PNH Haemolysis Mechanism Explained

Paroxysmal Nocturnal Haemoglobinuria (PNH) is characterized by haemolysis, specifically the destruction of red blood cells. The question asks for the primary underlying mechanism.

Understanding PNH Pathophysiology

• PNH results from a somatic mutation in the PIGA gene.
• This mutation impairs the synthesis of glycosylphosphatidylinositol (GPI) anchors.
• GPI anchors are essential for attaching certain proteins to the cell surface, including CD55 and CD59.
• CD55 and CD59 are crucial regulators that protect red blood cells from complement-mediated damage.
• In PNH, red blood cells lack sufficient amounts of these protective proteins, particularly CD59.

Primary Haemolysis Mechanism in PNH

The deficiency of CD59 makes the red blood cells (RBCs) abnormally sensitive to lysis by the complement system. The uncontrolled activation of the complement cascade leads to the formation of the membrane attack complex (MAC) on the RBC surface, causing intravascular haemolysis.

Therefore, the primary underlying mechanism is complement-mediated destruction of CD59(-) red blood cells.

Evaluating Other Options

• ABO incompatibility: This relates to immune reactions during blood transfusions, not the intrinsic defect in PNH.
• Red cell fragmentation: While some fragmentation can occur secondary to lysis, it is not the primary initiating mechanism in PNH.
• Exotoxins produced by Clostridium perfringens: These toxins cause haemolysis in specific infections (like gas gangrene), unrelated to the mechanism in PNH.

Based on the pathophysiology, option C accurately describes the core issue leading to haemolysis in PNH.