What is the management approach for a patient with elevated ferritin levels, specifically regarding referral to hematology and gastroenterology (GI)?

Management of Elevated Ferritin: Referral Decision Algorithm

The appropriate referral for elevated ferritin depends critically on whether the patient has iron deficiency (low ferritin) versus iron overload (high ferritin), as these represent opposite clinical scenarios requiring different specialists: GI evaluation is indicated for iron deficiency anemia to identify bleeding sources or malabsorption, while hematology referral is appropriate for suspected iron overload syndromes when ferritin is markedly elevated (>1000 μg/L) without clear secondary cause. 1, 2

Critical First Step: Distinguish Iron Deficiency from Iron Overload

The term "elevated ferritin" requires immediate clarification, as ferritin serves dual roles:

• Iron deficiency context: Ferritin <45 ng/mL indicates iron deficiency requiring GI evaluation 1
• Iron overload context: Ferritin >1000 μg/L suggests true iron overload requiring hematology evaluation 1, 2
• Intermediate elevations (100-1000 μg/L): Usually reflect inflammation, malignancy, liver disease, or metabolic syndrome rather than iron overload 1, 2, 3

When to Refer to GASTROENTEROLOGY

Iron Deficiency Anemia (Low Ferritin)

Refer to GI when ferritin is LOW (<45 ng/mL) with anemia, as this indicates iron deficiency requiring evaluation for GI blood loss or malabsorption 1:

• Men with Hb <13 g/dL and ferritin <45 ng/mL: Strong recommendation for bidirectional endoscopy 1
• Postmenopausal women with Hb <12 g/dL and ferritin <45 ng/mL: Strong recommendation for bidirectional endoscopy 1
• Premenopausal women: Conditional recommendation; may trial iron supplementation first if younger and low risk 1

Pre-endoscopy workup 1:

• Test for H. pylori (non-invasive)
• Test for celiac disease (serology)
• Only proceed to endoscopy if these are negative or after treating positive results 1

GI conditions to exclude 1:

• Colorectal cancer/polyps (most critical in men and postmenopausal women)
• Gastric cancer
• Celiac disease (2-3% of iron deficiency anemia cases)
• Angiodysplasia
• Inflammatory bowel disease
• NSAID-related bleeding 1

When to Refer to HEMATOLOGY

True Iron Overload (High Ferritin)

Refer to hematology when ferritin is >1000 μg/L without clear secondary cause, or when hereditary hemochromatosis is suspected 1, 2:

Initial evaluation before hematology referral 1:

• Measure transferrin saturation (TS)
• If TS ≥45% AND elevated ferritin: Order HFE gene testing 1
• If ferritin >1000 μg/L with elevated ALT/AST and platelets <200: High risk for cirrhosis (80% in C282Y homozygotes) 1

Hematology referral is appropriate for 1, 2:

• Confirmed C282Y homozygosity or compound heterozygosity (C282Y/H63D)
• Ferritin >1000 μg/L with TS ≥45% suggesting primary iron overload
• Unclear etiology after excluding secondary causes
• Need for therapeutic phlebotomy management 1

Ferritin >1000 μg/L predicts need for liver biopsy to assess hepatic iron concentration and fibrosis in confirmed hemochromatosis 1

Secondary Causes of Elevated Ferritin (Usually Do NOT Require Hematology)

Ferritin 100-1000 μg/L is most commonly due to 2, 3, 4:

• Malignancy (most frequent cause in hospitalized patients) 3, 4
• Infection/inflammation 3, 4
• Liver disease (hepatocellular injury, hepatitis, cirrhosis) 2, 4
• Metabolic syndrome/obesity/diabetes 2
• Chronic kidney disease 1
• Alcohol consumption 2

These patients need evaluation of the underlying condition, not hematology referral 2, 3

Common Pitfalls to Avoid

Pitfall #1: Assuming elevated ferritin always means iron overload 1, 2

• Ferritin is an acute phase reactant
• 90% of elevated ferritin is NOT due to iron overload 2
• Always check transferrin saturation to distinguish true iron overload from inflammation 1

Pitfall #2: Missing iron deficiency in inflammatory states 1

• Patients with inflammation may have iron deficiency despite ferritin >45 ng/mL (usually <100 ng/mL) 1
• Check transferrin saturation, soluble transferrin receptor, or reticulocyte hemoglobin if suspected 1

Pitfall #3: Inappropriate hematology referral for secondary hyperferritinemia 2, 3

• Address underlying malignancy, infection, or liver disease first
• Reserve hematology referral for ferritin >1000 μg/L without clear cause 2

Pitfall #4: Delaying GI evaluation in iron deficiency 1

• Even mild anemia may indicate serious pathology (GI malignancy)
• Do not assume dietary insufficiency without complete evaluation 1

Practical Algorithm Summary

1. Check complete iron panel: Ferritin, transferrin saturation, hemoglobin 1

2. If ferritin LOW (<45 ng/mL) with anemia → GI referral for endoscopic evaluation after H. pylori/celiac testing 1

3. If ferritin HIGH (>1000 μg/L) with TS ≥45% → Hematology referral after HFE gene testing 1, 2

4. If ferritin moderately elevated (100-1000 μg/L) → Evaluate for secondary causes (malignancy, infection, liver disease, metabolic syndrome); refer to appropriate specialist for underlying condition 2, 3

5. If ferritin >1000 μg/L but TS normal → Likely secondary hyperferritinemia; investigate underlying inflammatory/malignant process before hematology referral 2, 3, 4