Platelet adhesive protein defect disorders

Introduction The investigation of platelet defects causing bleeding disorders has been an important step in determining the roles of the major glycoproteins in platelet function. In particular, Bernard–Soulier syndrome and Glanzmann's thrombasthenia have provided the basis for studying the function of the GPIb complex and α IIb β 3 , respectively. More recently, some generally milder bleeding disorders have been related to the absence or deficiency of other platelet receptors. With the development of techniques to produce mice in which specific gene expression has been deleted, these defects can also be reproduced and can be corrected by gene therapy. Have the disorders in humans still lessons to teach us? Probably the main diseases have already been discovered but we cannot exclude that a detailed screening of patients with mild, platelet related, bleeding disorders might disclose defects in previously unknown minor platelet receptors or new mutations with different effects in known receptors. Many patients with mild bleeding problems related to platelets are seen in hematology departments and cannot yet be diagnosed at a molecular level. Achieving the ability to diagnose the defects in these patients is still a major goal in platelet studies and may be amenable to proteomics approaches. Until X-ray crystallographic structures are available for the GPIb complex and α IIb β 3 , information provided by the molecular diagnosis of Bernard–Soulier syndrome and Glanzmann's thrombasthenia will continue to provide important data on structure– functional relationships.