**Question:** PNH due to defect in -

A. **Erythrocyte** membrane damage
B. **Platelet** function
C. **Neutrophil** function
D. **Lysosomal** enzyme activity

**Correct Answer:** **C. Neutrophil function**

**Core Concept:** Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired blood disorder characterized by hemolysis, thrombosis, and bone marrow failure due to a deficiency in the membrane proteins, particularly the glycosylphosphatidylinositol (GPI) anchored proteins.

**Why the Correct Answer is Right:** PNH results from a defect in the **neutrophil** function, specifically in the **glycosylphosphatidylinositol (GPI) anchored proteins**. These proteins are crucial for the stability and integrity of the **erythrocyte** membrane, preventing hemolysis. In PNH, a deficiency of these proteins leads to increased susceptibility of erythrocytes to lysis by **autoantibodies** and **complement activation**. Additionally, the deficiency affects the **neutrophil** function, causing impaired phagocytosis and bactericidal activity, increasing the risk of infections.

**Why Each Wrong Option is Incorrect:**

A. Erythrocyte membrane damage (Option A) is not the correct answer because PNH primarily affects **neutrophils** and **erythrocytes**, not specifically erythrocyte membrane damage.

B. Platelet function (Option B) is incorrect because PNH primarily affects **neutrophils** and **erythrocytes**, not platelets. The deficiency in GPI-anchored proteins does not directly affect platelet function.

C. Neutrophil function (Option C) is the correct answer, as described above. The deficiency in GPI-anchored proteins primarily affects **neutrophil** function, leading to hemolysis and thrombosis.

D. Lysosomal enzyme activity (Option D) is incorrect because the question focuses on GPI-anchored proteins, which are not directly related to lysosomal enzymes. The primary defect in PNH is the deficiency of GPI-anchored proteins, not lysosomal enzyme activity.

**Clinical Pearl:** PNH is a rare disorder with a prevalence of approximately 1 in 10,000 to 1 in 100,000 people. The diagnosis is confirmed by flow cytometry and clonal analysis of bone marrow or peripheral blood mononuclear cells. Treatment options include **eculizumab**, a monoclonal antibody that inhibits C5a complement activation, preventing hemolysis, and **transfusion therapy** for anemia. Prophylactic antibiotics are also recommended for the prevention of infections.