant Curation Expert Panel, Cytogenetics and Molecular Genetics, Disorders of Platelet Function, Laboratory Hematology, Platelets, 1102 Cardiorespiratory Medicine and Haematology, Immunology, 3201 Cardiovascular medicine and haematology

Abstract:

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and β3. These integrins are encoded by the ITGA2B and ITGB3 genes and form platelet glycoprotein (GP)IIb/IIIa, which acts as the principal platelet receptor for fibrinogen. Although there is variability in the clinical phenotype, most patients present with severe mucocutaneous bleeding at an early age. A classic pattern of abnormal platelet aggregation, platelet glycoprotein expression and molecular studies confirm the diagnosis. Management of bleeding is based on a combination of hemostatic agents including recombinant activated factor VII with or without platelet transfusions and antifibrinolytic agents. Refractory bleeding and platelet alloimmunization are common complications. In addition, pregnant patients pose unique management challenges. This review highlights clinical and molecular aspects in the approach to patients with GT, with particular emphasis on the significance of multidisciplinary care.