Red cell filtration and the pathogenesis of certain hemolytic anemias.

By JAMES H. JANDL, RICHARD L. SI f sfoNS AND WILLIAM B. CAsTLE T HERE APPEAR to be two mechanisms whereby red cells are destroyed in vivo. First, they may undergo disruption or dissolution within the general circulation, as by the action of immune, bacterial, or chemical lysins, causing the clinical picture of “intravascular hernolvsis.” Second, and more commonly, red cells may be trapped or sequestered in certain regions of the circulation, particularly in the spleen and liver,1 in which case the cellular hemoglobin is largely degraded in situ and the clinical picture is of “extravascular hemolysis.” There are two proposed primary mechanisms whereby red cells may be so sequestered: by a surface adherence of the cells to the endothelial or reticuloendothelial cells lining the blood vessels, essentially a chemical or electrostatic process; or by simple filtration, essentially a physical process.2 Conceivably, of course, both processes may operate in unison, as by chemical or electrostatic interactions between the surfaces of reticuloendothelial cells and of physically trapped red cells. The phenomenon of phagocytosis, often written of in the literature on the reticuloendothelial system as synonymous with sequestration, is inescapably a process secondary to those described above. Sequential pathologic studies of the reticuloendothelial tissues have been made in rats during the destruction of red cells altered in various ways not in themselves lytic in vitro:3 erythrophagocytosis of cells so altered was a delayed, usually post-hemolytic process in vivo. In an effort to understand the behavior of normal and altered red cells in the capillary “filter-beds” of the body, studies were undertaken of their behavior in respect to artificial filters in vitro. After cr’ide, preliminary studies with ordinary paper fiber filters, more exact experiments were carried out employing Millipore#{176} membrane filters. Unlike fibrous filters, the membrane filter consists of a chemically inert matrix penetrated by non-branching capillary tubes oriented perpendicularly to the filter surface, providing a structural