How should a patient with the Mediterranean variant of glucose‑6‑phosphate dehydrogenase deficiency be managed, including drugs and foods to avoid and treatment of hemolytic episodes?

Management of G6PD Mediterranean Deficiency

Critical Risk Profile

The Mediterranean variant (G6PD-B⁻) carries a very high risk of severe, potentially life-threatening hemolysis and requires strict avoidance of all oxidant medications, unlike the milder African variant. 1, 2

• This variant results from a single C→T transition at nucleotide 563, causing a serine-to-phenylalanine substitution that severely decreases enzyme stability and catalytic efficiency 3, 4
• Patients of Mediterranean, Middle Eastern, Indian, or Southeast Asian descent warrant high clinical suspicion 5

Absolutely Contraindicated Medications

High-Risk Oxidants

• Dapsone: Potent oxidant causing methemoglobinemia and severe hemolysis; absolutely avoid 2
• Methylene blue (methylthioninium chloride): Causes severe hemolytic anemia; contraindicated 2
• Primaquine: Contraindicated in severe deficiency; if radical cure of P. vivax/P. ovale is essential and G6PD activity is 30-70%, use only 45 mg weekly for 8 weeks with intensive monitoring 2
• Tafenoquine: Contraindicated when G6PD activity <70% 2
• Rasburicase: Absolutely contraindicated 5

Other Hemolytic Agents

• NSAIDs: Diclofenac sodium, ibuprofen, and aspirin can trigger hemolysis 5
• Fava beans: Classic trigger for favism in Mediterranean variant 6

Safe Antimalarial Alternatives

• Artemisinin-based combination therapies (ACTs) including artesunate, artemether-lumefantrine, and dihydroartemisinin-piperaquine are safe for malaria treatment 2
• Chloroquine and hydroxychloroquine at standard doses are relatively safe in most G6PD-deficient patients 2

Mandatory Screening Protocol

Screen for G6PD deficiency before starting any oxidant drug, particularly in patients of Mediterranean, African, Middle Eastern, Indian, or Southeast Asian ancestry. 1, 5

• Use qualitative screening for initial assessment 1
• Quantitative G6PD testing is required before tafenoquine and for borderline cases 1, 2
• Avoid testing during acute hemolytic crisis as G6PD levels can be falsely elevated; repeat testing 3 months after crisis for accurate diagnosis 5

Recognition of Hemolytic Crisis

Classic Triad (24-72 hours post-exposure)

• Pallor 5
• Dark red/brown urine (hemoglobinuria without RBCs on microscopy) 5
• Jaundice 5

Additional Warning Signs

• Back or abdominal pain 1
• Sudden fatigue 2

Immediately discontinue any potentially hemolytic medication if these signs occur. 1

Acute Hemolytic Crisis Management

Immediate Supportive Care

• Aggressive intravenous hydration to maintain renal perfusion and prevent hemoglobin-induced acute kidney injury 2
• Target urine output ≥100 mL/hour in adults (≥3 mL/kg/hour for patients <40 kg) 2
• Monitor vital signs every 4-6 hours during initial 24-48 hours to detect tachycardia or hypotension 2

Transfusion Thresholds

• Transfuse when hemoglobin falls below 7 g/dL 2
• Transfuse at any hemoglobin level if patient develops: dyspnea, chest pain, altered mental status, or hemodynamic instability 2
• If hemoglobin ≈8.6 g/dL and patient is asymptomatic, transfusion is not indicated; use supportive care and close observation 2
• Consider discontinuing hemolysis-inducing drugs when hemoglobin drops below 8.5 g/dL 2

Renal Monitoring

• Continuously monitor for acute kidney injury from hemoglobinuria 2
• Maintain aggressive hydration throughout crisis 2

Family Screening

• Test first-degree relatives of affected patients for G6PD deficiency 1
• Female carriers may have variable expression due to X-chromosome inactivation 4

Dietary Restrictions

• Strictly avoid fava beans (broad beans), which are strongly associated with favism in the Mediterranean variant 6
• No consensus exists on restricting other specific foods beyond fava beans 5