Kinetics of heat-damaged homologous erythrocytes

Abstract

A new theoretical five-compartmental model (5CM) was developed for analysis of the clearance of heat-damaged erythroctes (HDE) labelled with chromium 51. Besides the HDE-spleen interaction, this new model also takes into account the interaction between extrasplenic reticuloendothelial (RES) sites and HDE, i.e. the hepatic clearance of fragmented erythrocytes (FE). Accordingly, HDE clearance curves are analysed into three exponential components, the fastest of which describes the RES-FE interaction, whereas the others describe the splenic clearance of spherocytes. Therefore, an estimation of the effective liver blood flow for HDE (ELBF) was achieved, along with a series of parameters describing splenic function. The 5CM proved to be more efficient than a previously proposed three-compartmental model (3CM) in the mathematical description of HDE clearance. Comparison was made by applying both models to 37 experimental curves obtained from 20 patients with congenital hemolytic anemias. The values for the splenic function parameters calculated by 5CM analysis and the strong correlations observed among them offer evidence that this model provides an adequate approximation to the real conditions under which HDE clearance takes place. Furthermore, a detailed quantitative analysis of the pooling of spherocytes within the spleen was attempted in this work, and this phenomenon was found to compete with splenic irreversible spherocyte trapping. The ELBF proved to be closely correlated with the hemodynamic splenic parameters, following first-order kinetics, as do low-dose colloids.

Temporal differences in membrane loss lead to distinct reticulocyte features in hereditary spherocytosis and in immune hemolytic anemia

“…Loss of cell surface area resulting in increased sphericity 18,23,24 is detrimental for red cell deformability and there is experimental evidence that these spherical cells are rapidly sequestered from circulation by the spleen. 5,9,11,[25][26][27][28][29][30] Hemolytic anemia characterized by spherocytic red cells with reduced membrane surface area is a feature of HS 1,2,19 and of some forms of AIHA. 4 In HS, the spherocyte formation has long been attributed to the increase propensity of abnormal red cells to shed membrane during their sojourn in circulation due to improper assembly of membrane proteins [6][7][8] whereas in AIHA it is due to partial phagocytosis 4 of the circulating red cell membrane bound antibodies complexes by macrophages.…”

“…The spherocytes are trapped in "red" pulp of the cords of Billroth 5,9,26,27 because they are less deformable 1,2,21,22 than normal red cells and thus not able to traverse through the endothelium of splenic sinuses. The trapped cells are subsequently destroyed by the macrophages.…”