Phosphatidylserine is an overlooked mediator of COVID-19 thromboinflammation

A ubiquitous component of cell membrane, phosphatidylserine (PS), is likely to play a major, but as yet unrecognized, role in the thromboinflammation of COVID-19 and other critical illnesses. PS is present in all plasma membranes but is “hidden” on the inner surface by the action of an ATP-requiring enzyme. Failure of PS to be sequestered on the inner surface of cell membranes, release of PS-containing microparticles from cells, or shedding of enveloped viruses allows it to interact with extracellular proteins, including those of the coagulation and complement systems. Detection and quantification of circulating PS is not standardized, and current methodologies have either focused on circulating cellular elements or subcellular plasma components, but not both. PS may also promote thromboinflammation without circulating if expressed on the surface of endothelial cells, a condition that might only be documented if novel imaging techniques are developed. Research into the role of PS in inflammation and coagulation, called here a “procoagulant phospholipidopathy” may provide novel insights and therapeutic approaches for patients with a variety of illnesses.