title: Patients with an extraordinarily elevated serum ferritin: think of haemophagocytic lymphohistiocytosis.
abstract: BACKGROUND
  We retrospectively analysed charts of patients with blood ferritin level >5000 µg/l. The aim of the study was to look for the likelihood of haemophagocytic lymphohistiocytosis (HLH) in these patients.
  
  
  METHODS
  Forty-two patients demonstrated hyperferritinaemia and could be evaluated. The diagnosis of HLH was based on a recently published HScore and an earlier diagnostic algorithm.
  
  
  RESULTS
  According to the algorithm, 20 patients fulfilled the criteria for a diagnosis of HLH. However, patients with Still's disease have macrophage activation and, in this context, a rise in ferritin without having HLH. Fourteen patients with carcinoma, haematological malignancies or infection and hyperferritinaemia remained. Signs and symptoms were: systemic inflammatory response syndrome (SIRS 100%), fever (95%), cytopenia of ≥2 lines (70%), immunosuppression (61.5%), splenomegaly (50%), elevated liver enzymes (45%), lymphadenopathy (35%), hepatomegaly (30%). These are nonspecific parameters. Therefore HLH may be overdiagnosed. Using the HScore, only 10 patients had >80% probability of having HLH. Patients demonstrating cytopenia of ≥2 cell lines had a >60% mortality rate. Time to death was 13.8 days; death was most often due to multiorgan failure.
  
  
  CONCLUSIONS
  HScore reflects a higher specificity than the algorithm for diagnosing HLH. The discrepancy may indicate the difficulty that a specific marker still is missing. Hyperferritinaemia was strongly associated with HLH in patients with haematological or oncological malignancies. HLH may be underdiagnosed because the majority of these patients suffer from a severe underlying disease, which easily might suggest a flare or infection. In this population, hyperferritinaemia and SIRS should rise suspicion because mortality in HLH is high.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University of Tübingen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schweizer
authors.affiliation: Division of Haematology, University Hospital of Zurich, Switzerland.
authors.forename: Jeroen S
authors.initials: JS
authors.lastname: Goede
authors.affiliation: Department of Medicine, Cantonal Hospital of Lucerne, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Briner
mesh_terms: D000368:Aged; D000465:Algorithms; D015415:Biomarkers; D003937:Diagnosis, Differential; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D005293:Ferritins