Red cell extracellular vesicles and coagulation activation pathways.

Abstract

Packed red blood cells (PRBCs) are the most commonly transfused blood products. Preparation of PRBCs requires blood collection from donors, processing, and storage prior to transfusion to recipients. Stored red blood cells (RBCs) undergo structural and metabolic changes collectively known as the storage lesion. RBC extracellular vesicles (sREVs) are released in PRBC units during storage, and are transfused along with intact RBCs into recipients. For several decades, extracellular vesicles have been the focus of intense research, leading to the discovery of a wide variety of endogenous biological properties that may impact numerous physiologic and/or pathologic pathways. This study reviews the characteristics of extracellular vesicles present in PRBC units and the impact of prestorage and pretransfusion processing, as well as storage conditions, on their generation. Importantly, we discuss recently described interactions of sREVs with coagulation pathways and related interplay with inflammatory pathways in vitro and in vivo using animal models. Extracellular vesicles present in stored PRBC units are capable of activating coagulation pathways. However, it remains unclear whether this affects clinical outcomes in recipients of PRBC units. Further understanding of these pathways and their relationship to any adverse outcomes may yield novel strategies to mitigate complications of blood transfusion.