Antibody-mediated procoagulant platelet formation in COVID-19 is AKT dependent.
J Thromb Haemost
; 20(2): 387-398, 2022 02.
Article
in English
| MEDLINE | ID: covidwho-1506601
ABSTRACT
BACKGROUND:
Thromboembolic 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.OBJECTIVES:
In 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 ANDMETHODS:
Platelets, 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.RESULTS:
Platelets 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.CONCLUSIONS:
Our 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-akt
/
COVID-19
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Thromb Haemost
Journal subject:
Hematology
Year:
2022
Document Type:
Article
Affiliation country:
Jth.15587
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