Pathophysiologic significance of mechanical fragility of red blood cells

Abstract

To elucidate the pathophysiologic significance of the mechanical fragility of red blood cells (RBC), we have developed a simple quantitative technique, the impact-force method, for measuring mechanical hemolysis; the method makes use of the instantaneous falling of a metal bar due to gravity. The mechanical hemolysis thus induced was accompanied by cell fragmentation and echinocytosis. The method can be performed under near physiologic conditions. We found that mechanical hemolysis increased with a rise in hematocrit (Hct) value; in particular, the hemolysis rapidly increased above a Hct value of around 50%, thereby suggesting that the mechanical fragility determined by this method reflects the rheologic characteristics of the RBC suspension, such as cell-cell interactions, as well as membrane stability. Using the impact-force method, we found that the mechanical fragility of rat RBC was greater than that of human RBC, whereas there was little difference between the two species in osmotic fragility. Although osmotic hemolysis was strongly reduced by low concentrations of chlorpromazine, this drug promoted mechanical hemolysis at all concentrations examined. More interestingly, Heinz body-forming RBC from a patient with unstable hemoglobin disease and hemolytic anemia showed a marked increase in mechanical fragility, but a pronounced decrease in osmotic fragility due to dehydration of the cells. This suggests the pathophysiologic importance of the mechanical fragility of RBC, specifically in the pathogenesis of hemolytic disease. It is, therefore, likely that this mechanical fragility test could be of value in various related fields of clinical medicine, as well as hematology.