The role of post-transcriptional modifications, such as O-glycosylation and N-glycosylation, in platelet biology and disease is poorly understood. This session will elucidate how alterations in glycan expression alter platelet homeostasis. Individuals with Tn syndrome that results from altered O-glycan expression, the so-called Tn antigen, due to a somatic mutation develop thrombocytopenia. Recently, a genetically modified mouse strain that resembles the human Tn syndrome showed that O-glycans are not only required for hemostatic platelet functions but also for platelet production. Specific anti-platelet antibodies associated with immune thrombocytopenia induce desialyation of the target glycoprotein, causing platelet activation and apoptosis leading to platelet clearance. Platelets lacking sialic acid serve as communicators between the hepatic Ashwell Morell receptor to stimulate thrombopoietin production and to regulate bone marrow homeostasis.
These studies reinforce the notion that glycans harbor biological information altering both platelet production and destruction under steady state and pathologic disorders.