In a G6PD‑deficient patient who stopped primaquine after developing hemolytic anemia with jaundice and a hemoglobin of 8.6 g/dL but no symptoms, what is the appropriate management?

Management of Primaquine-Induced Hemolytic Anemia in G6PD Deficiency

In this G6PD-deficient patient with primaquine-induced hemolysis (Hb 8.6 g/dL) who is now asymptomatic after drug discontinuation, provide supportive care with aggressive IV hydration, monitor hemoglobin every 6-12 hours initially, watch closely for acute kidney injury from hemoglobinuria, and transfuse only if hemoglobin drops below 7 g/dL or symptoms develop. 1, 2

Immediate Management

Discontinuation and Monitoring

• Primaquine has been correctly discontinued – this is the most critical first step, as the FDA label explicitly states to "discontinue the use of primaquine phosphate promptly if signs suggestive of hemolytic anemia occur (darkening of the urine, marked fall of hemoglobin or erythrocytic count)." 2

• Intensive hematological monitoring is required: Check hemoglobin, hematocrit, and reticulocyte count every 6-12 hours for the first 24-48 hours, then daily until stabilization. 1, 2

• Monitor for signs of ongoing hemolysis: dark urine (hemoglobinuria), jaundice progression, abdominal or back pain, and sudden worsening of fatigue or pallor. 1

Renal Protection

• Provide aggressive intravenous hydration to maintain urine output and prevent hemoglobin-induced acute kidney injury – this is critical as hemoglobinuria can cause acute tubular necrosis. 1

• Monitor renal function closely with serial creatinine, BUN, and urine output measurements, as acute kidney injury is a well-recognized complication of primaquine-induced hemolysis. 1, 3

• Maintain urine output at least 100 mL/hour in adults (or 3 mL/kg/hour if body weight <40 kg). 4

Transfusion Threshold

When to Transfuse

• At Hb 8.6 g/dL without symptoms, transfusion is NOT indicated – observe closely with supportive care only. 4

• Consider transfusion if hemoglobin drops below 7 g/dL, or if the patient develops symptoms of severe anemia (dyspnea, chest pain, altered mental status, hemodynamic instability) regardless of absolute hemoglobin level. 4

• The Korean Association for the Study of the Liver recommends considering ribavirin discontinuation at Hb <8.5 g/dL for drug-induced anemia, which provides a reasonable threshold for intervention in this context. 4

Monitoring Parameters

Laboratory Surveillance

• Complete blood count with differential: Every 6-12 hours initially, then daily until hemoglobin stabilizes and begins to rise. 1, 2

• Renal function tests (creatinine, BUN): Daily monitoring for acute kidney injury. 1

• Reticulocyte count: To assess bone marrow response and predict recovery trajectory. 5

• Bilirubin and LDH: To quantify degree of hemolysis and monitor resolution. 5

• Urinalysis: To detect hemoglobinuria and monitor for resolution. 1, 3

Clinical Surveillance

• Vital signs every 4-6 hours initially, watching for tachycardia or hypotension. 4

• Urine color and output monitoring – darkening suggests ongoing hemolysis. 1, 2

• Assess for symptoms: fatigue, dyspnea, chest pain, back pain, or altered mental status. 1, 5

Expected Clinical Course

Hemolysis Dynamics

• Hemolysis in G6PD deficiency is typically self-limited once the oxidant drug is stopped, as only older erythrocytes with lower G6PD activity are destroyed. 5, 6

• The nadir of hemoglobin typically occurs 7-10 days after primaquine exposure, so this patient may experience further decline before recovery begins. 6, 7

• Recovery begins when younger erythrocytes (with higher G6PD activity in the African variant, though this patient's variant is unknown) predominate. 5, 6

Specific Considerations

G6PD Variant Matters

• The Mediterranean G6PD variant (B⁻) carries very high risk of severe, life-threatening hemolysis, while the African variant (A⁻) typically causes milder, self-limited hemolysis. 4, 1

• If the patient's G6PD variant is unknown, assume Mediterranean variant and manage more conservatively given the presence of jaundice. 1

Supportive Medications

• Acetaminophen (paracetamol) is safe for symptomatic relief and may have renoprotective effects during oxidative hemolysis. 3

• Avoid other oxidant medications that could worsen hemolysis (dapsone, methylene blue, sulfonamides, nitrofurantoin). 1, 5

Future Malaria Treatment

Alternative Antimalarials

• Artemisinin-based combination therapies (ACTs) including artesunate, artemether-lumefantrine, and dihydroartemisinin-piperaquine can be used safely for malaria treatment in G6PD-deficient patients. 4, 1

• Chloroquine and hydroxychloroquine in standard doses are relatively safe in most G6PD-deficient patients. 4, 1

• Primaquine and tafenoquine remain contraindicated in severe G6PD deficiency; if radical cure is needed in the future, consider weekly primaquine 45 mg for 8 weeks only if G6PD activity is >30% and with close monitoring. 4, 1, 2

Common Pitfalls to Avoid

• Do not transfuse prematurely – at Hb 8.6 g/dL without symptoms, transfusion adds unnecessary risk and the hemolysis will self-limit. 4

• Do not underestimate renal risk – aggressive hydration is as important as monitoring hemoglobin. 1, 3

• Do not restart primaquine – even at reduced doses, this patient has demonstrated susceptibility to severe hemolysis. 2

• Do not assume hemolysis has peaked – the nadir may not occur for several more days after drug discontinuation. 6, 7