Thrombocytes, more often referred to as platelets, are a key component of blood whose primary function is to maintain hemostasis by rapidly plugging any interruptions in the vasculature, a process known as clotting. Clotting begins with damage to the endothelium, causing platelets to activate and bind to the endothelial cells or underlying exposed extracellular matrix proteins. Platelet margination and binding to the vascular wall is promoted through hemodynamic, heterogenous collisions between cellular components, including deformable red blood cells (RBCs) in the RBC core. However, RBCs can undergo membrane rigidity in blood-related diseases, such as sickle cell disease (SCD). Experimental research has shown that artificially rigidified RBCs lead to an expanded RBC core and significantly impact white blood cell (WBC) adhesion to the endothelium. However, little experimental work exists to fully elucidate the effect of rigid RBCs on platelet margination and binding in vessels. We utilized an in vitro flow-based system to examine how the extent of rigidification and rigid RBC concentration affect platelet margination and binding to a damaged endothelium model mimicking acute vascular damage. RBCs were removed from the whole blood and artificially rigidified using a peroxide solution. The RBCs were then reconstituted into blood and perfused over the damaged endothelium. Platelet adhesion was quantified and compared to a healthy control. The presence of rigid RBCs in flow drastically increases platelet adhesion under specific rigidities and concentrations. This finding suggests that rigid RBCs may play a major role in disrupting normal hemodynamics and contributing to the pervasive vaso-occlusive crises that occur in many SCD patients. Overall, we will elucidate how rigid RBC-platelet interactions affect platelet binding, a critical step in hemostasis. This study can help determine the mechanism causing vaso-occlusive events in SCD patients and can form the basis of the study of platelet-cell dynamics in the future.

Effect of rigid red blood cells on platelet adhesion in flow

2019 Fall National Meeting

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