sickling

Sickling is the reversible deformation of red blood cells from a normal disc shape to an elongated crescent form when hemoglobin S polymerizes in low-oxygen conditions. Sickle cell disease (SCD) results when a person inherits two abnormal HbS alleles (HbSS) or other HbS-containing genotypes; individuals with one HbS allele (HbAS) are usually asymptomatic but can sickle under stress.

Mechanism: Deoxygenated hemoglobin S polymerizes into long fibers that distort the cell, making it rigid and crescent-shaped. This reduces deformability, leading to hemolysis and vaso-occlusion. Triggers include hypoxia, acidosis, dehydration, fever, infections, high altitude, and strenuous exercise.

Clinical consequences: vaso-occlusive crises causing acute pain; acute chest syndrome; stroke; priapism; splenic sequestration; chronic hemolytic anemia; pigmented gallstones; and increased susceptibility to infections due to functional asplenia.

Diagnosis: newborn screening; confirmation with hemoglobin electrophoresis or high-performance liquid chromatography showing HbS; peripheral smear with sickled cells; genetic testing for HbS variants.

Management and prognosis: there is no universal cure; hematopoietic stem cell transplant may be curative in select cases. Disease-modifying therapies include hydroxyurea, L-glutamine, voxelotor, and crizanlizumab; supportive care includes analgesia, hydration, infection prevention, transfusion, vaccines, and avoidance of triggers. Life expectancy and quality of life have improved with comprehensive care.