{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:20:41Z","timestamp":1780597241859,"version":"3.54.1"},"reference-count":30,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Hungarian National Research, Development And Innovation Office","award":["K138816"],"award-info":[{"award-number":["K138816"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,10,18]]},"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro\n                      <jats:sup>\u00ae<\/jats:sup>\n                      device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T\n                      <jats:sub>0<\/jats:sub>\n                      ) then after 24, 48 hours, then on day 5 and 7 (T\n                      <jats:sub>1-4<\/jats:sub>\n                      , respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval was given by the Medical Research Council of Hungary (1405-3\/2022\/E\u00dcG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05218369\">NCT05218369<\/jats:ext-link>\n                      ; Clinicaltrials.gov.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-063856","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T11:42:57Z","timestamp":1667562177000},"page":"e063856","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Investigating the association between IL-6 antagonist therapy and blood coagulation in critically ill patients with COVID-19: a protocol for a prospective, observational, multicentre study"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct05218369","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-2296","authenticated-orcid":false,"given":"Em\u0151ke Henrietta","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University, Budapest, Hungary"},{"name":"Selye J\u00e1nos Doctoral College for Advanced Studies, Semmelweis University, Budapest, Hungary"},{"name":"Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1t\u00e9","family":"Rottler","sequence":"additional","affiliation":[{"name":"Szent Gy\u00f6rgy University Teaching Hospital of Fej\u00e9r County, Sz\u00e9kesfeh\u00e9rv\u00e1r, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanni","family":"Dembrovszky","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University, Budapest, Hungary"},{"name":"Institute for Translational Medicine, Medical School, University of P\u00e9cs, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-2506","authenticated-orcid":false,"given":"Klementina","family":"Ocskay","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University, Budapest, Hungary"},{"name":"Institute for Translational Medicine, Medical School, University of P\u00e9cs, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University, Budapest, Hungary"},{"name":"Institute for Translational Medicine, Medical School, University of P\u00e9cs, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-7259","authenticated-orcid":false,"given":"P\u00e9ter","family":"Hegyi","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University, Budapest, Hungary"},{"name":"Institute for Translational Medicine, Medical School, University of P\u00e9cs, P\u00e9cs, Hungary"},{"name":"Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1468-4058","authenticated-orcid":false,"given":"Zsolt","family":"Moln\u00e1r","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University, Budapest, Hungary"},{"name":"Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary"},{"name":"Department of Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n","family":"T\u00e1nczos","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary"},{"name":"Soproni Erzs\u00e9bet Teaching Hospital and Rehabilitation Institute, Sopron, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"2025121406552060000_12.11.e063856.1","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1016\/S2213-2600(20)30216-2","article-title":"COVID-19 cytokine storm: the interplay between inflammation and coagulation","volume":"8","author":"Jose","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2025121406552060000_12.11.e063856.2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14869"},{"key":"2025121406552060000_12.11.e063856.3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/ijlh.13500","article-title":"COVID-19: thrombosis, thromboinflammation, and anticoagulation considerations","volume":"43 Suppl 1","author":"Levy","year":"2021","journal-title":"Int J Lab Hematol"},{"key":"2025121406552060000_12.11.e063856.4","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.1182\/bloodadvances.2022007561","article-title":"American society of hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: January 2022 update on the use of therapeutic-intensity anticoagulation in acutely ill patients","volume":"6","author":"Cuker","year":"2022","journal-title":"Blood Adv"},{"key":"2025121406552060000_12.11.e063856.5","unstructured":"National Iinstitute of Health COVID-19 Treatment Guidelines . Antithrombotic therapy in patients with COVID-19, 2022. Available: https:\/\/www.covid19treatmentguidelines.nih.gov\/therapies\/antithrombotic-therapy\/ [Accessed 23 Aug 2022]."},{"key":"2025121406552060000_12.11.e063856.6","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0338"},{"key":"2025121406552060000_12.11.e063856.7","doi-asserted-by":"publisher","DOI":"10.2174\/157340308785160570"},{"key":"2025121406552060000_12.11.e063856.8","doi-asserted-by":"crossref","unstructured":"Bester J , Pretorius E . Effects of IL-1\u03b2, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci Rep 2016;6.doi:10.1038\/srep32188","DOI":"10.1038\/srep32188"},{"key":"2025121406552060000_12.11.e063856.9","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1021\/acs.jproteome.0c00365","article-title":"Serum proteomics in COVID-19 patients: altered coagulation and complement status as a function of IL-6 level","volume":"19","author":"D'Alessandro","year":"2020","journal-title":"J Proteome Res"},{"key":"2025121406552060000_12.11.e063856.10","unstructured":"COVID-19 Treatment Guidelines Panel . Coronavirus disease 2019 (COVID-19) treatment guidelines National Institutes of Health; 2022. https:\/\/www.covid19treatmentguidelines.nih.gov\/ [Accessed 18 Aug 2022]."},{"key":"2025121406552060000_12.11.e063856.11","unstructured":"World Health Organization . Therapeutics and COVID-19: living guideline; 2021. WHO\/2019-nCoV\/therapeutics\/2021.2 [Accessed 6 July 2021]."},{"key":"2025121406552060000_12.11.e063856.12","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.050051"},{"key":"2025121406552060000_12.11.e063856.13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.5770\/cgj.23.463","article-title":"Using the clinical frailty scale in allocating scarce health care resources","volume":"23","author":"Rockwood","year":"2020","journal-title":"Can Geriatr J"},{"key":"2025121406552060000_12.11.e063856.14","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.bja.2020.12.010","article-title":"Impaired fibrinolysis in critically ill COVID-19 patients","volume":"126","author":"Bachler","year":"2021","journal-title":"Br J Anaesth"},{"key":"2025121406552060000_12.11.e063856.15","unstructured":"Hungarian Ministry of Human Resources (Emberi Er\u0151forr\u00e1sok Miniszt\u00e9riuma) . Basics of the treatment of confirmed COVID-19 infected adults (Igazolt COVID-19 fert\u0151z\u00f6tt feln\u0151ttek kezel\u00e9s\u00e9nek alapjai). In: Handbook for the prevention and treatment of new coronavirus (SARS-CoV-2) infections (COVID-19) identified in 2020 a 2020. \u00c9vben azonos\u00edtott \u00faj koronav\u00edrus (SARS-CoV-2) okozta fert\u0151z\u00e9sek (COVID-19) megel\u0151z\u00e9s\u00e9nek \u00e9s ter\u00e1pi\u00e1j\u00e1nak k\u00e9zik\u00f6nyve) (IV\/10948-8\/2020\/EGPOL), 2022. https:\/\/koronavirus.gov.hu\/sites\/default\/files\/sites\/default\/files\/imce\/magyar_koronavirus_kezikonyv_igazolt_covid-19_betegek_kezelese_cimu_fejezet_-_2021_november.pdf"},{"key":"2025121406552060000_12.11.e063856.16","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.07.045120"},{"key":"2025121406552060000_12.11.e063856.17","doi-asserted-by":"crossref","DOI":"10.1016\/j.micpath.2021.104799","article-title":"The pro-inflammatory cytokines in COVID-19 pathogenesis: what goes wrong?","volume":"153","author":"Darif","year":"2021","journal-title":"Microb Pathog"},{"key":"2025121406552060000_12.11.e063856.18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.pulmoe.2020.07.003","article-title":"Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review","volume":"27","author":"Cortegiani","year":"2021","journal-title":"Pulmonology"},{"key":"2025121406552060000_12.11.e063856.19","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14768"},{"key":"2025121406552060000_12.11.e063856.20","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3390\/jcm10020191","article-title":"Proposal of the definition for covid-19-associated coagulopathy","volume":"10","author":"Iba","year":"2021","journal-title":"J Clin Med"},{"key":"2025121406552060000_12.11.e063856.21","doi-asserted-by":"crossref","DOI":"10.3390\/jcm10081740","article-title":"Viscoelastometric testing to assess hemostasis of COVID-19: a systematic review","volume":"10","author":"Bareille","year":"2021","journal-title":"J Clin Med"},{"key":"2025121406552060000_12.11.e063856.22","doi-asserted-by":"crossref","first-page":"S299","DOI":"10.21037\/jtd.2017.03.85","article-title":"Viscoelastic testing inside and beyond the operating room","volume":"9","author":"Shen","year":"2017","journal-title":"J Thorac Dis"},{"key":"2025121406552060000_12.11.e063856.23","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01093"},{"key":"2025121406552060000_12.11.e063856.24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100433"},{"key":"2025121406552060000_12.11.e063856.25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s40744-018-0102-x","article-title":"A review of recent advances using tocilizumab in the treatment of rheumatic diseases","volume":"5","author":"Rubbert-Roth","year":"2018","journal-title":"Rheumatol Ther"},{"key":"2025121406552060000_12.11.e063856.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.10.036"},{"key":"2025121406552060000_12.11.e063856.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00676-0"},{"key":"2025121406552060000_12.11.e063856.28","doi-asserted-by":"crossref","unstructured":"Ortega-Paz L , Galli M , Capodanno D . Safety and efficacy of different prophylactic anticoagulation dosing regimens in critically and non-critically ill patients with covid-19: a systematic review and meta-analysis of randomized controlled trials. Eur Heart J Cardiovasc Pharmacother 2021.doi:10.1093\/ehjcvp\/pvab070","DOI":"10.1093\/ehjcvp\/pvac010"},{"key":"2025121406552060000_12.11.e063856.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2020.12.073"},{"key":"2025121406552060000_12.11.e063856.30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ajem.2021.01.016","article-title":"Effect of antiplatelet treatments on patients with COVID-19 infection: a systematic review and meta-analysis","volume":"43","author":"Wang","year":"2021","journal-title":"Am J Emerg Med"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2022-063856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T14:55:32Z","timestamp":1765724132000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2022-063856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11,4]]},"published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1136\/bmjopen-2022-063856"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2022-063856","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11]]}}}