In sickle cell disease, the vasoocclusion in small vessels during crisis is initiated primarily by which molecular mechanism?
- A HbS polymerization at low O2 tension, causing RBC sickling and increased viscosity ✓
- B Hemolysis-driven release of free hemoglobin scavenging nitric oxide, causing vasoconstriction
- C Complement activation on sickled cells causing platelet aggregation
- D Abnormal neutrophil-endothelial adhesion via E-selectin independent of HbS polymerization
Correct answer: A. HbS polymerization at low O2 tension, causing RBC sickling and increased viscosity
Explanation
The primary initiating event in sickle cell vasoocclusion is deoxygenation-induced polymerization of HbS (β6 Glu→Val substitution creates a hydrophobic sticky patch). Repeated sickling damages the RBC membrane, causing increased adhesiveness to endothelium via VCAM-1 and αvβ3 integrin. However, hemolysis-driven NO scavenging (option B) contributes significantly to vasculopathy and is a distinct mechanism explaining pulmonary hypertension and stroke. The primary initiating event in acute vasoocclusion is HbS polymerization causing erythrocyte rigidity.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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