Sickle cell disease (SCD) occurs due to a mutation of normal adult hemoglobin (HbA). HbA consists of two alpha (α) globins and two beta (β) globins. Each globin contains a heme molecule with an iron atom that binds oxygen and carbon dioxide. Normal adult red blood cells (RBCs) contain mostly HbA. (Note that fetal hemoglobin, or HbF, is a second type of normal hemoglobin that predominates during most of gestation).
SCD results from a mutation in the beta globin of hemoglobin. This mutation produces the abnormal hemoglobin, HbS.
Complications from HbS
In low-oxygen conditions, HbS can form polymers, or strands, that cause RBCs to assume the sickle shape characteristic of this complex disease.
When RBCs sickle, they become fragile and can easily rupture. Compared with the 100- to 120-day life span of a normal RBC, sickle RBCs have an average life span of only about 20 days. This causes a chronic hemolytic anemia that adversely affects the lives of people with sickle cell disease.
Sickle RBCs adhere to vascular endothelial cells more than normal. They also interact with other cells, including white blood cells and platelets. These interactions are mediated by adhesion molecules, including selectins. This obstructs the flow of blood within the vessels, producing vaso-occlusion and reperfusion injury when blood supply returns to the affected tissue. Vaso-occlusive crisis can occur.
Hemolysis of sickle RBCs releases intracellular components into the bloodstream, causing coagulation and inflammation. Free heme decreases nitric oxide, causing oxidative stress, inflammation, and endothelial dysfunction. Chronic leukocytosis — abnormal activation of neutrophils and monocytes — also increases inflammation, resulting in a vasculopathy that can lead to organ damage.
Because of its unique characteristics, the blood of patients with SCD separates differently from the blood of other patients, complicating cell collection for cell and gene therapy procedures. To see how data helped optimize procedure outcomes at Boston Children’s Hospital,
read this case study.
Source
Terumo Blood and Cell Technologies. Red blood cell exchange procedures on Spectra Optia® Apheresis System.
Spectra Optia RBCX Sucessions Program. 2022;(v1.0).