How is G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency managed?

Management of G6PD Deficiency

The cornerstone of G6PD deficiency management is prevention of hemolytic crises through strict avoidance of oxidative triggers, mandatory pre-treatment screening in at-risk populations, and immediate discontinuation of offending agents if hemolysis occurs. 1, 2

Pre-Treatment Screening

Screen all patients of Mediterranean, African, Indian, or Southeast Asian descent before prescribing any oxidant drugs. 1, 2, 3

Testing Approach

• Qualitative fluorescent spot tests are sufficient for detecting severe deficiency (<10% enzyme activity) in males and homozygous females 3
• Quantitative G6PD assays are required for:
  • Heterozygous females (who may have variable enzyme levels due to X-inactivation) 3
  • Patients being considered for tafenoquine (requires >70% activity) 3
  • Borderline cases where degree of deficiency determines treatment decisions 1, 3

Critical Timing Pitfalls

• Never test during or immediately after acute hemolysis - reticulocytes contain near-normal enzyme levels and will mask deficiency 3
• Wait at least 50 days post-transfusion before enzyme testing (ideally 120 days), as 6-12% donor RBC contamination causes false-negatives 3
• Remove buffy coat or use filtration before testing - whole blood with white cells prevents accurate detection 3

Absolute Contraindications (High-Risk Oxidants)

These medications must never be given to G6PD-deficient patients:

• Primaquine - causes severe hemolytic anemia and is FDA-contraindicated in severe G6PD deficiency 2, 4
• Dapsone - potent oxidant causing methemoglobinemia and hemolysis 1, 2
• Methylene blue - causes severe hemolytic anemia and is contraindicated 1, 2
• Rasburicase - absolutely contraindicated 3

Variant-Specific Risk Stratification

• Mediterranean variant (Gdmed): Life-threatening hemolysis requiring absolute avoidance of all oxidants 1, 2, 3
• African variant (GdA-): Milder, self-limited hemolysis but still requires oxidant avoidance 1, 2

Medium-Risk Medications (Use with Extreme Caution)

• Sulfonamides (including sulfamethoxazole/cotrimoxazole): Recent data suggests safer than historically believed, but caution still warranted 2
• Local anesthetics (benzocaine, prilocaine, lidocaine, tetracaine): Can precipitate methemoglobinemia 2
• Chloroquine/Hydroxychloroquine: Relatively safe at standard doses in most G6PD-deficient patients 1

Safe Alternatives

For Pneumocystis Prophylaxis

• Atovaquone or inhaled pentamidine instead of dapsone 3

For Dermatologic Conditions

• Mycophenolate, azathioprine, or methotrexate instead of dapsone 3

For Anesthesia/Analgesia

• Benzodiazepines, codeine/codeine derivatives, propofol, fentanyl, and ketamine have not been shown to cause hemolytic crises 5

Management of Acute Hemolytic Crisis

Recognition

• Darkening of urine (hemoglobinuria) 4
• Marked fall in hemoglobin or erythrocyte count 4
• Elevated indirect bilirubin 6

Immediate Actions

1. Discontinue the offending oxidant immediately 3, 4
2. Check baseline hemoglobin/hematocrit and monitor closely (days 3 and 8) 4
3. Admit for observation - adequate medical support must be available 4, 5

Treatment of Methemoglobinemia

• Ascorbic acid (Vitamin C) is the treatment of choice when methylene blue is contraindicated 2, 3
• Dosing: 0.2-1.0 g/day orally in divided doses 2
• Monitor for rebound methemoglobinemia requiring repeat dosing every 6-8 hours for up to 2-3 days after dapsone exposure 3

Severe Hemolysis

• Consider exchange transfusion for life-threatening cases 3
• Plasmapheresis may be effective when the trigger agent is unknown and hemolysis is severe 6

Special Populations

Pregnancy

• Primaquine is absolutely contraindicated in pregnancy - even if the mother is G6PD-normal, the fetus may be deficient 4
• Pregnancy testing required before starting primaquine in sexually-active females of reproductive potential 4
• Contraception advised during treatment with high-risk oxidants 4

Neonates

• Screen for G6PD deficiency in high-risk populations to prevent kernicterus from neonatal jaundice 7, 8
• Phototherapy is effective and suitable for primary care settings 8

Family Screening

Screen first-degree relatives of G6PD-deficient patients, as this is an X-linked disorder 3, 9

Patient Education

Inform patients of:

• Signs and symptoms of acute hemolytic crisis (dark urine, jaundice, fatigue, shortness of breath) 5
• Need to avoid fava beans 5, 7
• Importance of informing all healthcare providers of their G6PD status 5
• Infections and metabolic stress can also trigger hemolysis 5, 7