What is the management plan for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency?

Management of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

The cornerstone of G6PD deficiency management is prevention of hemolytic crises through strict avoidance of oxidative triggers, including specific medications, foods, and prompt treatment of infections, with screening recommended before administering any oxidant drug in at-risk populations. 1, 2

Screening and Diagnosis

• Screen all patients with Mediterranean, African, Indian, or Southeast Asian ancestry before prescribing oxidant drugs 1, 2
• Qualitative screening is sufficient for initial assessment, though quantitative testing may be needed for borderline cases 2
• Consider screening in patients presenting with acute hemolysis after exposure to fava beans, certain medications, or infections 3
• Testing should be performed before administering rasburicase, primaquine, dapsone, pegloticase, or methylene blue 3

Medications to Strictly Avoid

High-risk medications that must be avoided entirely:

• Primaquine - causes severe hemolytic anemia and is strictly contraindicated 1, 2
• Dapsone - potent oxidant causing methemoglobinemia and red blood cell hemolysis 1, 2
• Methylene blue (methylthioninium chloride) - causes severe hemolytic anemia and is contraindicated; paradoxically worsens G6PD-related hemolysis 1, 2
• Rasburicase - causes severe hemolytic anemia 2

Medications Requiring Caution

• Local anesthetics (benzocaine, prilocaine, lidocaine, tetracaine) can precipitate methemoglobinemia and should be used cautiously 1
• Sulfonamides including sulfamethoxazole/cotrimoxazole may pose risk, though recent data suggests they may be safer than previously thought 1
• Chloroquine/hydroxychloroquine in standard doses appears relatively safe in most G6PD deficient patients 2

Dietary Restrictions

Fava beans are the most critical dietary trigger to avoid:

• Fava beans caused hemolysis in 32.6% of cases in a large Egyptian study 4
• Other legumes requiring avoidance include falafel (19.4%), chickpeas (10.8%), broad beans (7.6%), green peas (4.4%), peanuts (3.8%), lentils (2.8%), and black-eyed peas (2%) 4

Infection Management

• Infections are the second most common trigger of hemolysis (12.4% of cases) 4
• Promptly treat pneumonia, tonsillitis, typhoid fever, hepatitis A, and urinary tract infections to prevent oxidative stress 4
• Monitor for hemolysis during any infectious illness 4

Recognition of Hemolytic Crisis

Patients typically present 24-72 hours after exposure to triggers with:

• Pallor (universal finding) 4
• Dark red urine/hemoglobinuria (89.6% of cases) 4
• Jaundice (87.8% of cases) 4
• Additional symptoms include fatigue, back pain, and abdominal pain 3

Variant-Specific Considerations

• Mediterranean variant (Gdmed) - causes more severe, potentially life-threatening hemolysis; found predominantly in Mediterranean, Indian, and Southeast Asian populations 2
• African variant (GdA-) - typically causes milder, self-limited hemolysis; found in 10-15% of Black individuals 2
• The severity of reactions varies significantly based on genetic variant, requiring more vigilant monitoring in Mediterranean variant carriers 1, 2

Treatment of Acute Hemolysis

• Most individuals with G6PD deficiency remain asymptomatic throughout life unless exposed to triggers 3, 5
• Acute hemolytic anemia can be managed effectively with prompt diagnosis and supportive care 5
• For methemoglobinemia in G6PD-deficient patients, use ascorbic acid (Vitamin C) at 0.2-1.0 g/day orally in divided doses, NOT methylene blue 1

Common Pitfalls

• Testing only for the c.202G>A variant misses 13% of individuals with deficiency-causing variants 6
• Over 800 G6PD variants exist, with approximately 200 mutations well-characterized 5, 7
• Females heterozygous for G6PD deficiency may require molecular analysis rather than enzymatic testing for accurate diagnosis 3
• The highest prevalence of hemolytic crises occurs in children aged 1-3 years, with mean age of first presentation at 22.8 months 4