PNH301 – TEST 2 | 120 MULTIPLE-CHOICE
QUESTIONS | 2025/2026
(Complete practice exam with verified answers &
rationales)
Question 1: Which somatic mutation underlies the GPI-anchor deficiency in PNH?
A) JAK2 V617F
B) PIGA
C) CALR exon 9
D) BCR-ABL
Correct Answer: B) PIGA
Explanation: A mutation in the X-linked PIGA gene disrupts the first step of
glycosylphosphatidylinositol (GPI) anchor synthesis, yielding the PNH clone.
Question 2: The earliest, most sensitive screening test for a PNH clone in 2025 is:
A) Ham (acidified-serum) test
B) Sucrose-lysis test
C) FLAER-based high-sensitivity flow cytometry
D) Serum haptoglobin
Correct Answer: C) FLAER-based high-sensitivity flow cytometry
Explanation: Fluorescent aerolysin binds GPI anchors; absence on granulocytes or RBCs
detects clones down to 0.01%.
Question 3: Which complement regulatory protein is NOT GPI-linked?
A) CD55 (DAF)
B) CD59 (MIRL)
C) CD35 (CR1)
,D) CD46 (MCP)
Correct Answer: C) CD35 (CR1)
Explanation: CD46 and CD55/CD59 are GPI-anchored, whereas CD35 is a trans-membrane
protein and therefore preserved on PNH cells.
Question 4: Intravascular hemolysis in classic PNH is mediated chiefly by which pathway?
A) Classical complement
B) Lectin complement
C) Alternative complement
D) Extrinsic coagulation
Correct Answer: C) Alternative complement
Explanation: Uncontrolled "tick-over" C3b amplifies on GPI-deficient RBCs because
CD55/CD59 are missing, driving terminal-complement lysis.
Question 5: Which laboratory value best reflects the rate of ongoing hemolysis?
A) Serum ferritin
B) Lactate dehydrogenase (LDH)
C) Total protein
D) Albumin
Correct Answer: B) Lactate dehydrogenase (LDH)
Explanation: Massive release of LDH-1 from lysed RBCs provides a real-time, quantitative
index of complement-mediated destruction.
Question 6: Dark-colored morning urine in PNH is caused by:
A) Myoglobinuria
B) Porphyrinuria
C) Hemoglobinuria accumulated overnight
D) Bilirubinuria
,Correct Answer: C) Hemoglobinuria accumulated overnight
Explanation: Relative nocturnal hypoventilation causes mild respiratory acidosis that
activates complement; free hemoglobin is filtered and oxidizes in urine.
Question 7: Which cytokine predominates in the marrow failure phase of aplastic-PNH
syndrome?
A) IL-4
B) IFN-γ
C) IL-10
D) TGF-β
Correct Answer: B) IFN-γ
Explanation: Type-1 cytotoxic T cells secrete IFN-γ, suppressing normal GPI-positive stem
cells and selecting the PNH clone.
Question 8: The most frequent and life-threatening complication of classic PNH is:
A) Bleeding
B) Infection
C) Venous thrombosis
D) Amyloidosis
Correct Answer: C) Venous thrombosis
Explanation: Complement-activated platelets and NO depletion promote hyper-coagulability;
hepatic, cerebral, and dermal veins are classic sites.
Question 9: Which vascular territory is characteristically involved in Budd-Chiari due to PNH?
A) Superior mesenteric artery
B) Portal vein
C) Hepatic veins
D) Splenic artery
Correct Answer: C) Hepatic veins
, Explanation: Intra-abdominal venous thrombosis, especially hepatic veins, is
pathognomomonic for PNH-related thrombosis.
Question 10: Which finding distinguishes PNH hemolysis from autoimmune hemolytic
anemia?
A) Positive direct antiglobulin test
B) Splenomegaly
C) Elevated reticulocyte count
D) Negative direct antiglobulin test (DAT)
Correct Answer: D) Negative direct antiglobulin test (DAT)
Explanation: PNH is a complement-mediated, antibody-negative intravascular hemolysis; DAT
is negative unless allo-antibodies are present.
Question 11: Which GPI-linked antigen is used to gate PNH monocytes by flow?
A) CD14
B) CD16
C) CD64
D) CD11b
Correct Answer: A) CD14
Explanation: CD14 is strongly expressed and GPI-anchored; its absence together with FLAER
confirms monocytic PNH populations.
Question 12: Which of the following is a recommended pre-treatment before starting any
terminal-complement inhibitor?
A) Pneumococcal vaccine only
B) Meningococcal vaccines (ACWY + B) ≥2 weeks prior
C) Hepatitis A vaccine
D) Yellow-fever vaccine
Correct Answer: B) Meningococcal vaccines (ACWY + B) ≥2 weeks prior
QUESTIONS | 2025/2026
(Complete practice exam with verified answers &
rationales)
Question 1: Which somatic mutation underlies the GPI-anchor deficiency in PNH?
A) JAK2 V617F
B) PIGA
C) CALR exon 9
D) BCR-ABL
Correct Answer: B) PIGA
Explanation: A mutation in the X-linked PIGA gene disrupts the first step of
glycosylphosphatidylinositol (GPI) anchor synthesis, yielding the PNH clone.
Question 2: The earliest, most sensitive screening test for a PNH clone in 2025 is:
A) Ham (acidified-serum) test
B) Sucrose-lysis test
C) FLAER-based high-sensitivity flow cytometry
D) Serum haptoglobin
Correct Answer: C) FLAER-based high-sensitivity flow cytometry
Explanation: Fluorescent aerolysin binds GPI anchors; absence on granulocytes or RBCs
detects clones down to 0.01%.
Question 3: Which complement regulatory protein is NOT GPI-linked?
A) CD55 (DAF)
B) CD59 (MIRL)
C) CD35 (CR1)
,D) CD46 (MCP)
Correct Answer: C) CD35 (CR1)
Explanation: CD46 and CD55/CD59 are GPI-anchored, whereas CD35 is a trans-membrane
protein and therefore preserved on PNH cells.
Question 4: Intravascular hemolysis in classic PNH is mediated chiefly by which pathway?
A) Classical complement
B) Lectin complement
C) Alternative complement
D) Extrinsic coagulation
Correct Answer: C) Alternative complement
Explanation: Uncontrolled "tick-over" C3b amplifies on GPI-deficient RBCs because
CD55/CD59 are missing, driving terminal-complement lysis.
Question 5: Which laboratory value best reflects the rate of ongoing hemolysis?
A) Serum ferritin
B) Lactate dehydrogenase (LDH)
C) Total protein
D) Albumin
Correct Answer: B) Lactate dehydrogenase (LDH)
Explanation: Massive release of LDH-1 from lysed RBCs provides a real-time, quantitative
index of complement-mediated destruction.
Question 6: Dark-colored morning urine in PNH is caused by:
A) Myoglobinuria
B) Porphyrinuria
C) Hemoglobinuria accumulated overnight
D) Bilirubinuria
,Correct Answer: C) Hemoglobinuria accumulated overnight
Explanation: Relative nocturnal hypoventilation causes mild respiratory acidosis that
activates complement; free hemoglobin is filtered and oxidizes in urine.
Question 7: Which cytokine predominates in the marrow failure phase of aplastic-PNH
syndrome?
A) IL-4
B) IFN-γ
C) IL-10
D) TGF-β
Correct Answer: B) IFN-γ
Explanation: Type-1 cytotoxic T cells secrete IFN-γ, suppressing normal GPI-positive stem
cells and selecting the PNH clone.
Question 8: The most frequent and life-threatening complication of classic PNH is:
A) Bleeding
B) Infection
C) Venous thrombosis
D) Amyloidosis
Correct Answer: C) Venous thrombosis
Explanation: Complement-activated platelets and NO depletion promote hyper-coagulability;
hepatic, cerebral, and dermal veins are classic sites.
Question 9: Which vascular territory is characteristically involved in Budd-Chiari due to PNH?
A) Superior mesenteric artery
B) Portal vein
C) Hepatic veins
D) Splenic artery
Correct Answer: C) Hepatic veins
, Explanation: Intra-abdominal venous thrombosis, especially hepatic veins, is
pathognomomonic for PNH-related thrombosis.
Question 10: Which finding distinguishes PNH hemolysis from autoimmune hemolytic
anemia?
A) Positive direct antiglobulin test
B) Splenomegaly
C) Elevated reticulocyte count
D) Negative direct antiglobulin test (DAT)
Correct Answer: D) Negative direct antiglobulin test (DAT)
Explanation: PNH is a complement-mediated, antibody-negative intravascular hemolysis; DAT
is negative unless allo-antibodies are present.
Question 11: Which GPI-linked antigen is used to gate PNH monocytes by flow?
A) CD14
B) CD16
C) CD64
D) CD11b
Correct Answer: A) CD14
Explanation: CD14 is strongly expressed and GPI-anchored; its absence together with FLAER
confirms monocytic PNH populations.
Question 12: Which of the following is a recommended pre-treatment before starting any
terminal-complement inhibitor?
A) Pneumococcal vaccine only
B) Meningococcal vaccines (ACWY + B) ≥2 weeks prior
C) Hepatitis A vaccine
D) Yellow-fever vaccine
Correct Answer: B) Meningococcal vaccines (ACWY + B) ≥2 weeks prior
