is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin
is hemophagocytic lymphohistiocytosis
. We analyze ferritin
levels to differentiate hemophagocytic lymphohistiocytosis
from other causes of hyperferritinemia
in a mixed cohort of critically ill patients.
Retrospective observational study.
Adult surgical, anesthesiologic, and medical ICUs of a university hospital.
Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité – Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin
value and hyperferritinemia
(≥ 500 µg/L).
Measurements and Main Results:
Patients were categorized into hemophagocytic lymphohistiocytosis
, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis
diagnosis was based on Hemophagocytic Lymphohistiocytosis
-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia
, 40 were considered to have hemophagocytic lymphohistiocytosis
(1.52%). Maximum ferritin
levels were highest in hemophagocytic lymphohistiocytosis
patients compared with all other disease groups (each p
< 0.001). Sepsis and septic shock patients had higher maximum ferritin
levels than patients with other diagnoses (each p
< 0.001). A maximum ferritin
value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis
(area under the curve, 0.963; 95% CI, 0.949–0.978). Of all subgroups with other diagnoses, maximum ferritin
levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin
levels were associated with increased in-hospital mortality
(odds ratio, 1.518 per log µg/L [95% CI, 1.384–1.665 per log µg/L]; p
This is the largest study of patients with ferritin
available in a mixed ICU cohort. Ferritin
levels in patients with hemophagocytic lymphohistiocytosis
, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin
levels observed in hemophagocytic lymphohistiocytosis
patients. Maximum ferritin
of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis
in ICU. The inclusion of ferritin
into the sepsis laboratory panel is warranted.