SCA is a genetic blood disorder caused by a mutation in the hemoglobin gene, the protein responsible for oxygen transport in red blood cells. This mutation causes normally round, flexible red blood cells to become stiff and crescent- or “sickle”-shaped. These sickle cells can block blood flow in small vessels. Because early detection and intervention significantly improve health outcomes, testing for SCA is necessary for managing the condition.
Newborn Screening for Sickle Cell Disease
Newborn screening provides the earliest opportunity to detect sickle cell disease, making it a routine practice in the United States and many other countries. This process typically begins before the baby is discharged from the hospital, usually within the first one to two days of life. A small blood sample is collected from the infant’s heel in a procedure often called a “heel prick” or “heel stick.”
The few drops of blood are placed onto a specialized filter paper card and sent to a public health laboratory for analysis. This initial testing is a screening, not a definitive diagnosis, designed for rapid detection of abnormal hemoglobin types. If the screening result is positive, a second, more conclusive test is required to confirm the diagnosis and determine the exact type of sickle cell condition.
The primary purpose of this quick screening is to identify affected infants promptly so they can begin life-saving prophylactic treatments, such as penicillin, to prevent serious bacterial infections. Early diagnosis allows families and healthcare providers to establish specialized care immediately, which is crucial for managing the disease and reducing the risk of complications.
Definitive Diagnostic Testing Methods
When a newborn screening result is positive or when an older child or adult shows symptoms, definitive laboratory methods are used to confirm the presence and type of abnormal hemoglobin. The gold-standard tests involve separating and measuring the various kinds of hemoglobin present in a blood sample. These techniques allow for a precise profile of the hemoglobin variants.
One of the most common methods is Hemoglobin Electrophoresis, which separates hemoglobin components based on their electrical charge as they move through a gel medium. This process clearly identifies the presence of Hemoglobin S (HbS), the abnormal form that causes sickling, distinguishing it from normal adult hemoglobin (HbA) and other variants. High-Performance Liquid Chromatography (HPLC) is another highly sensitive method that quantifies the exact percentage of each hemoglobin type.
HPLC separates the hemoglobins based on their chemical properties, providing a detailed breakdown of the blood’s composition, including the amounts of HbA, HbS, and fetal hemoglobin (HbF). For cases where the initial biochemical results are unclear or to determine the specific genetic mutation, DNA testing may be employed. This molecular analysis offers the most precise diagnosis by directly identifying the variation in the beta-globin gene responsible for the disease.
Prenatal and Carrier Screening
Testing can occur even before a person is born or before conception. Carrier screening is a simple blood test offered to prospective parents, especially those with a family history of sickle cell disease or those from high-risk ethnic backgrounds. This test determines if an individual carries the sickle cell trait, meaning they have one normal hemoglobin gene and one abnormal gene (HbAS).
If both parents are identified as carriers, they have a one-in-four chance with each pregnancy of having a child with the full disease. In these high-risk pregnancies, two procedures are available to determine the fetal status. Chorionic Villus Sampling (CVS) is performed between 10 and 13 weeks of gestation, using a small sample of placental tissue. Amniocentesis is done later, between 15 and 20 weeks, by collecting amniotic fluid. Both provide genetic material analyzed to determine if the fetus has inherited the trait or the full disease.
Interpreting Sickle Cell Test Results
Interpreting sickle cell test results involves looking at the specific combination and percentage of hemoglobin types found in the blood. The results are reported using abbreviations that represent the different forms of hemoglobin. Normal adult hemoglobin is denoted as HbA, while the sickling form is HbS.
A result showing only HbA (HbAA) indicates a normal status, meaning the individual has neither the disease nor the trait. Sickle Cell Trait is identified by the presence of both HbA and HbS (HbAS), where the amount of normal HbA is greater than the abnormal HbS. Individuals with the trait are healthy and do not experience disease symptoms, but they can pass the gene to their children.
A diagnosis of Sickle Cell Disease is confirmed when the test shows the presence of HbS without any HbA, which is the case for the most common and severe form, HbSS. Other forms of the disease, like Hemoglobin SC disease (HbSC) or Sickle Beta-Thalassemia (HbS/Beta-thalassemia), are identified by specific combinations of HbS with other abnormal variants.