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Antibody-mediated procoagulant platelet formation in COVID-19 is AKT dependent.
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.
  • Pelzl L; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Singh A; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Funk J; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Witzemann A; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Marini I; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Zlamal J; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Weich K; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Abou-Khalel W; Centre for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany.
  • Hammer S; Centre for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany.
  • Uzun G; Centre for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany.
  • Althaus K; Centre for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany.
  • Bakchoul T; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
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 AND

METHODS:

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.
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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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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