A 35-year-old man with sickle cell disease is admitted with acute chest syndrome. Which pathological mechanism is MOST responsible for the vaso-occlusion in sickle cell disease?

• A Extravascular hemolysis releasing heme that activates neutrophil extracellular traps
• B HbS-induced complement activation coating red cells and promoting platelet aggregation
• C HbS oxidation generating methemoglobin that causes endothelial nitric oxide quenching exclusively
• D HbS polymerization under deoxygenation causing rigid sickle-shaped red cells that obstruct microvascular flow ✓

Explanation

In sickle cell disease, deoxygenation promotes hydrophobic interactions between HbS molecules causing polymerization into long fibers that distort erythrocytes into the classic sickle shape. These rigid, deformed cells adhere to endothelium and occlude the microcirculation, producing vaso-occlusive crises and acute chest syndrome. While nitric oxide depletion and inflammation contribute to vascular dysfunction, the primary pathological event triggering vaso-occlusion is HbS polymerization.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.