A transfusion medicine specialist uses the zeta potential concept to understand RBC aggregation. Which property of normal RBCs prevents spontaneous agglutination in vivo?

• A Positive surface charge from glycocalyx sialic acid residues creating electrostatic repulsion between RBCs
• B Negative surface charge (zeta potential) from sialic acid-rich glycophorin creating repulsive force preventing rouleaux formation ✓
• C Biconcave disc shape reducing surface area for cell-cell contact and rouleaux tendency
• D Normal plasma protein composition with low fibrinogen preventing bridging agglutination

Explanation

The outer surface of RBCs is covered with sialic acid residues on glycophorin A and C and other glycoproteins, giving RBCs a net negative surface charge (negative zeta potential of approximately -15 mV). This creates electrostatic repulsion between red cells, preventing them from approaching close enough to aggregate. In inflammatory states, fibrinogen and globulins (bridging proteins) can overcome this repulsion, causing rouleaux formation and elevated ESR. Option A has the charge sign reversed (sialic acid gives negative charge). Option C is a physical advantage for deformability but not the primary anti-aggregation force. Option D is the plasma-side factor.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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