A 25-year-old Nigerian man with sickle cell disease (HbSS) develops acute chest syndrome. The pathogenesis of in situ pulmonary microvascular occlusion in this context involves which key adhesion event?

• A Complement-mediated opsonization of sickled cells by C3b
• B IgG autoantibody-mediated direct agglutination of sickled erythrocytes
• C Loss of glycophorin C leading to mechanical rigidity alone
• D HbS polymer-mediated erythrocyte binding to VCAM-1 via erythrocyte VLA-4 and to E-selectin ✓

Explanation

Acute chest syndrome pathogenesis involves multi-step vaso-occlusion: deoxygenated HbS polymerizes, rigidifying erythrocytes; these cells overexpress VLA-4 (α4β1 integrin) which binds VCAM-1 and fibronectin on endothelium, and the activated endothelium (triggered by inflammatory cytokines and hypoxia) upregulates E-selectin and P-selectin further trapping sickled cells. Complement opsonization and autoantibody agglutination characterize warm-type AIHA, not sickle cell pathophysiology.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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