Critical care
Can ferritin flag deadly macrophage-like sepsis?
Open access · cc by · source: Europe PMC
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.
How this study connects
Role on claims
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A cheap, widely available test identifies the subgroup, which is what makes it actionable.
A small, identifiable subgroup of sepsis carries very high mortality. Macrophage activation-like syndrome occurred in 3.7% and 4.3% of two cohorts, with ferritin above 4420 ng/ml over 97% specific for it and associated with 28-day mortality around 66% (OR 4.07).
Evidence for the claim as stated.
These studies subdivide critical illness with very different evidentiary weight. Macrophage activation-like syndrome is defined by a specific threshold and validated in a second cohort, while the sepsis transcriptomic clusters rest on ten arrays with algorithms the authors acknowledge overfit small public datasets.
Evidence for the claim as stated.
Open questions
Tensions this paper is part of
From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.
These studies subdivide critical illness with very different evidentiary weight. Macrophage activation-like syndrome is defined by a specific threshold and validated in a second cohort, while the sepsis transcriptomic clusters rest on ten arrays with algorithms the authors acknowledge overfit small public datasets.
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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Inspect source passages
Can ferritin flag deadly macrophage-like sepsis?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Test n=3417 and validation n=1704.
Patients with infections and systemic inflammatory response syndrome were assigned to one test cohort ( n = 3417) and a validation cohort ( n = 1704).
MALS frequency 3.7% and 4.3%.
The frequency of MALS was 3.7% and 4.3% in the test and the validation cohort, respectively.
Key findings
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.
Methodology
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.
Limitations
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.
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