Erythrocyte density in sickle cell syndromes is associated with specific clinical manifestations and hemolysis

Abstract

IntroductionAll homozygous patients with sickle-cell disease (SCD) carry the same genetic defect in the ␤-globin genes. However, the clinical presentation and overall severity of their disease vary greatly, from milder forms that can go undetected for decades to extremely severe forms with multiorgan damage and early mortality. Identification of risk factor(s) and laboratory parameters that might be predictive of SCD severity or complications has important implications not only for understanding the pathophysiology of the disease but also for clinical management.A distinguishing characteristic of SCD is erythrocyte dehydration, because of K ϩ efflux from the red blood cell (RBC) and consequently decreased intracellular water content and increased mean corpuscular hemoglobin concentration. 1,2 Eaton and Hofrichter reported that the rate of the initial polymerization phase depends on the 20th-40th power of hemoglobin S (HbS) concentration. 3 HbS polymerization and sickling rates can be substantially reduced with relatively small diminutions of the intracellular HbS concentration. [3][4][5] Notably, in dense RBCs (DRBCs), defined as having a density exceeding 1.120, the intracellular total Hb concentration is increased from the normal (ϳ 33 g/dL) to 40-50 g/ dL. 6 DRBCs exhibit increased rigidity and decreased stability and include a variable fraction of irreversibly sickled cells. 7,8 The DRBC fraction varies within most patients with SCD with wide interpatient variations. 6,9 However, in earlier reports, no correlations could be established between DRBCs and clinical SCD severity. Most of those published studies were underpowered to detect this kind of interaction, which requires large numbers of well-characterized patients, and yielded contradictory findings. 10,11 Moreover DRBCs have never been studied for their potential association with chronic organ damage, which is increasingly being observed today because of the recent improvements in life expectancy.Similarly, the lack of precise clinical correlates for the percentage of DRBCs (% DRBCs) has not allowed assessing the potential additional indications for hydroxycarbamide (HC; hydroxyurea), which is currently indicated for the prevention of vaso-occlusive crises (VOCs) or acute chest syndrome (ACS).Herein, we compared data on RBC density with clinical and hematologic, biochemical, and genetic parameters in a large cohort of homozygous adult patients with SCD with the goal of identifying association with phenotypes and parameters indicative of severity. This population is unique for representing African immigrants with little white admixture and little admixture of haplotypes, contrary to what is seen in American patients.We also studied the effect of hydroxycarbamide on the % DRBCs. Methods PatientsAll patients with SS SCD regularly followed in our Center for Sickle Cell Disease at the Hopital Henri Mondor (Creteil, France), for whom a RBC For personal use only. on May 9, 2018. by guest www.bloodjournal.org From density measurement was available before hydro...

The paradox of the serrated sickle erythrocyte: The importance of the red blood cell membrane topography

“…A subsequent study showed patients whose RBC deformability averaged 37% or less of control values and whose dense cells averaged 22% of total circulating cells had fewer VOCs, less mortality, higher incidence of leg ulcers, and lower incidence of urinary tract infection although their Hb F was relatively low [8]. These findings are supported by another recent study [9]. In addition, it has been reported that sickle cell anemia with the highest reduction of RBC deformability were at lower risk to have osteonecrosis [10], another complication for the vaso-occlusive phenotype [11].…”

Density-based separation in multiphase systems provides a simple method to identify sickle cell disease

“…Factors that can affect the amount of dense cells present in the blood include hydration and the occurrence of a recent vaso-occlusive crisis (30). Under most conditions, however, the blood of individuals with SCD has 13% (SD 8%) dense cells (29). This estimate of the amount of dense cells present includes a large population and modulators that can reduce the amount of dense cells present, such as high levels of Hb F and concurrent α-thalassemia.…”

“…renal dysfunction) (29). Monitoring the distribution of the density of cells could also provide a way to assess sickle crises (30).…”

Critical Reviews: How we treat sickle cell patients with leg ulcers

“…Genomics analyses have shown an association in both conditions with genetic polymorphisms in the BMP6, TGFBR3 and Klotho genes, important in vascular biology, including regulation of NO production [29,36]. There has been evidence of severely impaired red cell deformability, increased density and altered rheology [22,33,37]. SCD leg ulcers have been linked to venous incompetence and vasomotor alterations [13,38,39].…”