In a 29‑year‑old African‑American male with no transfusion or medical history, how should a quantitative glucose‑6‑phosphate dehydrogenase (G6PD) activity of 3.9 U/g hemoglobin (reference 7.0–20.5) be interpreted and what drug precautions and further testing are recommended?

Interpretation and Management of G6PD Activity of 3.9 U/g Hemoglobin in a 29-Year-Old African American Male

This patient has severe G6PD deficiency (19% of normal activity) and must strictly avoid all oxidant drugs including dapsone, primaquine, tafenoquine, rasburicase, methylene blue, and sulfonamides. 1

Calculating Percentage of Normal Activity

Divide the patient's G6PD value (3.9) by the laboratory's upper limit of normal (20.5) and multiply by 100, yielding 19% of normal activity—this percentage determines medication safety and hemolysis risk. 1

• Values <30% of normal indicate severe deficiency, placing this patient in the highest-risk category for oxidant drug-induced hemolysis. 1
• The African variant (GdA-) is found in 10–15% of Black men and typically causes milder, self-limited hemolysis compared to the Mediterranean variant (Gdmed), which can be life-threatening. 2, 3

Absolutely Contraindicated Medications

The following seven medications are definitively contraindicated and must never be prescribed:

• Primaquine – contraindicated in severe G6PD deficiency (<30% activity); only patients with 30–70% activity and non-Mediterranean variants may receive modified weekly dosing (45 mg once weekly for 8 weeks) with close hematological monitoring. 1, 3, 4
• Tafenoquine – requires G6PD activity ≥70% for safe use; this patient is ineligible. 1
• Dapsone – potent oxidant causing methemoglobinemia and hemolysis. 1, 5, 3
• Rasburicase – causes severe hemolytic anemia. 1, 5
• Methylene blue (methylthioninium chloride) – contraindicated; use ascorbic acid instead for methemoglobinemia. 1, 5, 3
• Sulfonamides (including co-trimoxazole) – can trigger hemolysis. 2
• Aspirin – explicitly contraindicated due to overwhelming reduced antioxidant capacity. 5

Medications Requiring Caution

• NSAIDs (ibuprofen, diclofenac) present moderate hemolysis risk; monitor hemoglobin closely if use is unavoidable. 5, 6
• Chloroquine/hydroxychloroquine in standard doses appear relatively safe in most G6PD-deficient patients, but vigilance is warranted. 3
• Penicillins (amoxicillin) are not contraindicated and can be used in normal therapeutic doses. 5

Critical Testing Considerations and Pitfalls

This quantitative result is reliable only if the following conditions were met:

• Testing was NOT performed during or immediately after acute hemolysis, as reticulocytes and young RBCs contain near-normal enzyme levels that mask deficiency. 1
• No RBC transfusion occurred within 50–120 days prior to testing, as donor cells (6–12% contamination) produce false-negative results. 1
• Proper sample preparation with buffy coat removal or filtration was performed; whole blood without white cell removal prevents accurate detection. 1

If any of these conditions are uncertain, repeat quantitative testing under optimal conditions is mandatory before making medication decisions. 1

Recommended Further Testing

• Genetic testing to identify the specific G6PD variant (African GdA- versus Mediterranean Gdmed) determines hemolytic risk severity and guides management decisions, particularly if borderline enzyme activity (30–70%) is encountered in future family screening. 1, 5
• Screen first-degree relatives, as this is an X-linked disorder; female relatives may be heterozygous carriers with intermediate deficiency. 1

Monitoring for Hemolytic Crisis

Educate the patient to seek immediate medical attention if the following occur after starting any new medication or during infection:

• Darkening of urine (hemoglobinuria) – typically appears 24–72 hours after oxidant exposure. 4, 6
• Jaundice – present in 87.8% of hemolytic crises. 6
• Pallor and fatigue – universal in acute hemolysis. 6

If hemolysis occurs:

• Immediately discontinue the offending agent. 4
• Check baseline hemoglobin and hematocrit, then monitor closely (e.g., day 3 and 8). 4
• Consider transfusion if hemoglobin drops below 7–8 g/dL with symptoms. 5
• Provide folic acid supplementation (1 mg daily) during and after hemolytic episodes. 5

Alternative Therapies for Common Indications

• For Pneumocystis prophylaxis (if HIV-positive or immunosuppressed): use atovaquone or inhaled pentamidine instead of dapsone/co-trimoxazole. 1
• For dermatologic conditions requiring dapsone: substitute mycophenolate, azathioprine, or methotrexate. 1
• For malaria treatment: artemisinin-based combination therapies (artesunate, artemether-lumefantrine, dihydroartemisinin-piperaquine) are safe. 3

Common Pitfalls to Avoid

• Never rely on qualitative spot tests for medication decision-making; quantitative assays are essential for accurate risk stratification. 1
• Never assume historical G6PD results are valid if timing, transfusion history, or reticulocyte count are unknown. 1
• Never test during acute hemolytic crisis, as false-elevated activity leads to inappropriate clinical decisions. 1
• Recognize that infections (pneumonia, tonsillitis, typhoid, hepatitis A, UTI) are the second most common hemolysis trigger after dietary oxidants (fava beans, falafel, chickpeas). 6