Dense cells in sickle cell anemia: the effects of gene interaction

Abstract

In an attempt to uncover potential genetic sources of the clinical diversity of sickle cell anemia, we have characterized homozygous SS patients in the following ways: percentage of dense red blood cells (% F4) as determined from Percoll-Stractan continuous density gradients, alpha gene deletion, average percentage of hemoglobin F (% HbF), hemoglobin in g/dL, age, and sex. We find that alpha 4 individuals have a higher % F4 (mean 24% +/- 15%) than alpha 3 individuals (mean 12% +/- 8%) (P less than .005). Multivariate analysis demonstrated a significant correlation among % F4 levels and alpha-gene number and % HbF, and an interaction between the last two variables. The other variables considered did not significantly alter this model. As reported before, with fewer samples, we find that in the first ten years of life of SS individuals, the frequency of alpha gene deletion is 17%, which is comparable to that in the general black population, while in the group over 20 years of age, the frequency rises to 49%, implying that alpha thalassemia is associated with longer survival. These results indicate that it is necessary to consider sickle cell anemia not only as a single gene defect, but also as a disease whose clinical expression is the result of a group of genes capable of interacting at the phenotypic level.

Enhanced Gametocyte Formation in Young Erythrocytes by Plasmodium falciparum In Vitro

“…In exp. 58 a cell separation was also effected with a Percoll-Larex mixture (modified from a method used by Fabry et al [7]). This showed three layers of cells, not so well separated as in the Percoll alone.…”

The effect of Hb F and α‐thalassemia on the red cell indices in sickle cell anemia

“…The higher Hb and hemotocrit level in S/S patients with concomitant a-thalassemia, and to a slightly lesser extent in heterozygotes, is probably the result of reduced homolysis [30] and a more homogeneous red cell population, as demonstrated in density studies [25,32,33]. Although patients with a-thalassemia and high Hb F had slightly larger red cells and a higher Hb level, the differences between low and high Hb F groups with a-thalassemia were not significant.…”

Heat‐shock protein‐27, ‐70 and peroxiredoxin–II show molecular chaperone function in sickle red cells: Evidence from transgenic sickle cell mouse model

“…However, most of the acute clinical manifestations of SCD are related to acute VOCs, which represents the first cause of hospitalization of a young-adult with SCD [1,6]. VOCs result from complex and still only partially known interactions between plasma factors and different cell types, including dense, dehydrated sickle cells and reticulocytes, endothelial cells, leukocytes and platelets [1, [10][11][12][13]. Pathophysiological studies have shown that the dense, dehydrated red cells play a central role in acute VOCs due to impaired flow as a consequence of either intravascular sickling or trapping of dense RBCs in post-capillary venules with associated microvascular obstruction and organ damage [1, 14,15].…”