What is the best management approach for an elderly patient with hemochromatosis?

Management of Hemochromatosis in Elderly Patients

Therapeutic phlebotomy remains the first-line treatment for elderly patients with hemochromatosis and evidence of iron overload, with the primary goal of achieving and maintaining serum ferritin levels between 50-100 μg/L to reduce morbidity and mortality. 1

Initial Assessment and Treatment Indications

Initiate phlebotomy therapy in elderly patients when:

• Serum ferritin ≥300 μg/L in men or ≥200 μg/L in women, regardless of symptoms 2
• Evidence of iron overload with transferrin saturation >45% 2
• Before development of cirrhosis and diabetes, as early treatment significantly reduces morbidity and mortality 1

The most recent EASL guidelines (2022) emphasize that patients with hemochromatosis and evidence of iron overload should undergo iron depletion therapy as a strong recommendation 1. This applies to elderly patients, though they require closer monitoring due to age-related risk of toxicity 3.

Phlebotomy Protocol for Elderly Patients

Induction Phase

• Remove 450-500 mL (1 unit) of blood weekly or biweekly as tolerated 1, 3
• Each unit removes approximately 200-250 mg of iron 1, 3
• Check hemoglobin or hematocrit before each phlebotomy 1
  • Reduce frequency if hemoglobin falls below 12 g/dL 3
  • Pause treatment if hemoglobin falls below 11 g/dL 1
  • Do not allow hemoglobin/hematocrit to drop more than 20% from baseline 1, 2
• Monitor serum ferritin every 10-12 phlebotomies (approximately every 3 months) 1, 3
• Continue until ferritin reaches 50-100 μg/L 1
• This phase may take 2-3 years in patients with significant iron overload (>30g total body iron) 1, 3

Maintenance Phase

• Maintain serum ferritin between 50-100 μg/L 1, 3
• Frequency varies among individuals (typically every 2-4 months) due to variable iron reaccumulation rates 1, 3
• Monitor ferritin every 6 months during maintenance 3
• Avoid inducing iron deficiency—this should be prevented 1

Special Considerations for Elderly Patients

Age-related monitoring is critical:

• Elderly patients require closer monitoring for toxicity 3
• Primary care physicians and gastroenterologists can manage phlebotomy directly without hematology consultation in uncomplicated cases 4
• Phlebotomy is safe, effective, and inexpensive when properly monitored 4

Alternative Treatment Options

Erythrocytapheresis may be considered as an alternative to standard phlebotomy 1:

• Requires fewer procedures during induction phase 1
• Results in fewer hemodynamic changes compared to phlebotomy 1
• Use depends on availability, local expertise, and patient preferences 1
• Target ferritin remains 50-100 μg/L 1

Iron chelation therapy (deferasirox) is second-line only 1, 5:

• Reserved for selected cases after careful risk assessment 1
• Contraindicated if eGFR <40 mL/min/1.73 m² 5
• Carries significant risks including acute kidney injury, hepatic failure, and gastrointestinal hemorrhage 5
• Not appropriate for primary hemochromatosis when phlebotomy is tolerated 1

Expected Clinical Outcomes

Symptoms that respond well to phlebotomy: 1

• Malaise and fatigue
• Skin pigmentation
• Insulin requirements in diabetics
• Abdominal pain
• Improved sense of well-being and energy level
• Improved cardiac function

Symptoms that respond poorly or not at all: 1

• Arthropathy (less responsive)
• Hypogonadism (less responsive)
• Advanced cirrhosis (no response)

Hepatic fibrosis may regress in approximately 30% of cases 1, but established cirrhosis does not reverse 1.

Critical Pitfalls to Avoid

Dietary and medication management: 1, 3, 4

• Avoid vitamin C supplements entirely during treatment—they accelerate iron mobilization to dangerous levels 3, 4
• Avoid iron supplements and daily red meat consumption 1
• Avoid moderate to heavy alcohol intake; patients with advanced liver disease should abstain completely 1
• Dietary iron restriction is unnecessary—it removes only 2-4 mg/day compared to 200-250 mg per phlebotomy 3
• Avoid raw or undercooked seafood and contact of wounds with seawater (Vibrio vulnificus risk) 1

Monitoring pitfalls:

• Do not delay treatment by routinely referring to hematology for uncomplicated cases 4
• Monitor for unexplained reduction in phlebotomy need or development of iron deficiency—this warrants complete workup for alternative causes 1
• Avoid inducing iron deficiency through excessive phlebotomy 1

Long-term Management in Cirrhotic Patients

For elderly patients with established cirrhosis: 1

• Continue hepatocellular carcinoma (HCC) screening even after successful iron depletion—cancer risk persists 1, 4
• HCC accounts for approximately 30% of hemochromatosis-related deaths 1
• HCC is exceptionally rare in non-cirrhotic hemochromatosis, providing strong rationale for early treatment 1

Survival benefit is well-established: Initiation of phlebotomy before development of cirrhosis and diabetes significantly reduces morbidity and mortality 1, making early and consistent treatment essential even in elderly patients who can tolerate the procedure.