Summary
Specific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system,
including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet
adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays
a pivotal role since platelet aggregation is exclusively mediated by this receptor
and its interaction with soluble macromolecular proteins. Inherited defects of the
GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders,
known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von
Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques,
rapid advances in our understanding of the molecular genetic basis of these disorders
have been made during the last few years. Moreover, analyses of patients with congenital
platelet membrane glycoprotein abnormalities have provided valuable insights into
molecular mechanisms that are required for structural and functional integrity, normal
biosynthesis of the glycoprotein complexes and coordinated membrane expression of
their constituents. The present article reviews the current state of knowledge of
the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding
manifestations and established diagnostic criteria for each of these dis-orders are
summarized. In particular, the variety of molecular defects that have been identified
so far and their genetic basis will be discussed.
Keywords
Membrane glycoprotein receptors - Glanzmann's thrombasthenia - Bernard-Soulier syndrome
- Platelet-type von Willebrand's disease
