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Interleukin-6 receptor blockade with subcutaneous tocilizumab improves coagulation activity in patients with COVID-19.
Di Nisio, Marcello; Potere, Nicola; Candeloro, Matteo; Spacone, Antonella; Pieramati, Leonardo; Ferrandu, Giovanna; Rizzo, Giulia; La Vella, Matteo; Di Carlo, Silvio; Cibelli, Donatella; Parruti, Giustino; Levi, Marcel; Porreca, Ettore.
  • Di Nisio M; Department of Medicine and Ageing Sciences, University G. D'Annunzio, Chieti-Pescara, Italy; Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: mdinisio@unich.it.
  • Potere N; Department of Internal Medicine, "G. D'Annunzio" University, Chieti, Italy.
  • Candeloro M; Department of Medicine and Ageing Sciences, University G. D'Annunzio, Chieti-Pescara, Italy.
  • Spacone A; Respiratory Medicine Unit, Pescara General Hospital, Pescara, Italy.
  • Pieramati L; Department of Internal Medicine, "G. D'Annunzio" University, Chieti, Italy. Electronic address: leonardo.pieramati@tiscali.it.
  • Ferrandu G; Internal Medicine Unit, Pescara General Hospital, Pescara, Italy. Electronic address: giovanna.ferrandu@ausl.pe.it.
  • Rizzo G; Department of Internal Medicine, "G. D'Annunzio" University, Chieti, Italy.
  • La Vella M; Department of Internal Medicine, "G. D'Annunzio" University, Chieti, Italy.
  • Di Carlo S; Geriatric Medicine Unit, Pescara General Hospital, Pescara, Italy. Electronic address: silvio.dicarlo@ausl.pe.it.
  • Cibelli D; Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy. Electronic address: donatellaconcetta.cibelli@ausl.pe.it.
  • Parruti G; Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy.
  • Levi M; Cardiometabolic Programme, National Institute for Health Research University College London Hospitals (UCLH) Biomedical Research Centre, Department of Medicine, UCLH National Health Service Foundation Trust, London NW1 2PG, UK. Electronic address: marcel.levi@nhs.net.
  • Porreca E; Department of Medical, Oral and Biotechnological Sciences, "G. D'Annunzio" University, Chieti, Italy. Electronic address: eporreca@unich.it.
Eur J Intern Med ; 83: 34-38, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065032
ABSTRACT

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Blood Coagulation / Receptors, Interleukin-6 / Antibodies, Monoclonal, Humanized / COVID-19 / COVID-19 Drug Treatment Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Eur J Intern Med Journal subject: Internal Medicine Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Blood Coagulation / Receptors, Interleukin-6 / Antibodies, Monoclonal, Humanized / COVID-19 / COVID-19 Drug Treatment Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Eur J Intern Med Journal subject: Internal Medicine Year: 2021 Document Type: Article