Background/Purpose:

Inreased ferritin levels are protective during infection whereas but very very high level are associated with MAS in rheumatologic disease cTo determine frequency of macrophage activation syndrome (MAS) in a sepsis cohort defined by using ferritin level (> 2,000), and to compare outcome, organ involvement and response to anakinra in sepsis across levels of Ferritinemia. 

Methods:

Remaining sera and data from “interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial” (Opal, et. al. Crit Care Med. 1997 Jul;25(7):1115-24.) was analysed. Ferritin was measured in the remaining sera of de-identified subjects from this study (levels beyond 6,000 were not further diluted). Subgroups were defined based on serum ferritin ranges (0-499, 500-999, 1000-1999, above 2000 μg/L). Post hoc statistical analysis included: descriptive statistics, rank test, ANOVA, Cox regression. 

Results:

Sera and data were available for ferritin measurement in 120/756 original study cohort (ages 22-85; 41.6% women). Demographics and  28-day outcome with or without anakinra in the ferritin subgroups are shown in Table. The Ferritin subgroup 500-999 had higher 28 day survival than other subgroups (18/21, 85.7%)(p < .05?), which was decreased with anakinra (100% alive in placebo vs. 82.4% with anakinra). The Ferritin subgroup >2000 (24/29, 24.2%) showed lower 28-day survival, which was increased with anakinra (40% with placebo vs. 57.9% with anakinra).  

Conclusion:

As hypothesized, an increased Ferritin 500-1000 showed  a  protective inflammatory response in adult severe sepsis patients, whereasvery high Ferritin levels > 2,000 μg/L may signify immune dysregulation and concurrent MAS ( 25% of adult severe sepsis patients). Given the high mortality of unrecognized MAS in adults with rheumatic diseases (up to 64% reported) further stuies are warranted both evaluating ferritin in the diagnosis of, and anakinra in the treatment of  severe sepsis associated MAS (Ferritin > 2,000)