• Tatiana von Bahr Greenwood, Bernhard Holzgraefe, Chiang Samuel C C SCC, Yini Wang, Bianca Tesi, Yenan T Bryceson, and Jan-Inge Henter.
• From the Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden (TvBG, YW, BT, J-IH), Section of Paediatric Oncology, Theme of Children's Health, Karolinska University Hospital, Stockholm, Sweden (TvBG, J-IH), Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden (BH), Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden (SCCC, YTB), Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China (YW), Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet (BT) and Karolinska University Laboratory, Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden (BT).
• Eur J Anaesthesiol. 2021 Jul 1; 38 (7): 692-701.

BackgroundSevere pandemic influenza has been associated with the hyperinflammatory condition secondary haemophagocytic lymphohistiocytosis (HLH).ObjectivesTo determine the frequency, degree, character and possible cause of influenza-associated HLH in critically ill patients with severe acute respiratory distress syndrome due to influenza A (H1N1) infection requiring extracorporeal membrane oxygenation (ECMO) support at our hospital.DesignA retrospective observational study.Patients And SettingMedical data were retrieved retrospectively from 11 consenting patients of thirteen adults infected with pandemic influenza A (H1N1) 2009 requiring ECMO between July 2009 and January 2010 at the ECMO Centre of Karolinska University Hospital, Stockholm, Sweden. All patients were evaluated for HLH using HLH-2004 criteria and HScore.ResultsEleven patients (median age 31 years) were included in the study and all survived. All patients showed signs of multiple organ dysfunction and pronounced inflammation, more severe in the four patients with HLH who had significantly higher peak serum concentrations of ferritin (P = 0.024), alkaline phosphatase (P = 0.012) and gamma-glutamyl transferase (P = 0.024), lower concentration of albumin (P = 0.0086) and more frequently hepatomegaly (P = 0.048). Abnormal lymphocyte cytotoxicity (lytic units <10) and a low proportion of natural killer (NK) cells were observed in three of four patients with HLH. Notably, we found a significant inverse correlation between serum ferritin concentration and NK cell and cytotoxic T lymphocyte percentages (rs = -0.74, P = 0.0013 and rs = -0.79, P = 0.0025, respectively). One HLH patient received HLH-directed cytotoxic therapy, another intravenous immunoglobulin and the other two no specific HLH-directed therapy.ConclusionCritically ill patients, including healthy young adults, with pandemic influenza may develop HLH and should be monitored for signs of hyperinflammation and increasing organ dysfunction, and evaluated promptly for HLH because HLH-directed therapy may then be beneficial. The association of low NK percentages with hyperferritinaemia may suggest a role for reduced NK cell numbers, possibly also cytotoxic T lymphocytes, and subsequently reduced lymphocyte cytotoxicity, in the pathogenesis of hyperinflammation and secondary HLH.Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology.

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