Ferritin - Revision history

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← Older revision		Revision as of 06:44, 22 March 2026
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	[[Category:Heme/Onc]]		[[Category:Heme/Onc]]
	[[Category:Critical Care]]		[[Category:Critical Care]]
			[[Category:Labs]]

Ostermayer: Created page with "==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 i..."

2026-03-09T19:47:01Z

Created page with "==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 i..."

New page

==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===

{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Ferritin Level'''
| align="center" style="background:#f0f0f0;"|'''Differential Diagnosis'''
|-
| '''Low (<20 ng/mL)''' ||
*'''[[Iron deficiency anemia]]''' (most common cause of low ferritin)
*Chronic blood loss (GI, menstrual)
*Malabsorption ([[celiac disease]])
*Pregnancy
|-
| '''Mildly elevated (200-1,000 ng/mL)''' ||
*Acute/chronic inflammation (infection, autoimmune disease)
*[[Chronic liver disease]], [[hepatitis]], steatohepatitis
*[[Chronic kidney disease]]
*Chronic [[alcohol]] use
*Metabolic syndrome/obesity
*Malignancy
*Iron supplementation/transfusion
*[[Hyperthyroidism]]
|-
| '''Markedly elevated (1,000-10,000 ng/mL)''' ||
*'''[[Adult-onset Still's disease]]''' (AOSD) / '''[[Systemic JIA]]''' (sJIA)
*'''[[Hemophagocytic lymphohistiocytosis]]''' (HLH) / '''[[Macrophage activation syndrome]]''' (MAS)
*'''Hemochromatosis''' (hereditary or transfusional iron overload)
*'''Hepatocellular injury''' (acute hepatitis, [[acetaminophen toxicity]], ischemic hepatitis)
*Hematologic malignancy ([[leukemia]], [[lymphoma]])
*'''[[Sepsis]]''' (severe)
*Renal failure (especially on dialysis with IV iron)
|-
| '''Extremely elevated (>10,000 ng/mL)''' ||
*'''[[Macrophage activation syndrome]]''' / '''HLH''' — most likely diagnosis
*'''[[Adult-onset Still's disease]]''' with MAS
*Massive hepatocellular necrosis
*Transfusional iron overload (chronic transfusion-dependent anemias)
|}

===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 [[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>
*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==
*[https://www.mdcalc.com/calc/4053/hscore-reactive-hemophagocytic-syndrome MDCalc - HScore for Reactive Hemophagocytic Syndrome]

==References==
{{reflist|2}}

[[Category:Heme/Onc]]
[[Category:Critical Care]]

← Older revision		Revision as of 09:28, 22 March 2026
Line 4:		Line 4:
	*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 ~~'''~~degree of elevation~~'''~~ significantly narrows the differential diagnosis		*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 >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>		*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 ~~'''~~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		*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		*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		*[[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		*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		*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		*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)		*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		*ESR, CRP — interpret ferritin in context of inflammation; a falling ESR with rising ferritin = MAS
	*~~'''~~CBC with differential and peripheral smear~~'''~~ — cytopenias, blasts		*CBC with differential and peripheral smear — cytopenias, blasts
	*~~'''~~LFTs (AST, ALT, LDH)~~'''~~ — hepatocellular injury contributes to ferritin elevation		*LFTs (AST, ALT, LDH) — hepatocellular injury contributes to ferritin elevation
	*~~'''~~Fibrinogen~~'''~~ — low/falling fibrinogen + high ferritin = MAS/DIC		*Fibrinogen — low/falling fibrinogen + high ferritin = MAS/DIC
	*~~'''~~D-dimer, PT/PTT~~'''~~ — coagulopathy assessment		*D-dimer, PT/PTT — coagulopathy assessment
	*~~'''~~Iron studies (serum iron, TIBC, transferrin saturation)~~'''~~ — if iron deficiency or overload is the clinical question		*Iron studies (serum iron, TIBC, transferrin saturation) — if iron deficiency or overload is the clinical question
	*~~'''~~Triglycerides~~'''~~ — elevated in HLH/MAS		*Triglycerides — elevated in HLH/MAS

	==Management==		==Management==
	*Ferritin is a ~~'''~~diagnostic marker~~'''~~, not a condition to treat directly		*Ferritin is a diagnostic marker, not a condition to treat directly
	*Management is directed at the ~~'''~~underlying cause:~~'''~~		*Management is directed at the underlying cause:
	**~~'''~~Iron deficiency:~~'''~~ oral or IV iron supplementation		**Iron deficiency: oral or IV iron supplementation
	**~~'''~~Iron overload/hemochromatosis:~~'''~~ phlebotomy or chelation therapy (hematology referral)		**Iron overload/hemochromatosis: phlebotomy or chelation therapy (hematology referral)
	**~~'''~~AOSD/sJIA:~~'''~~ corticosteroids, IL-1 or IL-6 inhibitors (rheumatology)		**AOSD/sJIA: corticosteroids, IL-1 or IL-6 inhibitors (rheumatology)
	**~~'''~~MAS/HLH:~~'''~~ high-dose IV methylprednisolone ± anakinra/cyclosporine (see [[Macrophage activation syndrome]])		**MAS/HLH: high-dose IV methylprednisolone ± anakinra/cyclosporine (see [[Macrophage activation syndrome]])
	**~~'''~~Hepatocellular injury:~~'''~~ treat the underlying cause		**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		*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 ~~'''~~underlying diagnosis~~'''~~, not the ferritin level itself		*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		*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