Microcyte

Abstract: Heterozygous alpha and beta thalassemia are extremely frequent in malaria endemic areas displaying a well balanced hematological situation with very mild anemia and microcytic red cells. There is widespread consensus that thalassemia determines resistance to severe malaria although the molecular basis of the mechanism of resistance is not understood. A few studies indicate that the thalassemic cell environment does not directly harm the parasites but apparently induces the loss of viability of infected red cells and their enhanced removal by macrophages. The difficulty to develop an hypothesis on the mechanism of malaria resistance largely derives from the substantial lack of knowledge on the physiology of thalassemic red cells in heterozygotes. Although causing only mild and asymptomatic anemia, the genetic defect causes unbalanced hemoglobin chain production. It is not understood how this large excess of globin chains can be removed without effecting the viability of the red cell. It is generally accepted that the loss of red cell membrane leading to microcytosis may represent the counterpart of hemoglobin chain excess removal but the mechanisms underlying this process are not defined. Our previous observations showed that in splenectomized intermediate thalassemia patients the Hb increase (from 7.7 to 9.1 g/dl) in comparison to non-splenectomized patients was due to a net increase of mean MCV (from 71 to 82 fl) and not to an increased number of red cells. This clinical evidence is not, therefore, in accordance with the concept that, in thalassemia, the spleen mainly acts to remove altered red cells but suggests that the spleen has an active role in reducing red cell volume. We have observed a larger amount of hemichromes bound to the red cell membrane in splenectomised patients. Those data are an indication that splenic macrophages exert a role in removing the hemichromes leading to a decrease of red cell volume. Histological studies show the role of splenic macrophages in “pitting” part of the red cell membrane containing hemichromes. Based on some recently published results and some preliminary data we developed the hypothesis that a physiological mechanism may permit the removal of abnormal globins deposited on the cytoplasmic side of the red cell membrane. This process should require a series of sequential events: a) binding of denatured globin chains to specific membrane protein ligands b) selective modification of the ligand bound to the globins to induce its clustering and the accumulation of all globin excess in a limited area of the membrane c) some mechanism leading to the recognition and binding of the clustered globin ligand by macrophages d) weakening of membrane structure in the area of denatured globin accumulation to allow its selective removal by macrophages and/or vesiculation of locally destabilized areas without interfering with the overall integrity of red cell membrane. This mechanism should allow globin excess removal minimizing the area of the membrane to be sacrificed therefore obtaining smaller but still viable biconcave red cells.

Abstract: A 17 year old non-vegetarian Asian female student presented with a three year history of increasing lethargy and shortness of breath during exercise. On examination she was clinically anaemic but had no other physical signs. Haematological investigations, including a blood film (fig 1⇓), were performed. Her haemoglobin was 85 g/l (normal range 120-160 g/l), mean cell volume was 79 fl (80-96 fl), mean cell haemoglobin was 25 pg (27.3-32.6 pg), haematocrit was 29% (0.36%-0.44%), white blood cell count was 5.0×109/l (4-11×109/l), differential cell count was normal, and platelets were 550×109/l (150-400×109/l). Fig 1 The patient’s blood film ### Short answers Fig 2 The patient’s blood film showing microcytosis (red arrow), hypochromia (green arrow), and pencil cells (black arrow) ### Long answers #### 1. Abnormalities The blood film (fig 2⇑) showed microcytosis, hypochromia, and pencil cells. Microcytes (red arrow) have normal morphology but are smaller than normal red blood cells. By definition the volume of a microcyte does not exceed 80 fl (the lower limit of normal mean cell volume). When looking at a blood film, a normal sized red cell should be about the same …

Abstract: Hemoglobin (Hb) E and Hb Constant Spring (CS) are known to have thalassemia-like effects. Investigation on the red cell physical changes in these two abnormalities has been done to clarify the diversity of red cell changes between thalassemia and thalassemia-like abnormal hemoglobin (Hb E represents beta-thalassemia and Hb CS represents alpha-thalassemia). Eleven cases with homozygous Hb CS (CS/CS), 7 homozygous Hb E subjects (E/E) and one double heterozygous case with Hb CS and Hb E were included in this study. The red cells were analyzed by the H* 1 hematology analyzer. The E/E red cells had significantly smaller MCV than the CS/CS red cells (p < 0.001). The smaller MCV of E/E red cells was attributed to markedly increased percent microcyte (p < 0.001) and significantly lower percent macrocyte (p < 0.001) as compared to CS/CS red cells. Degree of heterogeneity in cell volume as indicated by red cell distribution width (RDW) was not significantly different between the two abnormal hemoglobin containing red cells. It was also noted that the CS/CS cases had a more significant increase in small RBC than the E/E cases (p < 0.001). Significant lower intraerythrocyte hemoglobin concentration values of the CS/CS red cells as compared to E/E red cells were shown: cellular hemoglobin concentration mean (CHCM) (p < 0.001), percent hyperchromic red cell (p < 0.001) and hemoglobin distribution width (HDW) (p = 0.0367). Higher values for the CS/CS red cells were MCH (p < 0.001) and percent hypochromic red cells (p < 0.001). Red cells from both genotypes had significant decreases in red cell deformability.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: The clinical blood analysis implemented at modern hematological analyzers can be used as a foundation for primary differentiated diagnostic of anemic syndrome related to true and functional iron deficiency in oncologic patients. The normocyte normochromic anemia with normal and higher level of hemoglobin of reticulocytes (RET-HE) testifies presence in higher degree of anemia of chronic diseases which is more often combined with higher content of serum ferritin (Ferr), lower level of soluble receptors of ferritin (sTfR) and production of erythropoietin (EPO) inadequate to anemia degree. The microcyte hypochromic anemia can be present both under iron-deficient anemia and under functional iron deficiency as a result of its blocking in macrophages under anemia of chronic diseases in oncologic patients. Hence the differentiated diagnostic of these states demands additional analysis of content of serum ferritin, soluble receptors of ferritin and production of erythropoietin.