What is the best course of action for a patient with hyperferritinemia, low iron binding capacity, elevated hemoglobin, and elevated hematocrit?

Evaluation and Management of High Ferritin, Low TIBC, Elevated Hemoglobin and Hematocrit

Immediate Diagnostic Priority

This constellation of findings—high ferritin, low iron binding capacity (indicating high transferrin saturation), and elevated hemoglobin/hematocrit—strongly suggests primary iron overload, most likely hereditary hemochromatosis, and requires immediate measurement of fasting transferrin saturation followed by HFE genetic testing if TS ≥45%. 1

Algorithmic Diagnostic Approach

Step 1: Confirm Transferrin Saturation

• Measure fasting transferrin saturation (TS) immediately to distinguish true iron overload from secondary causes 1, 2
• Low TIBC typically correlates with elevated TS (TS = serum iron/TIBC × 100) 3
• If TS ≥45% with elevated ferritin, proceed directly to HFE genotype testing for C282Y and H63D mutations 1, 2

Step 2: Obtain Baseline Liver Assessment

• Check ALT, AST, and complete metabolic panel to assess for liver disease 1
• The elevated hemoglobin/hematocrit in this scenario suggests the patient is not experiencing end-organ damage yet, but liver assessment is critical 4

Step 3: Risk Stratification Based on Ferritin Level

For ferritin <1000 μg/L:

• If patient has normal liver enzymes, no hepatomegaly, and age <40 years, proceed directly to therapeutic phlebotomy without liver biopsy 4, 1
• The negative predictive value for advanced fibrosis is 94% when ferritin <1000 μg/L with normal transaminases 1

For ferritin ≥1000 μg/L:

• Strongly consider liver biopsy if accompanied by elevated liver enzymes or platelet count <200,000/μL 4, 1
• This threshold indicates 20-45% prevalence of cirrhosis in C282Y homozygotes 1
• Refer to gastroenterologist or hepatologist for evaluation 1

Therapeutic Phlebotomy Protocol

Induction Phase

• Remove 500 mL blood weekly or biweekly as tolerated 4, 2
• Check hemoglobin/hematocrit before each phlebotomy 4
• Allow hemoglobin to fall no more than 20% from baseline 4
• Check ferritin every 10-12 phlebotomies 4
• Target ferritin of 50-100 μg/L for the induction phase endpoint 4, 1

Maintenance Phase

• Once target ferritin achieved, continue maintenance phlebotomy every 2-4 months to keep ferritin 50-100 μg/L 4, 1, 2
• Monitor ferritin every 3 months once stable 1

Critical Management Considerations

Avoid These Common Pitfalls

• Never supplement with vitamin C during phlebotomy therapy, as it accelerates iron mobilization and increases oxidative stress 4, 2
• Avoid iron supplements entirely 4
• Do not delay treatment while awaiting genetic testing if clinical suspicion is high 1
• Avoid raw shellfish due to risk of Vibrio vulnificus infection in iron-overloaded patients 4

Dietary Modifications

• No specific dietary iron restrictions are necessary during treatment 4
• The amount of iron that can be restricted through diet (2-4 mg/day) is minimal compared to phlebotomy removal (250 mg/week) 4

Special Considerations for Elevated Hemoglobin/Hematocrit

The elevated hemoglobin and hematocrit in this patient actually facilitates more aggressive phlebotomy without risk of anemia 4. This is advantageous as:

• Weekly phlebotomy can be maintained without interruption 4
• The patient can tolerate more rapid iron depletion 2
• This suggests early-stage disease before end-organ damage has occurred 5

Monitoring for Cardiac Complications

• If ferritin is severely elevated or patient has symptoms, obtain ECG and consider echocardiography to assess for cardiomyopathy 1
• Monitor for cardiac dysrhythmias during rapid iron mobilization, particularly in patients with advanced disease 2
• Do not delay phlebotomy while awaiting cardiac imaging if hemochromatosis is confirmed 1

Family Screening

• First-degree relatives should undergo genotyping as penetrance is higher in family members than the general population 1
• Screen with both ferritin and transferrin saturation 1

Expected Outcomes with Treatment

When initiated before severe iron overload develops, therapeutic phlebotomy:

• Prevents hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadism, arthropathy, and cardiomyopathy 5
• Substantially alleviates weakness, fatigue, elevated liver enzymes, right upper quadrant pain, and hyperpigmentation 5
• Does not reverse established cirrhosis, but prevents progression 4