The Role of Age in Shear-Induced Platelet Activation: A Comparison of Neonatal Cord and Adult Platelet

The relationship between age and platelet activation is currently not well understood. Experiments have been done evaluation neonatal platelet activation in comparison to adults, and these studies have shown that neonatal platelets are hypoactive when activated via biochemical agonists. In addition, neonatal platelets have shown to have impaired calcium mobilization and release upon activation. Despite these abnormalities, neonatal platelets have shown to aggregate similarly to adult platelets under flow conditions. It is important to note that none of these studies have evaluated neonatal platelet activation with high shear stresses as an agonist. Because of this it is currently not known if neonatal platelets retain their hypoactive properties when activated by a mechanical agonist. Elucidating such a mechanism would provide inside into the role that platelet age plays in shear induced activation, and this knowledge can potentially be translated into the development of new therapeutics to replace the harsh anticoagulants that cardiovascular disease patients take.;The overall goal of this thesis was to provide an exploratory study into the role that age plays in shear induced platelet activation. This was done by comparing thrombin generation, platelet surface marker expression, and activation due to the inhibition of intracellular and extracellular calcium in adult and neonatal cord platelets under high shear conditions. The results from these studies show that neonatal and adult platelets have similar thrombin generation under various shear conditions. Differences observed between neonatal cord and adult platelet Annexin V binding under high shear conditions may suggest a difference in the platelet membrane sensitivity of neonatal platelets when compared to the control. In addition, it was showed the chelation of intracellular calcium and the removal of extracellular calcium do not affect neonatal or adult platelet thrombin generation or Annexin V expression under high shear conditions.