Elsevier

Thrombosis Research

Volume 223, March 2023, Pages 24-33
Thrombosis Research

Full Length Article
Head-to-head comparison of four COVID-19 vaccines on platelet activation, coagulation and inflammation. The TREASURE study

https://doi.org/10.1016/j.thromres.2023.01.015Get rights and content
Under a Creative Commons license
open access

Abstract

Introduction

Studies exploring alterations in blood coagulation and platelet activation induced by COVID-19 vaccines are not concordant. We aimed to assess the impact of four COVID-19 vaccines on platelet activation, coagulation, and inflammation considering also the immunization dose and the history of SARS-CoV-2 infection.

Methods

TREASURE study enrolled 368 consecutive subjects (161 receiving viral vector vaccines -ChAdOx1-S/Vaxzevria or Janssen- and 207 receiving mRNA vaccines -Comirnaty/Pfizer-BioNTech or Spikevax/Moderna). Blood was collected the day before and 8 ± 2 days after the vaccination. Platelet activation markers (P-selectin, aGPIIbIIIa and Tissue Factor expression; number of platelet-monocyte and -granulocyte aggregates) and microvesicle release were analyzed by flow cytometry. Platelet thrombin generation (TG) capacity was measured using the Calibrated Automated Thrombogram. Plasma coagulation and inflammation markers and immune response were evaluated by ELISA.

Results

Vaccination did not induce platelet activation and microvesicle release. IL-6 and CRP levels (+30%), D-dimer, fibrinogen and F1+2 (+13%, +3.7%, +4.3%, respectively) but not TAT levels significantly increased upon immunization with all four vaccines, with no difference among them and between first and second dose. An overall minor post-vaccination reduction of aPC, TM and TFPI, all possibly related to endothelial function, was observed. No anti-PF4 seroconversion was observed.

Conclusion

This study showed that the four COVID-19 vaccines administered to a large population sample induce a transient inflammatory response, with no onset of platelet activation. The minor changes in clotting activation and endothelial function might be potentially involved at a population level in explaining the very rare venous thromboembolic complications of COVID-19 vaccination.

Abbreviations

VITT
vaccine-induced immune thrombotic thrombocytopenia
COVID-19
Coronavirus disease 2019
TF
Tissue Factor
MVs
microvesicles
aGPIIbIIIa
activated glycoprotein IIbIIIa
AnnV
annexinV
PS
phosphatidylserine
CAT
Calibrated Automated Thrombogram
F1+2
prothrombin fragment 1+2
TAT
Thrombin Anti Thrombin
PT
Prothrombin Time
aPTT
Activated Partial Thromboplastin Clotting Time
aPC
activated Protein C
TM
thrombomodulin
TFPI
Tissue Factor Pathway Inhibitor
PAI-1
Plasminogen Activator Inhibitor-1
vWF
von Willebrand Factor
FVIII:C
Factor VIII clotting activity
IL-6
Interleukin-6
CRP
C-Reactive Protein
PRP
platelet rich plasma
PFP
platelet free plasma

Keywords

COVID-19 vaccine
Coagulation
Inflammation
Platelet activation
Thrombosis
Endothelial dysfunction

Data availability

All data and materials are available from the corresponding authors upon written request.

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1

These authors equally contributed.