Can ferritin flag deadly macrophage-like sepsis?
In 5,121 Greek patients with infection and SIRS, macrophage activation-like syndrome (MALS) occurred in ~4% and independently predicted 10-day death; ferritin above 4420 ng/ml marked ~66% 28-day mortality.
Source
Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis
Study at a glance
- Design
- Cohort — Prospective Greek sepsis cohorts (test n=3417, validation n=1704) plus a Swedish ferritin-validation cohort (n=109) classifying macrophage activation-like syndrome (MALS)
- N
- N=5121 · 3417 test + 1704 validation patients with infection and SIRS; ferritin repeated on day 3 in 747; Swedish cohort n=109
- Population
- Adults with infection plus SIRS enrolled by the Hellenic Sepsis Study Group (plus an independent Swedish sepsis cohort)
- Outcome
- MALS frequency, 10-day mortality, and ferritin as a diagnostic/prognostic biomarker
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What they did
Assigned patients to test (n=3417) and validation (n=1704) cohorts, defined MALS by HScore and/or DIC plus hepatobiliary dysfunction, measured ferritin and cytokines, and checked 10-day mortality; ferritin was repeated on day 3 in 747 patients and in 109 Swedish patients.
What they found
MALS frequency was 3.7% (test) and 4.3% (validation). Ferritin >4420 ng/ml had >97% specificity for MALS and 66.7%/66% 28-day mortality (OR 4.07 in the test cohort). A <15% day-3 ferritin drop had >90% sensitivity for 10-day death.
The limits
What it doesn't show
This observational classification does not prove that treating high-ferritin MALS (e.g., with anakinra) saves lives; HScore was modified without bone-marrow hemophagocytosis, so MALS is not identical to classic MAS.
Key terms
- MALS
- Macrophage activation-like syndrome: sepsis with MAS/HLH-like hyperinflammation, diagnosed here by HScore and/or DIC+HBD.
- Ferritin
- Iron-storage protein; serum levels >4420 ng/ml were proposed as a high-specificity MALS biomarker.
- HScore
- Hemophagocytic syndrome score used (without bone-marrow points) as one MALS criterion.
- DIC
- Disseminated intravascular coagulation; with hepatobiliary dysfunction, one MALS definition.
- Anakinra
- IL-1 receptor antagonist previously linked in a post-hoc RCT subset to better survival in DIC+HBD sepsis.
- sCD163
- Soluble macrophage marker that rose with hyperferritinemia, supporting macrophage activation.
Flashcards
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Quiz yourself
MALS frequency in the test cohort was about:
Common questions
How common was MALS?
3.7% of the test cohort and 4.3% of the validation cohort.
What ferritin cutoff did they propose?
Above 4420 ng/ml, with >97% specificity for MALS.
How deadly was that cutoff?
About 66–66.7% died by day 28; 10-day mortality was ~45%.
What day-3 change was ominous?
Less than a 15% ferritin decrease, >90% sensitive for 10-day death.
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