Redox Control in Platelet Activity and Therapy

Maintaining redox balance is essential for platelet physiology and overall cellular homeostasis. Upon activation, platelets generate reactive oxygen species (ROS), which act as signaling mediators in responses to collagen and are required for collagen-dependent thrombus formation. Multiple enzymatic systems contribute to platelet ROS production, with nicotinamide adenine dinucleotide (phosphate) oxidases (NOX isoforms) serving as the primary source, complemented by cyclooxygenase (COX), xanthine oxidase (XO), and the mitochondrial respiratory chain. Both oxidative and reductive stress disrupt this equilibrium and have been implicated in the pathophysiology of diverse diseases, including bleeding disorders, thrombosis, cardiovascular disorders, diabetes and cancer. In transfusion medicine, mitochondrial dysfunction and the resulting oxidative stress are key drivers of platelet lesion resulting in clearance defects and the progressive loss of hemostatic activity during storage. Targeting platelet-specific redox regulatory pathways represents a promising strategy to better define platelet contributions to human health and to develop interventions that may alter disease outcomes in which platelets play a central role.