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

Management of G6PD Deficiency with Iron Overload and Elevated Liver Enzymes

Therapeutic phlebotomy is the first-line treatment for patients with G6PD deficiency who have iron overload, elevated liver enzymes, and high bilirubin 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 a patient with G6PD deficiency presents with:

• High ferritin
• High iron
• High iron saturation
• High bilirubin
• Elevated AST/ALT

This constellation of findings suggests iron overload with hepatic involvement, which requires prompt treatment to prevent progression to cirrhosis and other complications.

Treatment Algorithm

First-Line Treatment: Therapeutic Phlebotomy

1. Initial Phlebotomy Protocol:

   • Remove one unit of blood (200-250 mg iron) once or twice weekly as tolerated 1
   • Monitor hematocrit/hemoglobin before each session
   • Do not reduce hematocrit/hemoglobin to <80% of starting value 1
   • Continue until serum ferritin drops to 50-100 μg/L 1

2. Monitoring During Treatment:

   • Check serum ferritin after every 10-12 phlebotomies (approximately every 3 months) 1
   • Monitor liver enzymes (AST, ALT) and bilirubin regularly
   • As target ferritin (50-100 μg/L) is approached, test more frequently to avoid iron deficiency 1

3. Maintenance Phase:

   • After achieving target ferritin levels, assess need for maintenance phlebotomy
   • Frequency varies among individuals (monthly to 1-2 units per year) 1

Special Considerations for G6PD Deficiency

1. Avoid Oxidative Stressors:

   • Strictly avoid medications that can trigger hemolysis in G6PD deficiency, including:
     • Methylene blue (contraindicated) 1
     • Dapsone
     • Nitrofurantoin
     • Phenazopyridine
     • Primaquine
     • Rasburicase 3

2. Dietary Modifications:

   • Avoid fava beans, which are a common trigger for hemolysis 4
   • Avoid iron supplements and vitamin C supplements during treatment 1

3. Monitoring for Hemolysis:

   • Watch for signs of acute hemolysis: darkening of urine, pallor, fatigue, jaundice
   • If hemolysis occurs, discontinue any potential triggers immediately

Management of Complications

If Acute Hemolysis Develops:

1. Immediately discontinue any potential triggering agents
2. Provide supportive care with intravenous hydration
3. Monitor hemoglobin levels closely
4. Consider plasmapheresis for severe hemolysis with unknown trigger 5
5. Blood transfusion may be required for severe anemia

For Persistent Iron Overload Despite Phlebotomy:

In patients who cannot tolerate phlebotomy or have persistent iron overload:

• Consider iron chelation therapy with deferasirox (oral) 6
• Starting dose based on liver iron concentration (LIC)
• Monitor for side effects and efficacy with regular ferritin and LIC measurements 6

Expected Outcomes

With appropriate treatment, patients can expect:

• Reduction of tissue iron stores to normal levels
• Normalization of elevated liver enzymes
• Reduction in bilirubin levels
• Improved sense of well-being and energy levels
• Reduction in skin pigmentation
• Potential reversal of hepatic fibrosis (in approximately 30% of cases) 1

Important Caveats

1. Phlebotomy in G6PD Deficiency:

   • While phlebotomy is generally safe in G6PD deficiency, monitor closely for signs of hemolysis
   • Consider smaller volume phlebotomy if patient shows signs of hemolysis

2. Cirrhosis Risk:

   • If cirrhosis has already developed, it will not be reversed with iron removal 1
   • Patients with cirrhosis should continue to be screened for hepatocellular carcinoma even after adequate phlebotomy 1

3. Medication Safety:

   • Document G6PD status prominently in medical records
   • Establish a monitoring protocol for high-risk situations 4
   • Safe medications include benzodiazepines, codeine/derivatives, propofol, fentanyl, and ketamine 7

By following this treatment approach, patients with G6PD deficiency and iron overload can achieve significant improvement in their condition and prevent progression to more serious complications.