Effects of Fibrinogen and α2‐Macroglobulin and Their Apheretic Elimination on General Blood Rheology and Rheological Characteristics of Red Blood Cell Aggregates

Abstract

Methods of therapeutic apheresis, such as plasma exchange or rheopheresis eliminate moderately aggregating macromolecules like fibrinogen, as well as strongly aggregating substances like alpha2-macroglobulin from blood. In order to examine the specific effect of eliminating alpha2-macroglobulin as a highly aggregating macromolecule, this study aimed to analyze the different rheological properties of: (i) moderately aggregating red blood cells (RBCs; inducible by fibrinogen); and (ii) strongly aggregating RBCs (inducible by alpha2-macroglobulin). In vitro, RBC aggregate geometry was determined in the presence of strong and moderate aggregation inducing macromolecules. In vivo, flow behavior of RBC aggregates was analyzed by intravital microscopy. Using network scanning, the number of perfused and non-perfused microvessels was determined. In vitro, the higher adhesive forces of strongly aggregating RBCs led to both a higher packing density of single RBCs within aggregates, expressed as a significantly reduced thickness of individual RBCs, and greater deformation, expressed as a significantly diminished offset between RBCs and an increased curvature of RBCs at the ends of the aggregates. In vivo rheoscopy showed that only high aggregating RBCs persisted in the precapillary bed and led to the absence of RBCs in up to 40% of nutritive capillaries. These novel findings are of importance regarding recent developments in clinical hemorheology, specifically the clinical use of hemapheretic therapies for diseases in which impaired microcirculation plays a role in either their development or progression, such as age-related macular degeneration and complications of diabetes mellitus. Our data support that procedures reducing the concentration of alpha2-macroglobulin in blood by extracorporeal elimination might provide a more efficient improvement of overall blood fluidity in microcirculatory beds.