Platelets play a pivotal role in hemostasis, where their activation is tightly regulated by biochemical agonists such as thrombin, collagen, and adenosine diphosphate, all of which signal through calcium-mediated intracellular pathways. Under physiological conditions, this tightly controlled system ensures a rapid and localized response to vascular injury. During extracorporeal circulation, such as cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), platelets are instead exposed to artificial surfaces and abnormal flow dynamics. These artificial conditions introduce non-physiological forces, including elevated shear stress and turbulence, particularly across the oxygenator, which represents one of the most flow-restrictive and biologically active components of the circuit. Shear stress has long been recognized as a potent mechanical activator of platelets, capable of triggering intracellular calcium influx even in the absence of endothelial injury. This observation suggests that platelets circulating within CPB and ECMO circuits may become inappropriately activated purely as a function of circuit mechanics. Once activated, platelets may adhere to synthetic surfaces and form microaggregates, initiating a cascade of events that progressively impair oxygenator performance. As resistance within the oxygenator increases, transmembrane pressure rises, potentially culminating in a clinically relevant adverse event known as high-pressure excursion (HPE). HPE frequently necessitates oxygenator replacement, an intervention that carries procedural risk, interrupts support continuity, and increases both cost and circuit manipulation. Understanding the mechanisms underlying pressure excursions is therefore essential to improving extracorporeal support safety and durability.