Hematology · Hemolytic Anemia
The facts most likely to be tested
G6PD deficiency is an X-linked recessive disorder that leads to episodic hemolytic anemia due to an inability to maintain reduced glutathione levels.
Patients typically present with acute hemolysis following exposure to oxidative stressors such as fava beans, dapsone, primaquine, or sulfonamides.
Peripheral blood smears during an acute hemolytic episode reveal bite cells (degmacytes) and blister cells.
The supravital stain (e.g., crystal violet) is used to visualize Heinz bodies, which are denatured, precipitated hemoglobin inclusions within erythrocytes.
G6PD enzyme activity levels may be falsely normal during an acute hemolytic episode because the most enzyme-deficient cells have already been destroyed.
The pathophysiology involves a failure of the hexose monophosphate shunt to generate NADPH, leaving red blood cells vulnerable to oxidative injury.
Management focuses on the discontinuation of the offending agent and supportive care, as the condition is generally self-limiting once the oxidative stress is removed.
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A 24-year-old male presents to the emergency department with dark-colored urine and fatigue that began 24 hours after starting a new medication for a skin condition. Physical examination reveals scleral icterus and pallor. Laboratory studies show a hemoglobin of 8.2 g/dL, an elevated reticulocyte count, and indirect hyperbilirubinemia. A peripheral blood smear demonstrates the presence of bite cells.
What is the most likely diagnosis?
G6PD deficiency
The patient's presentation of acute hemolysis following medication exposure, combined with the classic finding of bite cells on peripheral smear, is pathognomonic for G6PD deficiency.
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Etiology / Epidemiology
X-linked recessive disorder common in African, Mediterranean, and Asian males.
Clinical Manifestations
Episodic hemolytic anemia triggered by oxidative stress; bite cells and blister cells.
Diagnosis
G6PD enzyme assay is the gold standard; perform after the acute hemolytic episode.
Treatment
Avoidance of oxidative triggers; do not test during acute hemolysis.
Prognosis
Generally excellent with trigger avoidance; rare risk of acute kidney injury.
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Epidemiology & Etiology
This is an X-linked recessive trait providing a survival advantage against Plasmodium falciparum malaria. It is most prevalent in populations of African, Mediterranean, and Southeast Asian descent. The deficiency results in an inability to maintain adequate levels of NADPH during oxidative stress.
Pertinent Anatomy
The defect resides within the erythrocyte membrane and cytoplasm. Because mature red blood cells lack a nucleus and mitochondria, they cannot synthesize new enzymes to replace the deficient G6PD.
Pathophysiology
G6PD is essential for the pentose phosphate pathway, which generates NADPH to keep glutathione in a reduced state. Without reduced glutathione, oxidative stress causes hemoglobin to denature and precipitate into Heinz bodies. These inclusions are removed by splenic macrophages, resulting in the characteristic bite cells.
Clinical Manifestations
Patients typically present with sudden onset of jaundice, dark urine, and pallor following exposure to oxidative triggers. Look for Heinz bodies on peripheral smear and acute hemolytic crisis symptoms. Common triggers include fava beans, infections, and specific medications.
Diagnosis
The G6PD enzyme assay is the definitive diagnostic test. Do not perform during an acute episode as the older, enzyme-deficient cells may have already lysed, leading to a false-negative result. Wait 6–8 weeks post-hemolysis for accurate testing.
Treatment
Management is primarily supportive and focused on trigger avoidance. Avoid sulfonamides, nitrofurantoin, primaquine, and fava beans during active disease. In severe cases, blood transfusion may be required for symptomatic anemia.
Prognosis
Prognosis is excellent if the patient avoids known oxidative stressors. The primary long-term complication is chronic hemolysis in rare variants, though most patients remain asymptomatic between episodes. Monitor for hemoglobinuria which can lead to renal failure.
Differential Diagnosis
Autoimmune Hemolytic Anemia: positive Coombs test
Hereditary Spherocytosis: increased MCHC and negative Coombs
Sickle Cell Disease: presence of sickled cells on smear
Thalassemia: microcytic anemia with target cells
Pyruvate Kinase Deficiency: chronic hemolysis without Heinz bodies