Leg ulcers in sickle cell disease: a multifactorial analysis highlights the hemolytic profile

Abstract: 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 (SLU) are cutaneous lesions around the malleoli frequent in 20% of Brazilian patients with SCD. SLU present a variable clinical and laboratory pattern modulated by several characteristics that are not fully understood. Hence, this study aimed to investigate biomarkers laboratory, genetic and clinical parameters associated with development of SLU. 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 high incidence of SLU in SCA patients and there was no observed relation of α-3.7Kb thalassemia in SLU occurrence. Alterations in NO metabolism and hemolysis were associated with clinical evolution and severity of SLU, in addition to hemolysis modulate the etiology and recurrence of SLU. Our multifactorial analyses demonstrate and extent the role of hemolysis driving the pathophysiological mechanism of SLU