Physicochemical basis and clinical implications of red cell aggregation

Abstract

In aggregation of red blood cells (RBCs) induced by macromolecules, the aggregating energy provided by macromolecular binding to RBC membrane must overcome the disaggregation energy of electrostatic repulsion between RBC surfaces and the effects of mechanical shear stress. Computation of net aggregation energy per unit area (γ_a) from changes in membrane strain energy in stationary RBC aggregates in dextrans and lectins yielded values of 10⁻² to 10⁻³ ergs/cm². The difference in γ_a between normal and neuraminidase-treated RBCs represents the electrostatic repulsive energy. Moderate shearing enhances RBC aggregation by promoting cell-cell encounter, but high shear stresses cause RBC disaggregation. The energy required to disaggregate a unit interacting area of RBCs in a flow channel (γ_d) is on the order of 10⁻⁴ ergs/cm2. The difference between γ_d and γ_a suggests that the macromolecular bonds may not have to be broken during shear disaggregation. RBC aggregation can cause an elevation of bulk viscosity of the blood (η_B), but the phase separation due to strong RBC aggregation may have an opposite effect on TlB. The rheological effect of RBC aggregation can also be affected by the geometry of the vessels through which blood flows. Therefore, RBC aggregation exerts complex effects on blood flow resistance and hemodynamics in vivo. RBC aggregation is more prone to occur in the low shear regions of postcapillary venules; the resulting preferential increase of post capillary resistance over precapillary resistance may lead to an elevation of capillary pressure and transcapillary fluid loss. When blood viscosity is elevated by enhanced RBC aggregation, the optimum hematocrit for oxygen transport is shifted to lower levels; hence the low hematocrit values found in paraproteinemias and hemorrhage serve to maintain oxygen transport to tissues.