Vaso-occlusive phenomena and hemolysis are the clinical hallmarks of sickle cell disease (SCD), an inherited disorder due to homozygosity for the abnormal hemoglobin, hemoglobin S (HbS). Vasoocclusion results in recurrent painful episodes (previously called sickle cell crisis) and a variety of serious organ system complications that can lead to life-long disabilities and/or early death.
Hemoglobin S (HbS), results from the substitution of a valine for glutamic acid as the sixth amino acid of the beta globin chain, which produces a hemoglobin tetramer (alpha2/beta S2) that is poorly soluble when deoxygenated . The polymerization of deoxy HbS is essential to vaso-occlusive phenomena . The polymer assumes the form of an elongated rope-like fiber, which usually aligns with other fibers, resulting in distortion into the classic crescent or sickle shape (image 1) and a marked decrease in red cell deformability. (See "Sickle hemoglobin polymer: Structure and functional properties".)
This polymerization process is altered by several factors. Fetal hemoglobin (HbF) is a major modulator of polymerization in that the higher the HbF levels, the more benign the clinical and hematologic features of sickle cell anemia . However, polymerization alone does not account for the pathophysiology of SCD. Subsequent changes in red cell membrane structure and function, disordered cell volume control, and increased adherence to vascular endothelium also play an important role [1,3].
An overview of the clinical manifestations of homozygous SCD will be presented here, with more complete discussions of the major clinical manifestations presented separately (eg, pulmonary, renal, bone and joint, cerebrovascular disease) . The diagnosis and treatment of SCD and the management of pregnancy in SCD are also discussed separately. (See "Diagnosis of sickle cell disorders" and "Overview of the management and prognosis of sickle cell disease" and "Hydroxyurea and other disease-modifying therapies in sickle cell disease" and "Pregnancy in women with sickle cell disease".)
The clinical manifestations of sickle cell disease vary markedly among the major genotypes. The following general principles apply to the major sickle cell subtypes. However, within each subtype, there can be a marked variability in disease severity. (See "Variant sickle cell syndromes".)