What is the treatment for G6PD deficiency with iron overload and elevated liver enzymes?

Treatment for G6PD Deficiency with Iron Overload and Elevated Liver Enzymes

Therapeutic phlebotomy is the recommended first-line treatment for patients with G6PD deficiency who have iron overload, elevated liver enzymes, high bilirubin, and high ferritin levels. 1

Understanding the Condition

G6PD deficiency is the most common enzymatic disorder of red blood cells, affecting approximately 400 million people worldwide 2. When combined with iron overload (indicated by high ferritin, high iron, high iron saturation) and liver dysfunction (elevated AST, ALT, and bilirubin), this presents a complex clinical scenario requiring careful management.

Treatment Algorithm

1. Therapeutic Phlebotomy

• Initial regimen: Remove one unit of blood (200-250 mg iron) once or twice weekly as tolerated 1
• Pre-phlebotomy assessment: Check hemoglobin/hematocrit before each session
• Target: Reduce serum ferritin to 50-100 μg/L 1
• Monitoring: Check ferritin levels after every 10-12 phlebotomies (approximately every 3 months) 1
• Caution: Avoid reducing hematocrit/hemoglobin to <80% of starting value to prevent excessive anemia 1

2. Medication Management

• Avoid oxidative stressors that can trigger hemolysis in G6PD deficiency:
  • Nitrates, copper, sulfate, chlorite, chloramines, chlorates
  • Dapsone, benzocaine, prilocaine, lidocaine, tetracaine, cocaine mixed with aniline
  • Sulfonamides, nitroglycerine 1
  • Methylene blue is contraindicated in G6PD deficiency 1
  • Rasburicase is contraindicated 3

3. Monitoring During Treatment

• Liver function: Regular monitoring of AST, ALT
• Bilirubin levels: Serial monitoring
• Complete blood count: To detect hemolysis
• Iron studies: Ferritin, transferrin saturation, serum iron

Special Considerations for G6PD Deficiency with Iron Overload

1. Risk of hemolysis during phlebotomy:

   • Start with smaller volume phlebotomy and gradually increase as tolerated
   • Monitor for signs of hemolysis (dark urine, pallor, fatigue)
   • Consider longer intervals between phlebotomy sessions if hemolysis occurs

2. Dietary recommendations:

   • Avoid fava beans (known trigger for hemolysis) 4
   • Avoid vitamin C supplements and iron supplements 1
   • Maintain adequate hydration

3. Management of acute hemolysis:

   • If hemolysis occurs, immediately discontinue any potential triggering agents
   • Provide supportive care with IV hydration
   • Consider blood transfusion for severe anemia
   • In severe cases with unidentified trigger, plasmapheresis may be considered 5

Alternative Treatments for Patients Who Cannot Tolerate Phlebotomy

For patients with severe anemia or cardiovascular instability who cannot tolerate phlebotomy:

• Iron chelation therapy: Consider deferasirox (Exjade) at doses of 5-30 mg/kg/day based on iron overload severity 6
• Monitoring during chelation: Regular assessment of renal function, liver function, and auditory and visual function

Expected Outcomes

With proper treatment, patients can expect:

• Reduction of tissue iron stores to normal levels
• Improved liver function with normalization of elevated liver enzymes
• Reduction in skin pigmentation (if present)
• Reduction in abdominal pain (if present)
• Possible reversal of hepatic fibrosis (in approximately 30% of cases) 1

Potential Complications and Pitfalls

• Hemolytic crisis: Can be precipitated by oxidative stressors; requires immediate discontinuation of triggering agent and supportive care
• Iron deficiency: Avoid excessive phlebotomy leading to iron deficiency
• Hepatocellular carcinoma risk: Patients with cirrhosis should continue to be screened for HCC even after adequate phlebotomy 1

Follow-up Recommendations

• After achieving target ferritin levels (50-100 μg/L), assess for maintenance phlebotomy needs
• Some patients require monthly maintenance phlebotomy, while others may need only 1-2 units removed per year 1
• Continue monitoring liver function tests and iron studies every 3-6 months

By following this treatment approach, patients with G6PD deficiency complicated by iron overload and elevated liver enzymes can effectively manage their condition and prevent further complications.