Desialylation of platelet surface glycans enhances platelet adhesion to adsorbent polymers for lipoprotein apheresis

Abstract

Background: Lipoprotein apheresis is an important therapeutic option in homozygous familial hypercholesterolemia, progressive atherosclerosis, or when depletion of lipoprotein(a) is indicated. It is generally regarded as safe, but drops in platelet counts as well as sporadic episodes of thrombocytopenia have been reported. We assessed the influence of platelet desialylation, which may be induced by endogenous or pathogen-derived neuraminidases, on platelet adhesion to polyacrylate-based adsorbents for whole blood lipoprotein apheresis. Methods: Medical grade platelet concentrates were incubated with neuraminidase in vitro and were circulated over adsorbent columns downscaled from clinical application. Results: Cleavage of terminal sialic residues resulted in platelet activation with significantly elevated expression of platelet factor 4 (PF4) and in enhanced platelet adhesion to the adsorbent, accompanied by a pronounced drop in platelet counts in the column flow-through. Conclusion: Alterations in endogenous neuraminidase activity or exogenous (pathogen-derived) neuraminidase may trigger enhanced platelet adhesion in whole blood lipoprotein apheresis.

Possible Role of P-selectin Adhesion in Long-COVID: A Comparative Analysis of a Long-COVID Case Versus an Asymptomatic Post-COVID Case

“…SiA receptor-destroying enzymes like Neuraminidase (NEU) in influenza or hemagglutinin-esterase (HE) in some coronaviruses, mediate cleavage of surface SiA-containing cell receptors promoting viral particles release from infected cells. Endogenous cell NA activity plays a role in shedding of cell surface SiA, plays a key role in activation of both platelets [50] and neutrophils [51]. While SARS-CoV-2 seem to be lacking HE gene [52], samples from COVID-19 patients revealed an overexpression of NEU in infected neutrophils and treatment with NEU inhibitors led to decreased host NEU-mediated shedding of cell SiA and reduced overactivation of neutrophils [53].…”

Polyzwitterionic Coating of Porous Adsorbents for Therapeutic Apheresis

“…Blood compatibility is particularly important in therapeutic hemapheresis, where adsorbent polymers are in direct contact with whole blood. We have previously characterized the relationship between the physicochemical characteristics of adsorbent polymers used for hemapheresis and cellular activation at the blood–biomaterial interface [ 9 , 10 , 11 , 12 , 13 ]. Here, we aimed to develop blood-compatible zwitterionic polymers that can be applied as surface coatings to enhance the blood compatibility of porous adsorbents.…”