📘 Internal Medicine Quiz Community
📝 History
- 35-year-old male
- Recurrent dark-colored urine, especially morning
- Fatigue and weakness
- Mild jaundice
- Painful swelling of left leg for 2 weeks
- No trauma, malignancy or immobilization history
🩺 Examination
- Pallor
- Mild icterus
- Left calf swollen, warm, red and tender
- Positive Homan sign
- Mild splenomegaly
- Dark cola-colored urine
🔬 Investigations
- Hb: 7.8 g/dL ↓
- WBC: 3200/mm³ ↓
- Platelets: 90,000/mm³ ↓
- Reticulocyte count: 10% ↑
- LDH markedly elevated ↑
- Indirect bilirubin elevated ↑
- Direct Coombs test negative
- Urine hemosiderin positive
- Doppler: Left popliteal DVT
- D-dimer elevated
- PT/APTT normal
❓MCQ Question
What is the most likely diagnosis?
A. Autoimmune Hemolytic Anemia with thrombophilia
B. Paroxysmal Nocturnal Hemoglobinuria (PNH)
C. G6PD Deficiency with venous thrombosis
D. Antiphospholipid Antibody Syndrome
📋 Brief Case Summary
A middle-aged man presents with chronic intravascular hemolysis, morning hemoglobinuria, pancytopenia, elevated LDH, negative Coombs test, positive urine hemosiderin and unexplained venous thrombosis.
✅ Click to Reveal Answer
Show Answer
Answer: B. Paroxysmal Nocturnal Hemoglobinuria (PNH)
📚 Answer Explanation
PNH is an acquired clonal stem-cell disorder caused by mutation of the PIGA gene resulting in deficiency of GPI-anchored proteins (CD55 and CD59). Loss of complement regulation causes chronic intravascular hemolysis.
Classic features:
- Dark morning urine (hemoglobinuria)
- Coombs-negative hemolytic anemia
- Pancytopenia
- Venous thrombosis (especially unusual sites)
- Elevated LDH
- Positive urine hemosiderin
❌ Why Not the Other Options?
- A. Autoimmune Hemolytic Anemia: Usually Coombs positive.
- C. G6PD Deficiency: Episodic hemolysis after oxidative stress; thrombosis uncommon.
- D. Antiphospholipid Syndrome: Causes thrombosis but not chronic intravascular hemolysis with hemosiderinuria.
🩺 Five Brief Case Scenarios
- Young adult with morning hemoglobinuria and pancytopenia → PNH.
- Hepatic vein thrombosis with hemolytic anemia → PNH.
- Recurrent abdominal pain and dark urine → PNH.
- Coombs-negative hemolysis with thrombosis → PNH.
- Aplastic anemia evolving into hemolysis → PNH.
🧬 Simplified Pathophysiology
- PIGA mutation in hematopoietic stem cell.
- Loss of CD55 and CD59.
- Uncontrolled complement activation.
- Red cell destruction inside blood vessels.
- Free hemoglobin scavenges nitric oxide.
- Leads to thrombosis and smooth muscle dysfunction.
🩺 Physical Examination Pearls
- Pallor due to anemia.
- Mild jaundice due to hemolysis.
- Signs of DVT should be actively sought.
- Assess hepatosplenomegaly.
- Look for evidence of pancytopenia.
🔍 Investigations: Choosing Wisely
- Flow cytometry for CD55/CD59 deficiency (gold standard).
- FLAER assay confirms diagnosis.
- CBC for pancytopenia.
- LDH and bilirubin for hemolysis.
- Doppler study for thrombosis.
- Bone marrow examination when indicated.
💊 Management
- Eculizumab or Ravulizumab.
- Anticoagulation for thrombosis.
- Folate supplementation.
- Blood transfusion if needed.
- Treat iron deficiency.
- Stem cell transplantation in selected severe cases.
📑 Differential Diagnosis
- Autoimmune hemolytic anemia
- G6PD deficiency
- Microangiopathic hemolytic anemia
- Aplastic anemia
- Antiphospholipid syndrome
- Hereditary spherocytosis
⚠️ Clinical Pitfalls
- Missing diagnosis because hemoglobinuria is intermittent.
- Ignoring thrombosis in unusual sites.
- Assuming all hemolytic anemia is Coombs positive.
- Failure to perform flow cytometry.
- Overlooking associated bone marrow failure.
💎 Clinical Pearls
- PNH = Hemolysis + Pancytopenia + Thrombosis.
- Most feared complication is thrombosis.
- Coombs test is negative.
- LDH is often markedly elevated.
- Flow cytometry is diagnostic.
📅 Monitoring & Follow-Up
- Regular CBC monitoring.
- LDH trend assessment.
- Monitor thrombosis recurrence.
- Assess renal function.
- Evaluate response to complement inhibitors.
- Annual bone marrow assessment if indicated.
❓FAQ (Questions & Answers)
- What causes PNH?
PIGA gene mutation. - Why is urine dark in the morning?
Overnight hemoglobin accumulation. - Why is Coombs test negative?
Hemolysis is complement mediated, not antibody mediated. - What is the gold standard test?
Flow cytometry with FLAER. - Why does thrombosis occur?
Nitric oxide depletion and complement activation. - What is the most serious complication?
Venous thrombosis. - Which veins are commonly involved?
Hepatic, portal, cerebral and deep veins. - Can PNH cause pancytopenia?
Yes. - What is hemosiderinuria?
Urinary iron loss from chronic hemolysis. - Can PNH progress to aplastic anemia?
Yes. - What is eculizumab?
A monoclonal antibody against C5. - What is ravulizumab?
Long-acting complement inhibitor. - Can PNH be cured?
Stem cell transplantation may be curative. - Why is LDH elevated?
Reflects intravascular hemolysis. - What follow-up is needed?
CBC, LDH, thrombosis surveillance and renal monitoring.
📖 Key Guidelines & References
- British Society for Haematology Guidelines on PNH
- International PNH Interest Group Recommendations
- ASH Guidelines for Hemolytic Disorders
- Harrison's Principles of Internal Medicine
- Oxford Handbook of Clinical Haematology
- UpToDate: Paroxysmal Nocturnal Hemoglobinuria
- WHO Classification of Hematolymphoid Tumors
🔎Keywords
PNH MCQ, Paroxysmal Nocturnal Hemoglobinuria Quiz, PNH Clinical Case, Hemolytic Anemia MCQ, Dark Urine Diagnosis, Coombs Negative Hemolysis, PNH Flow Cytometry, PNH with DVT, Internal Medicine Quiz, Hematology Case Challenge
Tags:
Hematology