Ultrastructural studies of the bone marrow in sickle cell anaemia. II. The morphology of erythropoietic cells and their response to deoxygenation in vitro.

Electron microscopic studies of bone marrow aspirates obtained from patients with homozygous sickle cell anaemia (HbSS) were fixed immediately without attempts to deoxygenate the samples. Erythroblasts and normoblasts in these preparations were devoid of haemoglobin polymers or other indications of sickling. Furthermore, the nucleated erythroid cells from sickle-cell patients presented an ultrastructural morphology indistinguishable from that of identically-processed erythroid cells in marrow samples from normal human volunteers. This report presents a description of the ultrastructural features of pronormoblasts and normoblasts in normal and sickle-cell marrows and stresses the essentially normal appearance of nucleated erythroid elements in sickle cell anaemia. Exposure of sickle-cell marrow aspirates to nitrogen at 37 degrees C for 30 min resulted in haemoglobin polymerization in most erythrocytes and reticulocytes but only in 10-20% of the nucleated erythroid cells. Haemoglobin polymers in the form of intertwining fibre meshworks were observed in reticulocytes, orthochromatic and polychromatophilic normoblasts, but were absent in basophilic normoblasts and pronormoblasts. The results suggest that the concentration of haemoglobin in intramedullary normoblasts may be the limiting factor determining the predisposition of these cells to undergo sickling as well as the pattern of haemoglobin aggregation. Under the physiological conditions prevailing in the marrow, haemoglobin concentration in normoblasts may be insufficient to result in aggregation and polymerization.