PNH301 TesT 2 – AcTuAl exAm 2026/2027 – comPleTe
exAm-sTyle QuesTioNs wiTH DeTAileD RATioNAles | 100%
VeRifieD | PAss GuARANTeeD – A+ GRADeD
**Topic:** Paroxysmal Nocturnal Hemoglobinuria (PNH) – Pathophysiology, Clinical Manifestations, Diagnosis, and
Management
Question 1
What is the underlying molecular defect in Paroxysmal Nocturnal Hemoglobinuria (PNH)?
A. A mutation in the beta-globin gene leading to sickle cell disease
B. A somatic mutation in the PIG-A gene on the X chromosome
C. An autosomal dominant mutation in the complement factor H gene
D. A deficiency of vitamin B12 due to autoimmune gastritis
Correct Answer: B
Rationale: PNH is caused by an acquired somatic mutation in the phosphatidylinositol glycan class A (PIG-A) gene.
This mutation leads to a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins, including CD55 and
CD59, which protect blood cells from complement-mediated lysis.
---
Question 2
Which of the following laboratory findings is the most specific diagnostic test for PNH?
A. Direct Coombs test
B. Serum haptoglobin level
C. Flow cytometry for CD55 and CD59 on red blood cells and granulocytes
D. Hemoglobin electrophoresis
Correct Answer: C
, Rationale: Flow cytometry is the gold standard for diagnosing PNH. It detects the absence or deficiency of GPI-
linked proteins (CD55 and CD59) on various blood cell lineages. The direct Coombs test is positive in autoimmune
hemolytic anemia, not PNH.
---
Question 3
A patient with PNH experiences dark urine that is most noticeable in the morning. What is the primary reason for
this pattern?
A. Increased hemolysis during sleep due to mild respiratory acidosis and decreased pH
B. Nocturnal production of bilirubin by the liver
C. Morning dehydration concentrating the urine
D. Diurnal variation in renal filtration rate
Correct Answer: A
Rationale: The classic “paroxysmal nocturnal” hemoglobinuria occurs because during sleep, mild hypoventilation
leads to a drop in blood pH (respiratory acidosis). The acidic environment enhances complement activation,
increasing hemolysis of complement-sensitive PNH red cells, and hemoglobinuria is most evident upon waking.
---
Question 4
Which two GPI-anchored proteins are most critical for protecting erythrocytes from complement-mediated lysis?
A. CD4 and CD8
B. CD55 (decay-accelerating factor) and CD59 (membrane inhibitor of reactive lysis)
C. CD34 and CD45
D. CD3 and CD19
Correct Answer: B
Rationale: CD55 accelerates the decay of C3 convertase, while CD59 prevents formation of the membrane attack
complex (C5b-9). Their absence on PNH red cells makes them susceptible to complement‑induced intravascular
hemolysis.
exAm-sTyle QuesTioNs wiTH DeTAileD RATioNAles | 100%
VeRifieD | PAss GuARANTeeD – A+ GRADeD
**Topic:** Paroxysmal Nocturnal Hemoglobinuria (PNH) – Pathophysiology, Clinical Manifestations, Diagnosis, and
Management
Question 1
What is the underlying molecular defect in Paroxysmal Nocturnal Hemoglobinuria (PNH)?
A. A mutation in the beta-globin gene leading to sickle cell disease
B. A somatic mutation in the PIG-A gene on the X chromosome
C. An autosomal dominant mutation in the complement factor H gene
D. A deficiency of vitamin B12 due to autoimmune gastritis
Correct Answer: B
Rationale: PNH is caused by an acquired somatic mutation in the phosphatidylinositol glycan class A (PIG-A) gene.
This mutation leads to a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins, including CD55 and
CD59, which protect blood cells from complement-mediated lysis.
---
Question 2
Which of the following laboratory findings is the most specific diagnostic test for PNH?
A. Direct Coombs test
B. Serum haptoglobin level
C. Flow cytometry for CD55 and CD59 on red blood cells and granulocytes
D. Hemoglobin electrophoresis
Correct Answer: C
, Rationale: Flow cytometry is the gold standard for diagnosing PNH. It detects the absence or deficiency of GPI-
linked proteins (CD55 and CD59) on various blood cell lineages. The direct Coombs test is positive in autoimmune
hemolytic anemia, not PNH.
---
Question 3
A patient with PNH experiences dark urine that is most noticeable in the morning. What is the primary reason for
this pattern?
A. Increased hemolysis during sleep due to mild respiratory acidosis and decreased pH
B. Nocturnal production of bilirubin by the liver
C. Morning dehydration concentrating the urine
D. Diurnal variation in renal filtration rate
Correct Answer: A
Rationale: The classic “paroxysmal nocturnal” hemoglobinuria occurs because during sleep, mild hypoventilation
leads to a drop in blood pH (respiratory acidosis). The acidic environment enhances complement activation,
increasing hemolysis of complement-sensitive PNH red cells, and hemoglobinuria is most evident upon waking.
---
Question 4
Which two GPI-anchored proteins are most critical for protecting erythrocytes from complement-mediated lysis?
A. CD4 and CD8
B. CD55 (decay-accelerating factor) and CD59 (membrane inhibitor of reactive lysis)
C. CD34 and CD45
D. CD3 and CD19
Correct Answer: B
Rationale: CD55 accelerates the decay of C3 convertase, while CD59 prevents formation of the membrane attack
complex (C5b-9). Their absence on PNH red cells makes them susceptible to complement‑induced intravascular
hemolysis.
