In sickle cell disease, the repeated sickling-unsickling cycle primarily leads to irreversible RBC membrane damage via which mechanism?

• A Complement activation forming MAC on RBC surface
• B Loss of spectrin-ankyrin cytoskeletal linkage causing membrane vesiculation ✓
• C Antibody-mediated Fc receptor engagement by macrophages
• D Direct osmotic lysis due to HbS polymerization

Explanation

Repeated cycles of sickling cause cumulative damage to the RBC cytoskeleton, particularly disrupting the spectrin-ankyrin-protein 4.1 network. This leads to loss of lipid bilayer phospholipid asymmetry, membrane vesiculation, and permanently deformed 'irreversibly sickled cells' that are rigid and have reduced survival. Complement-mediated lysis is PNH. Antibody-mediated is AIHA.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.