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

Area of Science:

• Hematology
• Genetics
• Dermatology

Background:

• Sickle cell disease (SCD) involves variant hemoglobin S (HbS), leading to chronic hemolysis, inflammation, and vaso-occlusion.
• Sickle leg ulcers (SLUs) are common cutaneous manifestations in SCD patients, particularly in Brazil, with poorly understood contributing factors.
• Understanding SLU pathophysiology is crucial for managing this frequent complication of SCD.

Purpose of the Study:

• To investigate laboratory biomarkers, genetic factors, and clinical parameters associated with SLU development in SCD patients.
• To explore the role of hemolysis and nitric oxide (NO) metabolism in the pathophysiology and clinical presentation of SLUs.

Main Methods:

• A descriptive cross-sectional study involving 69 SCD patients, categorized into those with (SLU+) and without (SLU-) a history of leg ulcers.
• Analysis included assessment of genetic factors (e.g., α-3.7 Kb thalassemia), laboratory biomarkers related to NO metabolism and hemolysis, and clinical parameters.

Main Results:

• SLUs were more frequent in patients with sickle cell anemia (HbSS genotype).
• No association was found between α-3.7 Kb thalassemia and SLU occurrence.
• Alterations in nitric oxide metabolism and increased hemolysis correlated with the clinical evolution and severity of SLUs, with hemolysis also modulating etiology and recurrence.

Conclusions:

• Hemolysis is a significant driver of the pathophysiological mechanisms underlying SLU development and severity in SCD.
• NO metabolism alterations and hemolysis are key factors in the clinical progression of SLUs.
• These findings emphasize the multifactorial nature of SLUs and the central role of hemolysis.