Defective erythropoietin production and reticulocyte response in acute Plasmodium falciparum malaria-associated anemia.

To elucidate the relationship between falciparum malaria-associated anemia and serum erythropoietin (Epo) levels and reticulocyte response during acute malaria infection, 87 adults aged 18-65 years presenting with acute, uncomplicated malaria were examined on enrollment and for 28 days of follow-up. The 87 patients were divided into 2 groups: those with anemia (n = 45) and those without (n = 42). Serum samples were taken on admission (Day 0), then on Days 7, 21, and 28, to measure the reticulocyte count, absolute reticulocyte count, reticulocyte hemoglobin content, and erythropoietin level (Epo). The absolute reticulocyte counts for the anemic patients were significantly higher than for those without anemia on Days 0, 7, 21, and 28. The serum Epo levels for the anemic patients were significantly higher than the non-anemic group only on Day 0 (44.39 +/- 4.06 vs 25.91 +/- 4.86 mlU/ml, p < 0.001). Inadequate Epo production was found in 31.03% (27/87) of patients on Day 0, 37.93% (33/87) on Day 7, 43.67% (38/87) on Day 21, and 39.08% (34/87) on Day 28. These results indicate defective Epo production and reticulocyte response in adult patients suffering from acute P. falciparum malaria, which differs from pediatric patients. Our findings may provide the basis for further study into the choice of therapeutic strategies to treat acute P. falciparum malaria-associated anemia with recombinant human Epo to correct refractory anemia due to malaria.

Different reticulocyte volume in diabetes mellitus patients with and without hypercholesterolemia and/or hypertriglyceridemia.

Red cells and reticulocytes from patients with diabetes mellitus (DM) were analysed using laser and computer technology of H*3 hematology analyzer. Four groups of diabetes mellitus patients: diabetes with normolipemia (DM) (n = 12) and DM patients with excess triglyceride (DM-T) (n = 7) or cholesterol (DM-C) (n = 21) or both (DM-TC) (n = 21) were studied. Mean corpuscular volume of mature red cells (Mean +/- SD = 93.6 +/- 5.5 fl) and reticulocyte (119.1 +/- 12.3 fl) of patients with DM-T was not significantly increased from normal (red cell, 90.0 +/- 3.5 fl; reticulocyte, 115.2 +/- 7.3 fl). Plasma triglyceride levels had no significant correlation with red cell MCV, reticulocyte MCV and %Hb A1c. This suggests that high triglyceride levels in DM are not dose-dependent in producing increased MCV of red cells and reticulocytes. Comparing between DM-T and DM-C, red cells and reticulocytes from DM-C patients had significantly decreased MCV (red cell, 85.5 +/- 6.1 fL; reticulocyte, 103.8 +/- 7.4 fL). Plasma cholesterol levels were inversely correlated with MCV of red cells (r = -0.377, p = 0.003) and also MCV of reticulocytes (r = -0.418, p = 0.001). In addition, cholesterol levels showed considerable correlation with Hb A1c (r = 0.572, p = 0.004). The red cell volume change in DM-C patients may be partly due to the shift in balance of cholesterol exchange between red cell membranes and serum lipoproteins.

Reticulocyte analysis in iron deficiency anemia and hemolytic anemia.

Reticulocyte analysis was studied in 28 anemic patients, 15 with iron deficiency anemia (IDA), and 13 with hemolytic anemia including 9 glucose 6 phosphate dehydrogenase deficiency (G6PD def.), and 4 with G6PD def. combined with HbE trait or alpha thalassemia trait (alpha thal trait). The reticulocyte analysis among these patients showed the increased number of reticulocyte percentage with low degree of maturation in both IDA and G6PD def. patients. The significantly decreased reticulocyte hemoglobin content (CHr) was found in IDA (CHr = 21.74 +/- 4.61 pg in IDA vs 28.41 +/- 1.34 pg in normal; p-value = < 0.0001), whereas, increased CHr was found in G6PD def. patients. In addition, the G6PD def. patients also showed a significant increase in mean corpuscular reticulocyte volume (MCVr) when compared to normal (MCVr = 132.0 +/- 8.39 fl. in G6PD def. vs 110.39 +/- 5.09 in normal; p-value = < 0.0001). However, a significant decrease in MCVr was found in IDA patients (MCVr = 95.89 +/- 8.57 fl.; p-value = < 0.0001 vs normal). From this study, we can suggest that the reticulocyte hemoglobin content (CHr) and mean corpuscular reticulocyte volume (MCVr) are the important defects in patients with iron deficiency anemia.

Ultrastructural aspects of the final stage of hemoglobin biosynthesis

Electron microscopic observations on rabbit embryo, adult rabbit, guinea pig, and human immature erythroid cells showed characteristic hemoglobinized organelles distinguishable from mitochondria by their highly dense matrix, two or three longitudinally arranged double lamellae, and smaller diameters. The presence of hemoglobin (Hb) within these organelles was also demonstrated by electrophoresis of the concentrated supernatant from the isolated, washed and osmotically lysec organelle fraction. The term hemosome has been suggested for these organelles because of their Hb content. We propose that they are the sites of heme integration into the four polypeptide globin chains. The frequency of hemosomes is higher in the peripheral blood erythorid cells of embryos than in the liver erythroid cells, coinciding with the higher Hb synthesis rate in peripheral blood than in the liver. Peripheral blood reticulocytes of rabbits with anemia induced by bleeding presented a lower hemosome frequency than normal reticulocytes. The decrease paralleled the decay of Hb biosynthesis activity. Moreover, Hb biosynthesis induced in HeLa cell and epithelial cell tissue cultures was always associated with the formation of hemosomes. Hemosomegenesis was studied in epithelial tissue culture cells experimentally induced to synthesize Hb, allowing the identification of several stages of hemosome formation in erythroid cells. The morphological data suggest that mitochondria are successively modified to lamellated...