What should be done for a patient who is not receiving prophylactic phlebotomy (blood draw) for iron overload?

Management of Patients Not Receiving Prophylactic Phlebotomy for Iron Overload

If a patient with iron overload is not receiving prophylactic phlebotomy, you should immediately initiate weekly therapeutic phlebotomy (removing 400-500 mL of blood per session) and continue until serum ferritin reaches 50-100 μg/L, as this prevents irreversible complications including cirrhosis, hepatocellular carcinoma, and death. 1, 2

Why Prophylactic Phlebotomy Cannot Be Delayed

The evidence is unequivocal: survival returns to normal population levels only when phlebotomy is initiated before cirrhosis and diabetes develop. 1, 3 Once cirrhosis is established, it cannot be reversed by phlebotomy, and hepatocellular carcinoma accounts for 30% of all hemochromatosis-related deaths even after adequate iron removal. 1 This creates a narrow window for intervention that closes permanently once advanced fibrosis develops.

The American Association for the Study of Liver Diseases strongly favors proceeding to prophylactic phlebotomy in asymptomatic individuals with markers of iron overload who tolerate and adhere to the regimen, even when ferritin levels are only moderately elevated (e.g., 800 μg/L) with normal liver tests. 1 The rationale is compelling: treatment is easy, safe, inexpensive, potentially provides societal benefit through blood donation, and there are no reliable indicators of who will develop life-threatening complications. 1

Immediate Treatment Protocol

Initial Therapeutic Phase

• Remove one unit of blood (450-500 mL) weekly or twice weekly as tolerated, with each unit containing approximately 200-250 mg of iron 1, 2, 3
• Check hemoglobin or hematocrit before every phlebotomy session to avoid reducing it to less than 80% of the starting value 1, 2
• Postpone phlebotomy if hemoglobin falls below 12 g/dL and discontinue if below 11 g/dL, resuming only when anemia resolves 3
• Monitor serum ferritin every 10-12 phlebotomies (approximately every 3 months) during initial treatment, then more frequently as target range approaches 1, 2, 3
• Continue therapeutic phlebotomy until ferritin drops to 50-100 μg/L—do not induce iron deficiency 1, 2, 3

Maintenance Phase

After achieving target ferritin levels, the approach varies by individual iron reaccumulation rates:

• Some patients require monthly maintenance phlebotomy, while others need only 1-2 units per year 1
• Not all patients with hemochromatosis reaccumulate iron, so maintenance frequency must be individualized 1
• Maintain serum ferritin between 50-100 μg/L through periodic blood removal 2, 4
• Monitor ferritin monthly during initial therapy and every 3-6 months during maintenance 2

Critical Pitfalls to Avoid

The "Wait and See" Trap

The most dangerous pitfall is delaying treatment in asymptomatic patients with moderate iron overload. Current longitudinal data are limited, and while some patients may never progress to serious problems, there are no available, reliable indicators of who will develop complications. 1 The rate of ferritin increase may prove useful in the future, but this remains unvalidated. 1

Vitamin C Supplementation

Patients must avoid vitamin C supplements entirely or limit intake to ≤500 mg/day. 2, 3 Pharmacologic doses of vitamin C accelerate iron mobilization to levels that may saturate circulating transferrin, resulting in increased pro-oxidant and free-radical activity. 1 In patients with advanced cardiac disease, rapid iron mobilization increases the risk of sudden death from cardiac arrhythmias due to toxic low-molecular-weight iron chelates. 1

Dietary Restrictions

• Avoid all medicinal iron and iron-fortified foods including fortified breakfast cereals 2, 3, 4
• Patients with cirrhosis must completely abstain from alcohol 3
• Avoid raw shellfish due to Vibrio vulnificus infection risk in patients with cirrhosis and iron overload 2, 5

Special Considerations for Advanced Disease

Patients with Cirrhosis

If cirrhosis is already present when treatment begins:

• Phlebotomy can reduce portal hypertension but cannot reverse established cirrhosis 1, 3
• Hepatocellular carcinoma screening must continue every 6 months for life, even after successful iron depletion, as the risk persists 1, 3
• Hepatic fibrosis reverses in approximately 30% of cases, but this benefit is lost once cirrhosis develops 1, 3

When Phlebotomy Is Not Feasible

If the patient cannot tolerate phlebotomy due to anemia or other contraindications:

• Iron chelation therapy with deferoxamine (20-40 mg/kg/day) becomes the treatment of choice 1, 6
• Newer oral chelators including deferiprone and deferasirox are available for patients intolerant of parenteral therapy 6, 7
• Combined subcutaneous deferoxamine and oral deferiprone shows particular promise 6
• Combination therapy with phlebotomy plus chelation reduces ferritin more rapidly (147 ng/ml/month) compared to either modality alone 8

Expected Outcomes with Timely Treatment

When phlebotomy is initiated before cirrhosis develops, patients can expect:

• Survival equivalent to the normal population 1, 3
• Improved sense of well-being and energy level 1
• Improved cardiac function and diabetes control 1, 3
• Normalization of elevated liver enzymes 1, 3
• Reduction in abdominal pain and skin pigmentation 1
• Elimination of hepatocellular carcinoma risk if iron removal achieved before cirrhosis 1

However, certain manifestations show minimal or no improvement:

• Arthropathy does not improve with phlebotomy 1
• Testicular atrophy is irreversible 1
• Established cirrhosis cannot be reversed 1

Bottom Line

The decision to withhold prophylactic phlebotomy in a patient with documented iron overload is indefensible given the overwhelming evidence for benefit and the irreversibility of complications once they develop. Treatment should be initiated immediately unless specific contraindications exist, in which case iron chelation therapy provides an alternative approach. 1, 2