Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients (HEMICU): a prospective observational study protocol
Claudia Spies,
Gunnar Lachmann,
Cornelia Knaak,
Clarissa von Haefen,
Nadine Paeschke,
Christian Meisel,
Peter Nyvlt,
Friederike S Schuster,
Sophie K Piper,
Jochen Kruppa,
Gerald Vorderwülbecke,
Felix Balzer,
Paul La Rosée,
Thomas Schenk,
Nadine Unterwalder,
Uwe Kölsch,
Nils Lachmann,
Levent Akyüz,
Frank M Brunkhorst,
Hans-Dieter Volk,
Didier Keh
Affiliations
Claudia Spies
Department of Anesthesiology and Operative Intensive Care Medicine, Campus Virchow Klinikum and Charité Centrum Mitte (CVK/CCM), Charité Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin, Institute of Health, Berlin, Germany
Gunnar Lachmann
Department of Anesthesiology and Operative Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
Cornelia Knaak
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Clarissa von Haefen
Department of Anesthesiology and Operative Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
Nadine Paeschke
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Christian Meisel
6Berlin, Department of Immunology, Labor Berlin GmbH, Berlin, Germany
Peter Nyvlt
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Friederike S Schuster
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Sophie K Piper
Institute of Biometry and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Jochen Kruppa
Institute of Biometry and Clinical Epidemiology, Charité Universitätsmedizin Berlin, Berlin, Germany
Gerald Vorderwülbecke
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Felix Balzer
Institute of Medical Informatics, Charité Universitätsmedizin Berlin, Berlin, Germany
Paul La Rosée
Klinik für Innere Medizin II, Schwarzwald-Baar Klinikum, Villingen-Schwenningen, Germany
Thomas Schenk
Department of Hematology and Oncology, Universitätsklinikum Jena, Jena, Germany
Nadine Unterwalder
8Labor Berlin, Berlin, Germany
Uwe Kölsch
Department of Immunology, Labor Berlin - Charité Vivantes GmbH, Berlin, Germany
Nils Lachmann
Institute for Transfusion Medicine, H&I Laboratory, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Levent Akyüz
Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Frank M Brunkhorst
1 Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany
Hans-Dieter Volk
Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Didier Keh
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Introduction Haemophagocytic lymphohistiocytosis (HLH) in adults is characterised by toxic immune activation and a sepsis-like syndrome, leading to high numbers of undiagnosed cases and mortality rates of up to 68%. Early diagnosis and specific immune suppressive treatment are mandatory to avoid fatal outcome, but the diagnostic criteria (HLH-2004) are adopted from paediatric HLH and have not been validated in adults. Experimental studies suggest biomarkers to sufficiently diagnose HLH. However, biomarkers for the diagnosis of adult HLH have not yet been investigated.Methods and analysis The HEMICU (Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients) study aims to estimate the incidence rate of adult HLH among suspected adult patients in intensive care units (ICUs). Screening for HLH will be performed in 16 ICUs of Charité – Universitätsmedizin Berlin. The inclusion criteria are bicytopaenia, hyperferritinaemia (≥500 µg/L), fever or when HLH is suspected by the clinician. Over a period of 2 years, we expect inclusion of about 100 patients with suspected HLH. HLH will be diagnosed if at least five of the HLH-2004 criteria are fulfilled, together with an expert review; all other included patients will serve as controls. Second, a panel of potential biomarker candidates will be explored. DNA, plasma and serum will be stored in a biobank. The primary endpoint of the study is the incidence rate of adult HLH among suspected adult patients during ICU stay. Out of a variety of measured biomarkers, this study furthermore aims to find highly potential biomarkers for the diagnosis of adult HLH in ICU. The results of this study will contribute to improved recognition and patient outcome of adult HLH in clinical routine.Ethics and dissemination The institutional ethics committee approved this study on 1 August 2018 (Ethics Committee of Charité – Universitätsmedizin Berlin, EA4/006/18). The results of the study will be disseminated in an international peer-reviewed journal and presented at international conferences.Trial registration number NCT03510650.
