Longitudinal multiparametric characterization of platelet dysfunction in COVID-19: Effects of disease severity, anticoagulation therapy and inflammatory status

Autor: Alexey A. Martyanov, Anna E. Boldova, Maria G. Stepanyan, Olga I. An, Alexander S. Gur'ev, Darya V. Kassina, Alexey Y. Volkov, Alexandr V. Balatskiy, Andrei A. Butylin, Sergei S. Karamzin, Elena V. Filimonova, Sergei V. Tsarenko, Sergei A. Roumiantsev, Alexander G. Rumyantsev, Mikhail A. Panteleev, Fazoil I. Ataullakhanov, Anastasia N. Sveshnikova
Rok vydání: 2021
Předmět:
Blood Platelets
ECMO
Extracorporeal Membrane Oxygenation
VWF
Von Willebrand Factor
Severity of Illness Index
Article
ICU
Intensive Care Unit
MFI
Mean Fluorescence Intensity
TPO
Thrombopoietin
Humans
IL
Interleukin
NET
Neutrophil Extracellular TRAP
PCR
Polymerase Chain Reaction
Flow cytometry
LMWH
Low Molecular Weight Heparin
COVID-19
Coronavirus disease 2019
PPP
Platelet Poor Plasma
SARS-CoV-2
Anticoagulants
COVID-19
ARDS
Acute Respiratory Distress Syndrome
Thrombosis
Hematology
Extracellular traps
Heparin
Low-Molecular-Weight
GPIb
Glycoprotein Ib
TRAP
Thrombin Receptor Activating Peptide
LPS
Lipopolysaccharides
Thrombocytopenia
PAR
Protease Activated Receptor
COVID-19 Drug Treatment
ACE-2
Angiotensin Converting Enzyme 2
PRP
Platelet Rich Plasma
GPVI
Glycoprotein VI
ADAM-17
A Disintegrin and Metalloprotease 17
RNA
Viral
PMA
Phorbol Myristate Acetate
CLEC-2
C-type lectin-like receptor 2
BSA
Bovine Serum Albumin
MAPK
Mitogen-activated Protein Kinase
FSC
Forward Light Scattering
Zdroj: Thrombosis Research
ISSN: 1879-2472
Popis: Introduction Defects of platelet functional responses in COVID-19 were reported, but their origin and pathophysiological significance are unclear. The objective of this study was to characterize the thrombocytopathy in COVID-19. Materials and methods Analysis of platelet functional responses to activation by flow cytometry and aggregometry in 46 patients with confirmed COVID-19 of different severity (non-ICU, ICU, and ECMO) over the course of hospitalization alongside with plasma coagulation, inflammatory markers (CRP, fibrinogen, NETosis assays in smears) was performed. Results and conclusions All patients had increased baseline percentage of procoagulant platelets (healthy: 0.9 ± 0.5%; COVID-19: 1.7 ± 0.6%). Patients had decreased agonist-induced platelet GPIb shedding (1.8 ± 0.7 vs 1.25 ± 0.4), P-Selectin exposure (1.51 ± 0.21 vs 1.1 ± 0.3) and aggregation. The values of these parameters among the non-ICU and ICU cohorts differed modestly, while the ECMO cohort differed significantly. Only ECMO patients had pronounced thrombocytopenia. While inflammatory markers improved over time, the observed platelet functional responses changed only moderately. SARS-CoV-2 RNA was found in 8% of blood samples and it did not correlate with platelet counts or responses. All patients had increased NETosis that moderately correlated with platelet dysfunction. High cumulative dosages of LMWH (average > 12,000 IU/day over 5 days) resulted in an improvement in platelet parameters. The observed pattern of platelet refractoriness was reproduced by in vitro pre-treatment of washed platelets with subnanomolar thrombin or perfusion of blood through a collagen-covered flow chamber. We conclude that platelet dysfunction in COVID-19 is consistent with the intravascular-coagulation-induced refractoriness rather than with an inflammation-induced mechanism or a direct activation by the virus.
Databáze: OpenAIRE
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