What is the appropriate management for a 78-year-old patient with fatigue, high iron saturation, low TIBC, and normal total iron levels?

Management of High Iron Saturation with Low TIBC in a 78-Year-Old with Fatigue

This clinical presentation—high iron saturation, low TIBC, and normal total iron—strongly suggests iron overload rather than iron deficiency, and the patient requires evaluation for hemochromatosis with phlebotomy as the primary treatment if confirmed. 1

Understanding the Laboratory Pattern

The combination of findings in this patient is critical to interpret correctly:

• High transferrin saturation (>45%) with low TIBC indicates iron overload, not iron deficiency 1
• This pattern is the opposite of iron deficiency anemia, where TIBC is elevated and saturation is low 1
• Low TIBC with high saturation suggests the body's iron-binding capacity is overwhelmed by excess iron stores 2

Immediate Diagnostic Workup

Essential Laboratory Tests

Complete the iron panel assessment: 1

• Serum ferritin (likely to be markedly elevated in iron overload)
• CRP to assess for inflammation that might affect ferritin interpretation 1
• Complete blood count to evaluate for other causes of fatigue 1
• Liver function tests (AST, ALT) as iron overload commonly affects the liver 1

Genetic Testing for Hemochromatosis

HFE gene testing should be performed to identify hereditary hemochromatosis, the most common cause of iron overload: 1

• Test for C282Y and H63D mutations
• C282Y homozygosity is the classic genetic pattern in hereditary hemochromatosis
• In patients of European origin, this is the most likely diagnosis with this laboratory pattern 1

Clinical Evaluation for Iron Overload Complications

The fatigue in this 78-year-old may be directly related to iron overload affecting end organs: 1

Assess for organ damage from iron deposition:

• Liver disease: Check for hepatomegaly, cirrhosis risk (ferritin >1,000 μg/L increases fibrosis risk) 1
• Cardiac involvement: Obtain ECG and echocardiography to evaluate for arrhythmias and cardiac dysfunction 1
• Endocrine dysfunction: Screen for diabetes and hypogonadism (common in iron overload) 1
• Joint disease: Evaluate for arthropathy, particularly affecting 2nd/3rd metacarpophalangeal joints, ankles, hips 1

Treatment Approach

Phlebotomy as Primary Therapy

If hemochromatosis or iron overload is confirmed, repeated phlebotomy (venesection) is the treatment of choice: 1

• Remove 450-500 mL of blood weekly initially until ferritin normalizes
• This is the most effective method to reduce systemic iron stores 1
• Continue maintenance phlebotomy as needed to keep ferritin in normal range 1

Important Contraindications

Do NOT give iron supplementation in this patient—the laboratory pattern indicates iron excess, not deficiency 1

This is a critical pitfall: fatigue with abnormal iron studies might reflexively prompt iron supplementation, but high saturation with low TIBC is the opposite indication.

Differential Diagnosis Considerations

While hemochromatosis is most likely, consider: 1

• Secondary iron overload from repeated transfusions (less likely without this history)
• Chronic liver disease affecting iron metabolism
• Dysmetabolic iron overload syndrome (metabolic syndrome with mild iron elevation)
• Other causes of fatigue unrelated to iron status (hypothyroidism, anemia of chronic disease, cardiac disease)

Follow-Up Monitoring

Once treatment is initiated: 1

• Recheck ferritin and iron studies every 8-10 weeks during active phlebotomy
• Monitor liver function and assess for improvement in fatigue
• Screen first-degree relatives for hemochromatosis if genetic diagnosis confirmed 1

The key distinction here is recognizing that this patient has iron overload requiring iron removal, not iron deficiency requiring supplementation—a critical diagnostic and therapeutic fork in the road.