Ferritin: Difference between revisions
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*Normal range: approximately 20-200 ng/mL (women), 20-500 ng/mL (men); varies by lab and age | *Normal range: approximately 20-200 ng/mL (women), 20-500 ng/mL (men); varies by lab and age | ||
*For the emergency physician, ferritin is most useful as a '''marker of systemic inflammation and immune activation''', not just iron status | *For the emergency physician, ferritin is most useful as a '''marker of systemic inflammation and immune activation''', not just iron status | ||
*The | *The degree of elevation significantly narrows the differential diagnosis | ||
==Clinical Features== | ==Clinical Features== | ||
| Line 46: | Line 46: | ||
===ED Pearls=== | ===ED Pearls=== | ||
* | *Ferritin >5× the upper limit of normal has a limited differential: AOSD/sJIA, MAS/HLH, hemochromatosis, hepatocellular injury, renal failure with iron overload | ||
*'''Ferritin >10,000 ng/mL''' should be considered '''MAS/HLH until proven otherwise''' — this is a medical emergency | *'''Ferritin >10,000 ng/mL''' should be considered '''MAS/HLH until proven otherwise''' — this is a medical emergency | ||
*A '''rapidly rising ferritin''' (doubling over hours to days) is more concerning than a static elevation and should prompt evaluation for MAS/HLH | *A '''rapidly rising ferritin''' (doubling over hours to days) is more concerning than a static elevation and should prompt evaluation for MAS/HLH | ||
* | *Ferritin:ESR ratio >21.5 in a patient with known or suspected [[Systemic JIA|sJIA]] is suggestive of MAS (ESR falls as fibrinogen is consumed, while ferritin skyrockets)<ref name="Eloseily2019">Eloseily EM, Minoia F, Engel B, et al. Ferritin to Erythrocyte Sedimentation Rate Ratio: Simple Measure to Identify Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. ACR Open Rheumatol. 2019;1(6):345-349.</ref> | ||
*'''Glycosylated ferritin fraction ≤20%''' (if available) is relatively specific for AOSD (normal is ~50-80%); not widely available as a stat test<ref name="Fautrel2001">Fautrel B, Le Moël G, Saint-Marcoux B, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still's disease. J Rheumatol. 2001;28(2):322-9.</ref> | *'''Glycosylated ferritin fraction ≤20%''' (if available) is relatively specific for AOSD (normal is ~50-80%); not widely available as a stat test<ref name="Fautrel2001">Fautrel B, Le Moël G, Saint-Marcoux B, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still's disease. J Rheumatol. 2001;28(2):322-9.</ref> | ||
*A | *A normal ferritin does not exclude iron deficiency in the setting of concurrent inflammation (ferritin is an acute phase reactant); a ferritin <100 ng/mL with an elevated CRP may still represent iron deficiency | ||
==Evaluation== | ==Evaluation== | ||
===When to Order Ferritin in the ED=== | ===When to Order Ferritin in the ED=== | ||
* | *Suspected MAS/HLH: Any patient (especially children with sJIA or adults with AOSD) with unexplained cytopenias, coagulopathy, hepatitis, and persistent fever | ||
* | *[[Fever of unknown origin]]: Ferritin is part of the initial FUO workup — the degree of elevation can rapidly narrow the differential | ||
* | *Suspected [[Adult-onset Still's disease]] or [[Systemic JIA]]: Quotidian fevers, rash, arthritis, leukocytosis with negative ANA/RF | ||
* | *Undifferentiated [[sepsis]] not responding to treatment: Consider MAS/HLH if ferritin returns markedly elevated with falling platelets and falling ESR | ||
* | *Iron deficiency anemia workup: Microcytic anemia, fatigue, pica, heavy menses, GI blood loss | ||
* | *Suspected iron overload: Chronic transfusion patients, suspected hemochromatosis (elevated transferrin saturation + elevated ferritin) | ||
===Companion Labs to Order with Ferritin=== | ===Companion Labs to Order with Ferritin=== | ||
* | *ESR, CRP — interpret ferritin in context of inflammation; a falling ESR with rising ferritin = MAS | ||
* | *CBC with differential and peripheral smear — cytopenias, blasts | ||
* | *LFTs (AST, ALT, LDH) — hepatocellular injury contributes to ferritin elevation | ||
* | *Fibrinogen — low/falling fibrinogen + high ferritin = MAS/DIC | ||
* | *D-dimer, PT/PTT — coagulopathy assessment | ||
* | *Iron studies (serum iron, TIBC, transferrin saturation) — if iron deficiency or overload is the clinical question | ||
* | *Triglycerides — elevated in HLH/MAS | ||
==Management== | ==Management== | ||
*Ferritin is a | *Ferritin is a diagnostic marker, not a condition to treat directly | ||
*Management is directed at the | *Management is directed at the underlying cause: | ||
** | **Iron deficiency: oral or IV iron supplementation | ||
** | **Iron overload/hemochromatosis: phlebotomy or chelation therapy (hematology referral) | ||
** | **AOSD/sJIA: corticosteroids, IL-1 or IL-6 inhibitors (rheumatology) | ||
** | **MAS/HLH: high-dose IV methylprednisolone ± anakinra/cyclosporine (see [[Macrophage activation syndrome]]) | ||
** | **Hepatocellular injury: treat the underlying cause | ||
* | *Serial ferritin trending is valuable for monitoring response to treatment in MAS/HLH and AOSD — falling ferritin indicates therapeutic response | ||
==Disposition== | ==Disposition== | ||
*Disposition is determined by the | *Disposition is determined by the underlying diagnosis, not the ferritin level itself | ||
*However, | *However, ferritin >10,000 ng/mL should prompt ICU-level evaluation for MAS/HLH regardless of how well the patient appears at that moment | ||
*Markedly elevated ferritin (>1,000-5,000 ng/mL) without a clear explanation warrants admission or urgent outpatient follow-up within 24-48 hours | *Markedly elevated ferritin (>1,000-5,000 ng/mL) without a clear explanation warrants admission or urgent outpatient follow-up within 24-48 hours | ||
Latest revision as of 09:28, 22 March 2026
Background
- Ferritin is an intracellular protein that stores iron and releases it in a controlled fashion
- Serum ferritin reflects total body iron stores but is also an acute phase reactant — it rises with inflammation, infection, malignancy, and liver disease independent of iron status
- Normal range: approximately 20-200 ng/mL (women), 20-500 ng/mL (men); varies by lab and age
- For the emergency physician, ferritin is most useful as a marker of systemic inflammation and immune activation, not just iron status
- The degree of elevation significantly narrows the differential diagnosis
Clinical Features
Differential Diagnosis by Degree of Elevation
| Ferritin Level | Differential Diagnosis |
| Low (<20 ng/mL) |
|
| Mildly elevated (200-1,000 ng/mL) |
|
| Markedly elevated (1,000-10,000 ng/mL) |
|
| Extremely elevated (>10,000 ng/mL) |
|
ED Pearls
- Ferritin >5× the upper limit of normal has a limited differential: AOSD/sJIA, MAS/HLH, hemochromatosis, hepatocellular injury, renal failure with iron overload
- Ferritin >10,000 ng/mL should be considered MAS/HLH until proven otherwise — this is a medical emergency
- A rapidly rising ferritin (doubling over hours to days) is more concerning than a static elevation and should prompt evaluation for MAS/HLH
- Ferritin:ESR ratio >21.5 in a patient with known or suspected sJIA is suggestive of MAS (ESR falls as fibrinogen is consumed, while ferritin skyrockets)[1]
- Glycosylated ferritin fraction ≤20% (if available) is relatively specific for AOSD (normal is ~50-80%); not widely available as a stat test[2]
- A normal ferritin does not exclude iron deficiency in the setting of concurrent inflammation (ferritin is an acute phase reactant); a ferritin <100 ng/mL with an elevated CRP may still represent iron deficiency
Evaluation
When to Order Ferritin in the ED
- Suspected MAS/HLH: Any patient (especially children with sJIA or adults with AOSD) with unexplained cytopenias, coagulopathy, hepatitis, and persistent fever
- Fever of unknown origin: Ferritin is part of the initial FUO workup — the degree of elevation can rapidly narrow the differential
- Suspected Adult-onset Still's disease or Systemic JIA: Quotidian fevers, rash, arthritis, leukocytosis with negative ANA/RF
- Undifferentiated sepsis not responding to treatment: Consider MAS/HLH if ferritin returns markedly elevated with falling platelets and falling ESR
- Iron deficiency anemia workup: Microcytic anemia, fatigue, pica, heavy menses, GI blood loss
- Suspected iron overload: Chronic transfusion patients, suspected hemochromatosis (elevated transferrin saturation + elevated ferritin)
Companion Labs to Order with Ferritin
- ESR, CRP — interpret ferritin in context of inflammation; a falling ESR with rising ferritin = MAS
- CBC with differential and peripheral smear — cytopenias, blasts
- LFTs (AST, ALT, LDH) — hepatocellular injury contributes to ferritin elevation
- Fibrinogen — low/falling fibrinogen + high ferritin = MAS/DIC
- D-dimer, PT/PTT — coagulopathy assessment
- Iron studies (serum iron, TIBC, transferrin saturation) — if iron deficiency or overload is the clinical question
- Triglycerides — elevated in HLH/MAS
Management
- Ferritin is a diagnostic marker, not a condition to treat directly
- Management is directed at the underlying cause:
- Iron deficiency: oral or IV iron supplementation
- Iron overload/hemochromatosis: phlebotomy or chelation therapy (hematology referral)
- AOSD/sJIA: corticosteroids, IL-1 or IL-6 inhibitors (rheumatology)
- MAS/HLH: high-dose IV methylprednisolone ± anakinra/cyclosporine (see Macrophage activation syndrome)
- Hepatocellular injury: treat the underlying cause
- Serial ferritin trending is valuable for monitoring response to treatment in MAS/HLH and AOSD — falling ferritin indicates therapeutic response
Disposition
- Disposition is determined by the underlying diagnosis, not the ferritin level itself
- However, ferritin >10,000 ng/mL should prompt ICU-level evaluation for MAS/HLH regardless of how well the patient appears at that moment
- Markedly elevated ferritin (>1,000-5,000 ng/mL) without a clear explanation warrants admission or urgent outpatient follow-up within 24-48 hours
See Also
- Macrophage activation syndrome
- Hemophagocytic lymphohistiocytosis
- Adult-onset Still's disease
- Systemic JIA
- Iron deficiency anemia
- Fever of unknown origin
- Sepsis (Main)
External Links
References
- ↑ Eloseily EM, Minoia F, Engel B, et al. Ferritin to Erythrocyte Sedimentation Rate Ratio: Simple Measure to Identify Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. ACR Open Rheumatol. 2019;1(6):345-349.
- ↑ Fautrel B, Le Moël G, Saint-Marcoux B, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still's disease. J Rheumatol. 2001;28(2):322-9.