PB0601 - Identification of a novel growth factor-enriched platelet subpopulation: Potential implications for COVID-19

Background: While previous research into platelet subpopulations has focused primarily on platelet reactivity, little is known about platelet subpopulations in the context of granule and growth factor content. Recent studies revealed that platelets contain various numbers of α-granules. Therefore, each platelet contains different levels of stored bioactive substances that mediate platelet function in various physiological and pathophysiological processes. Some of the main complications of COVID-19 are microthrombosis and pulmonary edema due to increased vascular permeability. Vascular endothelial growth factor (VEGF), largely stored in platelet α-granules, plays a central role in promoting vascular permeability.

Aims: To characterize a novel growth factor/α-granule-enriched platelet subpopulation and investigate whether changes in this subpopulation occur under inflammatory conditions with COVID-19 as an example. To identify a potential mechanism by which this growth factor-enriched platelet subpopulation may arise.

Methods: Platelets were isolated from healthy individuals and age- and sex-matched COVID-19-ICU patients and COVID-19-negative controls. Platelets were intracellularly stained for CD62P, VEGF and PDGF. Plasma TNF-α was evaluated using ELISA. The VEGF expression in TNF-α-treated Meg-01 was assessed using flow cytometry.

Results: α-Granule-enriched platelet subpopulations (2.5-5.1%), marked by CD62P, exist with high levels of VEGF and PDGF in healthy donors. Additionally, COVID-19 patients’ platelets demonstrated a higher overall mean in VEGF content and a greater percentage of VEGF-enriched platelet subpopulations compared to COVID-19-negative controls. COVID-19 patients demonstrated higher TNF-α plasma concentrations than COVID-19-negative controls. Treatment of Meg-01 cells with TNF-α led to the formation of a distinct subpopulation with higher intracellular VEGF levels (19.8±1.7%)

Conclusion(s): Preliminary data suggest the existence of a novel α-granule-enriched platelet subpopulation with higher VEGF and PDGF content. Significant alteration of VEGF-enriched platelets subpopulation was observed in COVID-19. This change may be due to the upregulation of TNF-α and subsequent induction of VEGF expression in megakaryocytes; predisposing COVID-19 patients to higher vascular permeability and pulmonary edema upon thrombosis.