Apoptotic Events in Type-I Glanzmann Thrombasthenia Platelets

Background: Activated normal platelets undergo numerous biochemical and morphological changes, some of which are apoptotic. Phosphatidylserine (PS) expression, Δψm depolarization, microparticle (MP) formation, platelet shrinkage, release of cytochrome c, and caspase activation are hallmarks of both platelet activation and apoptosis. In this study, we report the apoptotic responses of type-I Glanzmann thrombasthenic platelets. Materials and Methods: Platelets from twelve unrelated patients with type I Glanzmann thrombasthenia were examined as washed platelets. Calcium ionophore A23187 was used as an agonist to activate the platelets. Flow cytometry was employed to detect phosphatidylserine expression (Annexin A5 Alexa Fluor), Δψm depolarization (JC-10), platelet-derived MP formation (forward scatter; events <1.0 µm in size), and platelet shrinkage (mean-FSC). Anti-CD42b was used as a platelet-specific marker to distinguish platelets from other particles. Results: We determined that increased cytosolic calcium significantly increased PS exposure, depolarized mitochondrial inner membrane potential (Δψm), increased microparticle formation, and induced platelet shrinkage in type-I Glanzmann thrombasthenic platelets. Our research showed that type I Glanzmann thrombasthenic platelets exhibit characteristics of platelet apoptosis. GPIIbIIIa deficiency does not limit platelet activation or apoptosis. Conclusion: We conclude that GPIIb-IIIa-independent mechanisms may be involved in the normal apoptosis of thrombasthenic platelets. Our data deepen the understanding of the role of the platelet fibrinogen receptor in revealing aspects of normal apoptosis. However, this may help explain the normal platelet count among thrombasthenic patients.