Tranexamic acid impact on platelet adhesion to the endothelium after shock conditions: A protective effect?

Abstract

Trauma and hemorrhagic shock lead to microcirculatory disturbances related to endothelial injury and endothelial glycocalyx (EG) degradation. Improved outcomes following trauma and hemorrhagic shock have been linked to protection of the EG layer, which is a topic of increasing investigation. Early tranexamic acid (TXA) administration following trauma and hemorrhagic shock improves outcomes in clinic studies. Recent translational studies have also shown that early TXA administration protects the EG following shock insults; the impact on blood-endothelial cell interactions is unknown. Platelet adherence to vascular endothelium may contribute to microcirculatory disturbances; the effects of TXA on this phenomenon are uncertain. Microfluidic devices have been used to study the behavior of endothelial cells and platelets under flow conditions. We hypothesize that the protective effect of TXA against EG degradation would prevent shock-induced platelet adhesion to the microvasculature. This was studied in a microfluidic cell culture model under a controlled microenvironment. Microfluidic endothelial cell cultures were exposed to flow conditions under control or hypoxia-epinephrine exposure. Tranexamic acid was added to the perfusate at various times in control and experimental groups. Endothelial glycocalyx thickness, degradation products, and platelet adhesion to the endothelium were measured. Tranexamic acid protected the glycocalyx from degradation following hypoxia-reoxygenation-epinephrine exposure. Platelet adhesion to the endothelium was significantly reduced by TXA in a time sensitive manner. Tranexamic acid may protect the microvasculature from perfusion abnormalities following shock conditions. This is likely due to inhibition of platelet adhesion and mitigating thromboinflammation at the endothelium in the microvasculature.