Interleukin-6 receptor blockade with subcutaneous tocilizumab improves coagulation activity in patients with COVID-19.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Blood Cell Count
Blood Coagulation
/ physiology
Blood Coagulation Tests
C-Reactive Protein
COVID-19
/ blood
Cohort Studies
Combined Modality Therapy
Female
Hospitalization
Humans
Injections, Subcutaneous
Italy
Male
Middle Aged
Receptors, Interleukin-6
/ antagonists & inhibitors
COVID-19 Drug Treatment
Blood coagulation
COVID-19
Prophylaxis
Thrombosis
Tocilizumab
Journal
European journal of internal medicine
ISSN: 1879-0828
Titre abrégé: Eur J Intern Med
Pays: Netherlands
ID NLM: 9003220
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
29
07
2020
revised:
16
09
2020
accepted:
25
10
2020
pubmed:
10
11
2020
medline:
16
1
2021
entrez:
9
11
2020
Statut:
ppublish
Résumé
Many COVID-19 patients develop a hyperinflammatory response which activates blood coagulation and may contribute to the occurrence of thromboembolic complications. Blockade of interleukin-6, a key cytokine in COVID-19 pathogenesis, may improve the hypercoagulable state induced by inflammation. The aim of this study was to evaluate the effects of subcutaneous tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 receptor on coagulation parameters. Hospitalized adult patients with laboratory-confirmed moderate to critical COVID-19 pneumonia and hyperinflammation, who received a single 324 mg subcutaneous dose of tocilizumab on top of standard of care were enrolled in this analysis. Coagulation parameters were measured before tocilizumab and at day 1, 3, and 7 after treatment. All patients were followed-up for 35 days after admission or until death. 70 patients (mean age 60 years, interquartile range 52-75) were included. Treatment with tocilizumab was associated with a reduction in D-dimer levels (-56%; 95% confidence interval [CI], -68% to -44%), fibrinogen (-48%; 95%CI, -60% to -35%), C-reactive protein (-93%; 95%CI, -99% to -87%), prothrombin time (-4%; 95%CI,-9% to 0.8%), and activated thromboplastin time (-4%; 95%CI,-8.7% to 0.8%), and an increase in platelet count (34%; 95%CI, 23% to 45%). These changes occurred already one day after treatment with sustained reductions throughout day 7. The improvement in coagulation was consistently observed in patients receiving prophylactic or therapeutic dose anticoagulants, and was paralleled by a rapid improvement in respiratory function. Subcutaneous tocilizumab was associated with significant improvement of blood coagulation parameters independently of thromboprophylaxis dose.
Sections du résumé
BACKGROUND
Many COVID-19 patients develop a hyperinflammatory response which activates blood coagulation and may contribute to the occurrence of thromboembolic complications. Blockade of interleukin-6, a key cytokine in COVID-19 pathogenesis, may improve the hypercoagulable state induced by inflammation. The aim of this study was to evaluate the effects of subcutaneous tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 receptor on coagulation parameters.
METHODS
Hospitalized adult patients with laboratory-confirmed moderate to critical COVID-19 pneumonia and hyperinflammation, who received a single 324 mg subcutaneous dose of tocilizumab on top of standard of care were enrolled in this analysis. Coagulation parameters were measured before tocilizumab and at day 1, 3, and 7 after treatment. All patients were followed-up for 35 days after admission or until death.
RESULTS
70 patients (mean age 60 years, interquartile range 52-75) were included. Treatment with tocilizumab was associated with a reduction in D-dimer levels (-56%; 95% confidence interval [CI], -68% to -44%), fibrinogen (-48%; 95%CI, -60% to -35%), C-reactive protein (-93%; 95%CI, -99% to -87%), prothrombin time (-4%; 95%CI,-9% to 0.8%), and activated thromboplastin time (-4%; 95%CI,-8.7% to 0.8%), and an increase in platelet count (34%; 95%CI, 23% to 45%). These changes occurred already one day after treatment with sustained reductions throughout day 7. The improvement in coagulation was consistently observed in patients receiving prophylactic or therapeutic dose anticoagulants, and was paralleled by a rapid improvement in respiratory function.
CONCLUSIONS
Subcutaneous tocilizumab was associated with significant improvement of blood coagulation parameters independently of thromboprophylaxis dose.
Identifiants
pubmed: 33162299
pii: S0953-6205(20)30406-4
doi: 10.1016/j.ejim.2020.10.020
pmc: PMC7608031
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Receptors, Interleukin-6
0
C-Reactive Protein
9007-41-4
tocilizumab
I031V2H011
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
34-38Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
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