Introduction
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells (RBCs) worldwide, affecting over 400 million people. It is inherited in an X-linked recessive manner and is particularly prevalent in malaria-endemic regions. While many individuals remain asymptomatic throughout life, exposure to oxidative stress—often triggered by infections, certain drugs, or foods—can precipitate acute hemolysis.
This article discusses a classic presentation of acute hemolytic anemia in a G6PD-deficient patient following empirical therapy for a febrile illness, highlighting the clinical features, pathophysiology, diagnosis, and management.
Case Presentation
A 28-year-old male presented to the emergency department with a two-day history of high-grade fever accompanied by chills and rigors. He had no known comorbidities and no prior history of similar episodes. On examination, he was febrile (101.8°F), with stable hemodynamic parameters. Systemic examination was unremarkable.
Based on clinical suspicion of a febrile illness—possibly malaria, typhoid, or viral infection—he was empirically started on antipyretics and antibiotics, including ceftriaxone and an antimalarial (possibly primaquine or sulfonamide-based medication).
Within 24 hours of initiating treatment, he reported passing dark brown, tea-colored urine and began to feel fatigued and mildly short of breath. There was no history of trauma, vigorous exercise, or known ingestion of fava beans.
Clinical Suspicion
The sudden onset of dark-colored urine in a patient with known G6PD deficiency raised suspicion for acute intravascular hemolysis. The clinical picture suggested drug-induced oxidative stress leading to red blood cell destruction.
Pathophysiology
G6PD plays a critical role in the pentose phosphate pathway, helping generate NADPH, which in turn maintains the integrity of RBC membranes by reducing glutathione. In G6PD deficiency, RBCs are more vulnerable to oxidative damage.
Oxidative stress from:
- Infections (e.g., viral or bacterial)
- Medications like sulfonamides, nitrofurantoin, primaquine, dapsone, quinolones, and even high-dose paracetamol
- Foods such as fava beans
…can lead to the rapid breakdown of RBCs (hemolysis), releasing free hemoglobin into the circulation, part of which is excreted in urine, causing the characteristic dark discoloration.
Clinical Features of Hemolysis in G6PD Deficiency
- Sudden onset fatigue and pallor
- Jaundice (due to unconjugated hyperbilirubinemia)
- Dark-colored urine (hemoglobinuria)
- Mild to moderate splenomegaly
- Back or abdominal pain (due to hemolysis)
- Laboratory findings:
- Anemia with falling hemoglobin
- Elevated LDH
- Elevated indirect bilirubin
- Decreased haptoglobin
- Reticulocytosis
- Peripheral smear may show “bite cells” and “blister cells”
Diagnosis
- Urinalysis: Positive for hemoglobin but negative for RBCs (indicating hemoglobinuria, not hematuria)
- Complete blood count: Normocytic normochromic anemia
- Peripheral smear: Features of hemolysis (schistocytes, bite cells)
- G6PD assay: Enzyme activity measured after recovery phase (may be falsely normal during acute hemolysis due to younger RBCs having higher G6PD activity)
- Coombs test: Negative (rules out autoimmune hemolytic anemia)
Differential Diagnosis
- Hemoglobinuria due to rhabdomyolysis (check serum CPK)
- Autoimmune hemolytic anemia
- Hemolysis due to other causes (e.g., microangiopathic hemolytic anemia)
- Malaria-induced hemolysis
Management
Immediate Management
- Discontinue the offending drug(s) immediately
- Supportive care: Hydration to maintain renal perfusion and prevent acute tubular necrosis
- Monitor hemoglobin, renal function, and urine output
- In severe cases:
- Transfusion of packed RBCs
- Dialysis if acute kidney injury develops
Long-term Care
- Patient education:
- Avoid known oxidative drugs (sulfonamides, nitrofurantoin, antimalarials like primaquine)
- Avoid fava beans
- Inform healthcare providers about G6PD status before starting new medications
Prognosis
With prompt identification and withdrawal of the precipitating agent, most cases recover fully without long-term complications. However, recurrent episodes or delayed recognition may result in acute kidney injury or severe anemia.
Conclusion
G6PD deficiency, although often benign, can manifest with life-threatening hemolysis when triggered by infections or certain medications. Clinicians must be vigilant when prescribing empirical treatments for febrile illnesses in patients with known or suspected G6PD deficiency. Early recognition of dark-colored urine as a sign of hemolysis and timely withdrawal of the offending agent are critical steps in patient management.
Key Takeaways
- Always consider G6PD status in patients from high-risk ethnic backgrounds or with a history of hemolysis.
- In G6PD-deficient individuals, fever and dark urine following treatment suggest oxidative hemolysis.
- Avoid prescribing high-risk medications unless absolutely necessary.
- Patient education and medical alert identification are vital for preventing recurrence.
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