Should I refer this 29-year-old African-American male with a low glucose-6-phosphate dehydrogenase activity (3.9 U/g Hb) measured two years ago, no transfusion or other medical history, to hematology or manage him in primary care?

Management of Confirmed G6PD Deficiency in Primary Care

You should manage this patient in primary care with focused education on trigger avoidance and documentation in the medical record—hematology referral is not necessary for an asymptomatic patient with confirmed G6PD deficiency. 1, 2

Understanding Your Patient's G6PD Status

Your patient has severe G6PD deficiency with activity of 3.9 U/g Hb, representing approximately 19% of normal activity (calculated as 3.9 ÷ 20.5 × 100). 2 This falls well below the 30% threshold that defines severe deficiency and mandates strict avoidance of oxidant drugs. 1, 2

• As an African-American male, he most likely carries the GdA- (African) variant, which typically causes milder, self-limited hemolysis compared to the Mediterranean variant (Gdmed) that can produce life-threatening hemolysis. 3, 1
• The African variant is found in 10-15% of Black men and women. 3
• Despite having the "milder" variant, his activity level of 19% still places him at significant risk for drug-induced hemolysis. 2

Primary Care Management Algorithm

Immediate Actions (Today's Visit)

1. Document G6PD deficiency prominently in the electronic health record with allergy alerts for contraindicated medications. 1, 2

2. Provide patient education on absolutely contraindicated medications: 3, 1, 2

• Dapsone (used for dermatologic conditions and Pneumocystis prophylaxis)
• Primaquine and tafenoquine (antimalarials for P. vivax/ovale radical cure)
• Methylene blue/methylthioninium chloride (used for methemoglobinemia)
• Rasburicase (used for tumor lysis syndrome)
• Sulfonamides (including trimethoprim-sulfamethoxazole in high doses)

3. Counsel on medium-risk medications that require caution: 3

• Chloroquine/hydroxychloroquine in standard doses appears relatively safe in most G6PD-deficient patients, but monitor for hemolysis. 3

4. Educate about non-pharmacologic triggers: 4

• Fava beans (broad beans) can trigger severe hemolysis and must be avoided
• Infections can occasionally trigger hemolysis through oxidative stress
• Naphthalene (mothballs) exposure should be avoided

No Repeat Testing Needed

Do not repeat G6PD testing unless there is uncertainty about the original result's validity. 2 The 2-year-old test is reliable because:

• He has never been transfused (transfusions can cause false-negative results for 50-120 days post-transfusion). 2
• The result is unambiguously low at 19% of normal activity. 2
• He was presumably not in acute hemolysis when tested (which could falsely elevate results due to young RBCs with higher enzyme activity). 2

When Hematology Referral IS Indicated

Refer to hematology only if: 1, 2

• He develops chronic hemolytic anemia (ongoing hemolysis without oxidant exposure)—this would suggest a rare sporadic G6PD mutation rather than the common polymorphic African variant. 4
• He experiences unexplained severe hemolysis despite trigger avoidance
• Genetic testing is needed to definitively identify the specific variant (e.g., if considering modified primaquine dosing for malaria prophylaxis, which requires knowing if he has the African vs. Mediterranean variant). 1, 2
• He requires a medication with uncertain G6PD safety profile and needs specialist risk-benefit assessment

Critical Prescribing Scenarios

If He Needs Pneumocystis Prophylaxis (HIV, Immunosuppression)

• Use atovaquone or inhaled pentamidine instead of trimethoprim-sulfamethoxazole. 2
• Dapsone is absolutely contraindicated at his activity level. 3, 2

If He Needs Malaria Prophylaxis or Treatment

• Artemisinin-based combination therapies (ACTs) including artesunate, artemether-lumefantrine, and dihydroartemisinin-piperaquine are safe for malaria treatment. 3
• Chloroquine may be used for prophylaxis with monitoring. 3
• Primaquine and tafenoquine are contraindicated at his 19% activity level (both require >30% activity for any consideration of use). 3, 1

If He Needs Dermatologic Immunosuppression

• Use mycophenolate, azathioprine, or methotrexate as alternatives to dapsone. 2

Common Pitfalls to Avoid

• Never assume G6PD deficiency is "mild" based solely on ethnicity—his 19% activity is severe regardless of variant type. 1, 2
• Never prescribe oxidant drugs during acute infections—the combined oxidative stress can precipitate severe hemolysis. 4
• Never rely on neutropenia as a screening marker—it may be present but is not reliable for G6PD deficiency. 1
• Screen first-degree relatives (brothers, sons, mother, sisters, daughters) as this is X-linked and family members may be affected. 2

Documentation Template for Your Note

Document the following to ensure safe prescribing across all providers:

• G6PD deficiency confirmed (3.9 U/g Hb, 19% of normal, tested [date])
• African-American male (likely GdA- variant)
• Absolute contraindications: dapsone, primaquine, tafenoquine, methylene blue, rasburicase
• Patient counseled on trigger avoidance including fava beans and oxidant drugs
• Allergy alerts entered in EHR for contraindicated medications