Affiliations: Department of Third Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo | Department of Physiology, Nippon Medical School, Bunkyo-ku, Tokyo | The Shiga Medical Center for Adult Diseases, Moriyama, Shiga, Japan | Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA
Note: [] Reprint requests to: Setsuo Hasegawa, M.D., Department of Third Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113, Japan
Abstract: To elucidate the pathogenesis of hemolysis in hereditary spherocytosis (HS), we studied the heterogeneity and deformability of red blood cells (RBCs), before and after splenectomy, in a typical patient with HS. RBC deform ability was measured with our recently developed nickel mesh filter with both 3μm and 5μm pores. HS RBCs showed a marked increase in osmotic fragility with a “tailed” osmotic-fragility curve; consistently, the density distribution of HS RBCs was markedly shifted to heavier cells, with a biphasic profile. HS RBCs, the dense cells in particular, showed a marked impairment in filterability through the 3-μm pore nickel mesh compared with that through the 5-μm pores. It is, therefore, likely that the impaired deformability of HS RBCs arises from the decrease in the cell surface area to volume ratio and the high mean corpuscular hemoglobin concentration. After splenectomy, the dense microspherocytes disappeared, and there was a marked improvement in RBC filterability through 3-μm pores. This suggests that dense cells were microspherocytes that received splenic conditioning in the walls of splenic sinuses. Correspondingly, splenectomy markedly improved clinical manifestations and ameliorated hemolysis. Thus, the laboratory measurement (i.e., the 3-μm filtration test) reflected the patient's clinical state. The use of both 5- and 3-μm filtration measurements can make a practical contribution to determining the differential diagnosis of hereditary hemolytic anemias. The 3-μm filter is useful in determing the clinical severity and indications for splenectomy in HS.
