Sickle cell disease (SCD) consists of a group of hemoglobinopathies in which individuals present highly variable clinical manifestations. Sickle cell anemia (SCA) is the most severe form, while SC hemoglobinopathy (HbSC) is thought to be milder. Thus, we investigated the clinical manifestations and laboratory parameters by comparing each SCD genotype. We designed a cross-sectional study including 126 SCA individuals and 55 HbSC individuals in steady-state. Hematological, biochemical and inflammatory characterization was performed as well as investigation of previous history of clinical events. SCA patients exhibited most prominent anemia, hemolysis, leukocytosis and inflammation, whereas HbSC patients had increased lipid determinations. The main cause of hospitalization was pain crises on both genotypes. Vaso-occlusive events and pain crises were associated with hematological, inflammatory and anemia biomarkers on both groups. Cluster analysis reveals hematological, inflammatory, hemolytic, endothelial dysfunction and anemia biomarkers in HbSC disease as well as SCA. The results found herein corroborate with previous studies suggesting that SCA and HbSC, although may be similar from the genetic point of view, exhibit different clinical manifestations and laboratory alterations which are useful to monitor the clinical course of each genotype.

Introduction. Clinical complications in sickle cell anemia (SCA) are heterogeneous and involve several molecules. It has been suggested that SCA individuals present a dyslipidemic phenotype and that lipid parameters are associated with severe clinical complications, such as pulmonary hypertension. We sought to investigate associations between lipid parameters and clinical manifestations, as well as other laboratory parameters in a population of pediatric SCA patients. Methods. Our cross-sectional evaluation included 126 SCA patients in steady state and who were not undergoing lipid-lowering therapy. Hematological and biochemical parameters were characterized, and previous clinical manifestations were investigated. Results. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were increased in patients with a previous history of pneumonia, which also positively correlated with HbS levels. Decreased LDL-C levels were also associated with leg ulcers and anemia. Elevated high-density lipoprotein cholesterol (HDL-C) levels were associated with pain crises, increased viscosity, and decreased hemolysis. Several studies have determined that lipids play a role in the vascular impairment seen in SCA, which was corroborated by our findings. Conclusions. In sum, our results suggest that total cholesterol, HDL-C, and LDL-C levels are associated with hemolysis and anemia markers and, most importantly, with clinical complications related to vasculopathy in SCA.

Priapism is a urologic emergency characterized by an uncontrolled, persistent and painful erection in the absence of sexual stimulation, which can lead to penile fibrosis and impotence. It is highly frequent in sickle cell disease (SCD) associated with hemolytic episodes. Our aim was to investigate molecules that may participate in the regulation of vascular tone. Eighty eight individuals with SCD were included, of whom thirty-seven reported a history of priapism. Priapism was found to be associated with alterations in laboratory biomarkers, as well as lower levels of HbF. Patients with sickle cell anemia using hydroxyurea and those who received blood products seemed to be less affected by priapism. Multivariate analysis suggested that low HbF and NOm were independently associated with priapism. The frequency of polymorphisms in genes NOS3 and EDN1 was not statistically significant between the studied groups, and the presence of the variant allele was not associated with alterations in NOm and ET-1 levels in patients with SCD. The presence of the variant allele in the polymorphisms investigated did not reveal any influence on the occurrence priapism. Future studies involving larger samples, as well as investigations including patients in priapism crisis, could contribute to an enhanced understanding of the development of priapism in SCD.

Differences in hydroxyurea response in sickle cell anemia may arise due to a series of factors with genetic factors appearing to be predominant. This study aims to investigate the effects of single nucleotide polymorphisms in genes encoding drug-metabolizing enzymes and solute carriers on hydroxyurea response, in patients with sickle cell anemia. For that purpose, a total number of 90 patients with sickle cell anemia were recruited, 45 were undergoing hydroxyurea treatment, while 45 were not under the treatment. Association analyses were performed between CYP3A4 (rs2740574), CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and laboratory parameters. According to our findings, patients with hydroxyurea treatment demonstrated higher HbF levels and a significant improvement in hemolytic, hepatic, inflammatory, and lipid parameters in comparison to those without the treatment. We also found significant associations between the CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and an improvement of the therapeutic effects, specifically the hemolytic, hepatic, inflammatory, lipid, and renal parameters. In conclusion, our results highlight the importance of the investigated variants, and their strong association with hydroxyurea efficacy in patients with sickle cell anemia, which may be considered in the future as genetic markers.