Leg Ulcers in Sickle Cell Disease: A Multifactorial Analysis Highlights the Hemolytic Profile

Sickle cell disease (SCD) is characterized by the presence of the variant S hemoglobin (HbS). The homozygous genotype (HbSS) is sickle cell anemia (SCA), while the double heterozygous of HbS and HbC (HbSC) is defined as SC hemoglobinopathy. The pathophysiology is based on chronic hemolysis, inflammation, endothelial dysfunction, and vaso-occlusion, which results in vasculopathy and serious clinical manifestations. Sickle leg ulcers (SLUs) are cutaneous lesions around the malleoli frequent in 20% of Brazilian patients with SCD. SLUs present a variable clinical and laboratory pattern modulated by several characteristics that are not fully understood. Hence, this study aimed to investigate laboratory biomarkers and genetic and clinical parameters associated with the development of SLUs. This descriptive cross-sectional study included 69 SCD patients, 52 without SLU (SLU-) and 17 with active or previous SLU history (SLU+). The results showed a higher incidence of SLU in SCA patients and there was no observed association of alpha-3.7 Kb thalassemia in SLU occurrence. Alterations in NO metabolism and hemolysis were associated with clinical evolution and severity of SLU, in addition to hemolysis modulating the etiology and recurrence of SLU. Our multifactorial analyses demonstrate and extend the role of hemolysis driving the pathophysiological mechanism of SLU.

Automated summary

Sickle cell disease (SCD) is a condition characterized by the presence of variant S hemoglobin (HbS). Sickle cell anemia (SCA) occurs in individuals with a homozygous genotype (HbSS), while SC hemoglobinopathy refers to individuals with a double heterozygous genotype of HbS and HbC (HbSC). The pathophysiology involves chronic hemolysis, inflammation, endothelial dysfunction, and vaso-occlusion, leading to vascular disease and severe clinical manifestations.