What is the appropriate management for an elderly male patient with hyperferritinemia, normal hemoglobin levels, a neutrophil count of 8, and an MCHC of 319?

Management of Hyperferritinemia in an Elderly Male with Normal Hemoglobin

This patient's ferritin of 738 μg/L with normal hemoglobin (141 g/L) and elevated neutrophils most likely represents secondary hyperferritinemia from inflammation, infection, or metabolic syndrome rather than iron overload, and requires measurement of fasting transferrin saturation to guide further management. 1

Immediate Diagnostic Workup

The single most critical test is fasting transferrin saturation (TS), which distinguishes true iron overload from secondary causes of hyperferritinemia. 1, 2

Essential Laboratory Tests to Order Now:

• Fasting transferrin saturation (morning sample preferred) 1, 2
• Complete metabolic panel including ALT, AST, albumin to assess hepatocellular injury 1, 2
• Inflammatory markers: CRP and ESR to detect occult inflammation 1, 2
• Complete blood count with differential (already shows neutrophils 8 × 10⁹/L, suggesting possible inflammation) 2

Algorithmic Approach Based on Transferrin Saturation

If TS ≥45%: Suspect Primary Iron Overload

• Proceed immediately to HFE genetic testing for C282Y and H63D mutations 1, 2
• C282Y homozygotes confirm hereditary hemochromatosis 1, 2
• Since ferritin is <1000 μg/L with normal hemoglobin, the risk of advanced liver fibrosis is very low (negative predictive value 94%) 1
• If C282Y homozygote confirmed: initiate therapeutic phlebotomy targeting ferritin 50-100 μg/L without liver biopsy if age <40 years, normal liver enzymes, and no hepatomegaly 1, 2

If TS <45%: Secondary Hyperferritinemia (Most Likely in This Case)

Over 90% of elevated ferritin cases with TS <45% are NOT due to iron overload. 1, 2 The elevated neutrophil count (8 × 10⁹/L) strongly suggests an inflammatory or infectious process. 3, 2

Investigate These Common Causes:

• Active infection: Most prevalent trigger in elderly patients; ferritin rises acutely as an acute-phase reactant 3, 2
• Chronic liver disease: Alcohol consumption, NAFLD/metabolic syndrome, viral hepatitis B or C 1, 2
• Malignancy: Particularly lymphomas and solid tumors in elderly males; prevalence increases with age 3, 4
• Chronic inflammatory conditions: Rheumatologic diseases, chronic kidney disease 1, 2
• Metabolic syndrome: Check fasting glucose, lipid panel, assess for insulin resistance 1, 5

Risk Stratification by Ferritin Level

At 738 μg/L, this patient falls into the low-risk category for organ damage:

• Ferritin <1000 μg/L indicates low risk of advanced liver fibrosis even if iron overload is present 1, 2
• This level does NOT approach thresholds associated with significant complications (>1000 μg/L for liver damage risk, >7000-10,000 μg/L for HLH consideration) 3, 1
• In elderly hospitalized patients, ferritin >1000 μg/L is associated with poor prognosis, but this patient's level is below that threshold 6

Special Considerations for Elderly Patients

Elevated Neutrophils (8 × 10⁹/L) Warrant Specific Attention:

• Rule out occult infection as the primary driver of hyperferritinemia 3, 2
• Check for urinary tract infection, pneumonia, intra-abdominal infection 2
• Consider blood cultures if fever or systemic symptoms present 3

Exclude Life-Threatening Conditions:

While unlikely at ferritin 738 μg/L, hemophagocytic lymphohistiocytosis (HLH) must be considered if:

• Ferritin continues rising toward >7000-10,000 μg/L 3
• Patient develops fever, splenomegaly, cytopenias affecting ≥2 lineages 3
• Triglycerides ≥3.0 mmol/L or fibrinogen ≤1.5 g/L develop 3

HLH diagnostic criteria require 5 of 8 findings, including ferritin ≥500 μg/L, but ferritin alone is not specific. 3 In adults, malignancies (particularly lymphomas) and infections are the most common HLH triggers. 3

Management Strategy

Treat the Underlying Condition, Not the Ferritin Number

Do not initiate phlebotomy or iron chelation based on ferritin alone. 1, 2 Secondary hyperferritinemia requires treatment of the underlying disease:

• If infection identified: Appropriate antimicrobial therapy; ferritin will normalize with infection resolution 2
• If NAFLD/metabolic syndrome: Weight loss, metabolic syndrome management 1, 2
• If inflammatory condition: Disease-specific anti-inflammatory therapy 1
• If malignancy: Oncologic treatment 1

Avoid Iron Supplementation

Never supplement iron in patients with elevated ferritin, as this can worsen outcomes by promoting oxidative stress and bacterial growth. 1, 2

Critical Pitfalls to Avoid

1. Never use ferritin alone without transferrin saturation to diagnose iron overload—ferritin is an acute-phase reactant elevated in inflammation, liver disease, and malignancy independent of iron stores 1, 2, 7

2. Do not assume iron overload when TS <45%—in the general population, iron overload is NOT the most common cause of elevated ferritin 1, 2

3. Do not overlook occult malignancy in elderly males with persistent hyperferritinemia—lymphomas and solid tumors increase with age 3, 4

4. Do not delay evaluation for infection when neutrophils are elevated—infection is the most prevalent HLH trigger and causes acute ferritin elevation 3, 2

Monitoring Plan

• Recheck ferritin and TS in 3 months after addressing identified underlying conditions 1, 2
• If ferritin continues rising or exceeds 1000 μg/L, reassess for occult malignancy, chronic liver disease, or evolving inflammatory condition 1, 6
• If ferritin exceeds 4000-5000 μg/L with persistent fever, measure glycosylated ferritin fraction (<20% is 93% specific for Adult-Onset Still's Disease) 2, 5