Extreme hyperferritinaemia: further considerations

Abstract

Extreme hyperferritinaemia: further considerationsIn their case report, Sami et al. 1 state that very high ferritin concentrations (greater than 10,000 mg/L) have only been described in adult Still's disease, multiple blood transfusions and severe acute hepatocellular damage. It may be of interest to the authors that such marked hyperferritinaemia has also been documented in patients with the human immunodeficiency virus (HIV) complicated by superinfection with a range of opportunistic organisms, particularly disseminated histoplasmosis. 2 We would also like to emphasize that haemophagocytic syndromes, such as haemophagocytic lymphohistiocytosis (HLH), may also produce ferritin concentrations of this magnitude. 3,4 A variety of drugs, infections and rheumatological diseases, including but not exclusively adult Still's disease, may precipitate a haemophagocytic process, 5 or it may be a primary disorder. The diagnosis of HLH relies on the patient satisfying sufficient criteria, of which serum ferritin is a part. 6 As an aside, it appears that haemophagocytosis is associated with lower glycosylation of circulating ferritin, 7 a feature that may extend to other circulation proteins, notably transferrin, 8 possibly due to liver involvement by the pathological process. As an illustrative example, a recent case from our laboratory of a five-year-old girl with HLH secondary to Epstein-Barr virus (EBV) infection demonstrated a serum ferritin concentration of 29,600 mg/L at diagnosis and detectable serum asialotransferrin on isoelectric focusing.A review of all ferritin results greater than 10,000 mg/L from our laboratory network in the past year found 35 results from 30 patients (0.06% of all ferritin requests). Most patients had received multiple transfusions for a variety of reasons (14 cases) or had severe acute hepatocellular damage (9 cases); however, there were four cases of HLH: two adult, both fatal, and two paediatric, both secondary to EBV infection. Three cases of high ferritin were not clearly explained.

Hyperferritinemia: causes and significance in a general hospital

“…Most of the previous studies either defined primary diagnosis as a single cause or allowed multiple diseases as causes of hyperferritinemia [8][9][10][11][13][14][15][16]. Our observation that 41% of the patients with hyperferritinemia had multiple underlying causes indicated that, together with reports showing that 16.8-46% of patients with hyperferritinemia had more than one etiology, either approach was not satisfactory to elucidate the etiologies of hyperferritinemia encountered in the clinical setting [8,13,17].…”

“…As the range of the serum ferritin level is wide without upper limit but the ferritin elevation was mild or modest in many patients, it appeared clinically important and useful to study the characteristics of marked hyperferritinemia. Previous studies of a relatively small number of patients which determined a primary cause as the etiology reported that either chronic transfusion or malignancy was the most frequent cause of marked hyperferritinemia [9][10][11]15]. One large study which similarly determined a primary cause reported hematological malignancy to be the most common cause followed by liver failure, HLH, and infection [12].…”

Hyperferritinaemia; laboratory implications

“…Thurlow et al 1 describe two novel mutations in the L-ferritin coding sequence associated with benign hyperferritinaemia showing abnormal ferritin glycosylation. Marshall et al 2 discuss causes of extreme hyperferritinaemia ( plasma ferritin concentration .10,000 mg/L).…”

“…Marshall et al . 2 discuss causes of extreme hyperferritinaemia (plasma ferritin concentration >10,000 μ g/L).…”