Antibody-mediated procoagulant platelet formation in COVID-19 is AKT dependent.

Content Provider	Europe PMC
Author	Pelzl, Lisann Singh, Anurag Funk, Jonas Witzemann, Andreas Marini, Irene Zlamal, Jan Weich, Karoline Abou‐Khalel, Wissam Hammer, Stefanie Uzun, Guenalp Althaus, Karina Bakchoul, Tamam
Copyright Year	2021
Abstract	BackgroundThromboembolic events are frequently reported in patients infected with the SARS‐CoV‐2. Recently, we observed that platelets from patients with severe COVID‐19 infection express procoagulant phenotype. The molecular mechanisms that induce the generation of procoagulant platelets in COVID‐19 patients are not completely understood.ObjectivesIn this study, we investigated the role of AKT (also known as Protein Kinase B), which is the major downstream effector of PI3K (phosphoinositid‐3‐kinase) (PI3K/AKT) signaling pathway in platelets from patients with COVID‐19.Patients and MethodsPlatelets, Sera and IgG from COVID‐19 patients who were admitted to the intensive care unit (ICU) were analyzed by flow cytometry as well as western blot and adhesion assays.ResultsPlatelets from COVID‐19 patients showed significantly higher levels of phosphorylated AKT, which was correlated with CD62p expression and phosphatidylserine (PS) externalization. In addition, healthy platelets incubated with sera or IgGs from ICU COVID‐19 patients induced phosphorylation of PI3K and AKT and were dependent on Fc‐gamma‐RIIA (FcγRIIA). In contrast, ICU COVID‐19 sera mediated generation of procoagulant platelets was not dependent on GPIIb/IIIa. Interestingly, the inhibition of phosphorylation of both proteins AKT and PI3K prevented the generation of procoagulant platelets.ConclusionsOur study shows that pAKT/AKT signaling pathway is associated with the formation of procoagulant platelets in severe COVID‐19 patients without integrin GPIIb/IIIa engagement. The inhibition of PI3K/AKT phosphorylation might represent a promising strategy to reduce the risk for thrombosis in patients with severe COVID‐19.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8646637&blobtype=pdf
ISSN	15387933
Journal	Journal of Thrombosis and Haemostasis [J Thromb Haemost]
Volume Number	20
DOI	10.1111/jth.15587
PubMed Central reference number	PMC8646637
Issue Number	2
PubMed reference number	34752677
e-ISSN	15387836
Language	English
Publisher	The Authors. Journal of Thrombosis and Haemostasis published by ELSEVIER INC. on behalf of International Society on Thrombosis and Haemostasis
Publisher Date	2021-12-03
Access Restriction	Open
Rights License	Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. © 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.
Subject Keyword	AKT‐signaling COVID‐19 platelet adhesion procoagulant platelet formation thrombosis
Content Type	Text
Resource Type	Article
Subject	Hematology