Hematology Oncology · Year 2 · from Hematology Oncology

Case 3: Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Patient Presentation

Demographics: 25-year-old African American male

Chief Complaint: Sudden onset of fatigue, dark urine, and yellowing eyes for 2 days

History of Present Illness: The patient was recently diagnosed with a urinary tract infection and started on trimethoprim-sulfamethoxazole 5 days ago. Two days ago, he noticed sudden fatigue, back pain, and passage of very dark urine. He has never had similar episodes. His family history is notable for a brother who had a "blood problem" after taking an antimalarial medication.

Physical Examination:

  • Vital signs: BP 105/60, HR 115, RR 22, Temp 37.8C
  • General: Pale, icteric, ill-appearing young man
  • HEENT: Scleral icterus, conjunctival pallor
  • Cardiac: Tachycardic, flow murmur
  • Abdomen: Mild splenomegaly
  • Skin: Jaundice

Workup and Results

Complete Blood Count:

  • Hemoglobin: 7.2 g/dL (was 14.5 g/dL baseline)
  • MCV: 95 fL (normal)
  • Reticulocyte count: 8% (elevated)
  • WBC: 14,200/uL (elevated)

Hemolysis Labs:

  • LDH: 1,250 U/L (markedly elevated)
  • Total bilirubin: 6.8 mg/dL
  • Indirect bilirubin: 6.1 mg/dL
  • Haptoglobin: < 10 mg/dL (undetectable)
  • Urinalysis: Hemoglobinuria present (intravascular hemolysis)

Peripheral Blood Smear:

  • Bite cells (degmacytes)
  • Blister cells
  • Polychromasia
  • Heinz bodies seen on supravital staining

Direct Antiglobulin Test: Negative

G6PD Level: 2.1 U/g Hb (low, normal 4.6-13.5) Note: May be falsely normal during acute episode due to young RBC predominance

Diagnosis

G6PD Deficiency with Acute Hemolytic Crisis (Drug-Induced)

Key diagnostic features:

  • Acute intravascular hemolysis following oxidant drug exposure
  • Bite cells and Heinz bodies characteristic of oxidant damage
  • Negative DAT excludes immune hemolysis
  • G6PD level low (confirm 2-3 months after acute episode)
  • X-linked inheritance pattern suggested by family history

Treatment Plan

  1. Immediate management:
  • Stop the offending drug (TMP-SMX)
  • IV fluid hydration to maintain urine output and prevent AKI
  • Transfusion if symptomatic or hemoglobin critically low
  • Alternative antibiotic for UTI (nitrofurantoin is also contraindicated)
  1. Prevention:
  • Provide patient with list of drugs and foods to avoid
  • Avoid: sulfonamides, dapsone, primaquine, nitrofurantoin, fava beans
  • Consider medical alert bracelet
  1. Follow-up:
  • Repeat G6PD level 2-3 months after acute episode
  • Genetic counseling for X-linked inheritance
  • Screen family members at risk

Teaching Points

  1. G6PD deficiency is the most common enzyme deficiency worldwide (X-linked)
  2. G6PD is needed to maintain glutathione in reduced form to protect against oxidant damage
  3. Oxidant stress (drugs, infection, fava beans) triggers acute hemolysis
  4. Bite cells form when Heinz bodies are "pitted out" by splenic macrophages
  5. G6PD level may be falsely normal during acute crisis (reticulocytes have higher G6PD)
  6. Repeat testing 2-3 months later when RBC population normalizes
  7. Hemolysis is self-limited as older, more deficient cells are destroyed first

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