Sickle Cell Tests
Also known as:Hemoglobin S; Hb S; Hgb S
Formal name:Hemoglobin S Evaluation
Related tests:Hemoglobin Electrophoresis; Hemoglobin Isoelectric Focusing; Hemoglobin S Solubility; Hemoglobin Fractionation by HPLC; Hemoglobinopathy Evaluation; Complete Blood Count; Blood Smear; Iron Tests
Why Get Tested?
To determine if you have sickle cell trait or disease by measuring the presence and relative amount of hemoglobin S
When to Get Tested?
Routinely as part of a newborn screen or whenever it is necessary to determine whether someone is a sickle cell carrier or has sickle cell anemia, particularly in the African American population
A blood sample drawn from a vein in your arm or obtained from the heel or finger of an infant
Test Preparation Needed?
None; however, if this test is used for diagnosis, the sample should not be drawn after a recent blood transfusion.
How is it used?
Sickle cell tests are used to identify the presence of hemoglobin S, to evaluate the status and number of a person's red blood cells (RBCs) as well as hemoglobin level, and/or to determine whether a person has one or more altered hemoglobin gene copies. The presence of other abnormal hemoglobin variants may be seen but would require additional testing to identify specifically what type.
There are almost 900 hemoglobin variants of which hemoglobin S is one. To screen for and to confirm the presence of hemoglobin S, a variety of tests have been developed. Some of these tests are:
Screening may be performed on family members of an individual who has sickle cell trait/disease. It also may be done for those who were not screened at birth because universal newborn testing was not yet implemented and who may choose to be tested if their status is not known.
- Hemoglobin S solubility test and sodium metabisulfite test. Both tests are used to screen for hemoglobin S by adding certain chemicals to a patient's blood sample that reduce the amount of oxygen present. The reduced amount of oxygen will cause the abnormal sickle-shaped cells to form. Some hemoglobin S will be present in those who carry one sickle cell gene (sickle cell trait) and much more will be present in those who have sickle cell disease. This test detects the presence of hemoglobin S but does not distinguish between sickle cell disease and trait. It should not be performed on infants until they are at least 6 months old because of the presence of hemoglobin F as the predominant hemoglobin at birth. Infants with sickle cell disease or trait will not produce significant amounts of hemoglobin S until several months after birth; therefore, this test may give a false-negative result if performed too early (if hemoglobin S is <10%).
For Screening, Diagnosis, and Confirmation:
- Hemoglobinopathy (Hb) evaluation. There are several methods of evaluating the type and relative amounts of various normal and abnormal hemoglobin types. These methods typically separate the different types of hemoglobin that are present so that they can be identified and quantified. They include:
- Hemoglobin electrophoresis, traditionally used as the method to identify the presence of various hemoglobins
- Hemoglobin fractionation by HPLC, the most frequently used method to screen for hemoglobin variants, including Hb S
- Isoelectric focusing, a highly sensitive method that is often used at large reference laboratories
- Newborn screening for sickle cell is now mandated by all 50 states in the U.S. and the District of Columbia. It is performed via the more sensitive Hb isoelectric focusing or HPLC fractionation and identifies the specific types of hemoglobin present. As an infant with sickle cell trait/disease grows and develops, the amount of Hb S will increase as the amount of hemoglobin F decreases. At about age 2, the levels stabilize.
- DNA analysis. This test is used to investigate alterations and Mutations in the genes that produce hemoglobin components. It may be performed to determine whether someone has one or two copies of the Hb S mutation or has two different mutations in hemoglobin genes (e.g., Hb S and Hb C). Genetic testing is most often used for prenatal testing: amniotic fluid may be tested at 14 to 16 weeks to provide a definitive answer. Genetic counseling is strongly encouraged if a positive sickle screen from one or both parents is determined. It can also be performed earlier with chorionic villus sampling.
For Monitoring Treatment:
Particularly in people with sickle cell disease, the relative amount of Hb S will be measured and followed over the course of treatment, for example, after a blood transfusion to ensure that the hemoglobin S level has been reduced.
Other tests that may be used to help evaluate someone who is suspected of having or who is known to have sickle cell trait or disease include:
- complete blood count (CBC). The CBC is a snapshot of the number of cells in the bloodstream. Among other things, the CBC indicates how many red blood cells are present and how much hemoglobin is in them and will evaluate the size and shape of the RBCs present. This test is used to detect anemia.
- Blood Smear (also called peripheral smear and manual differential). In this test, a trained laboratorian looks at a thin, stained layer of blood on a slide under a microscope. The number and type of red blood cells are evaluated to see if they are normal. Sickle-shaped RBCs may be seen on the blood smear.
- Iron studies. These may include: iron, ferritin, UIBC, TIBC, and transferrin saturation. These tests measure different aspects of the body's iron storage and usage. They are ordered to help determine whether someone has an iron deficiency anemia or an excess amount of iron (iron overload). People with sickle cell anemia who receive multiple blood transfusions may experience an iron overload.
When is it ordered?
Sickle cell tests are routinely ordered to screen newborns for sickle cell anemia. All 50 states in the U.S. and the District of Columbia now require screening for newborns.
Testing may be done when those who were born before newborn screening was mandated want to know if they have sickle cell disease or are carrying the sickle cell trait, especially if they are in a high-risk group. It has been estimated that one out of every 500 African Americans has sickle cell anemia.
One or more sickle cell tests may be done to help diagnose someone who has not previously been tested when the person has symptoms and/or complications of the disease such as:
- Pain due to sickle cell crises. The most common symptoms of sickle cell disease are episodes of pain that can last for extended periods of time. The pain can occur throughout the body and often involves the bones, joints, lungs, and stomach.
- Anemia. Sickle cell disease is a hemolytic anemia, meaning that the abnormal, sickled RBCs break down (hemolyze) more quickly than normal red blood cells and cannot be replaced by the body as quickly as needed, thus leading to a decreased number of RBCs and reduced ability of the RBCs to transport oxygen throughout the body.
- Increased number and frequency of infections, especially pneumonia, which is the leading cause of death in children with sickle cell disease.
- Coughing, chest pain, and fever suspected to be caused by a serious complication of sickle cell disease called acute chest syndrome.
Other symptoms may include retina damage and vision loss, growth problems in children, leg ulcers in the lower part of the leg, gallstones, and painful extended erections of the penis called priapism. Because sickled RBCs do not easily flow throughout the body due to their characteristic sickle shape, they can become trapped in various areas and cause serious complications. These can include splenic sequestration (a rapid enlargement of the spleen), damage to organs, tissues, or bones due to a lack of blood flow (such as to the kidneys) or stroke, which occurs in 10% of children affected by sickle cell disease.
What does the test result mean?
In newborns who carry the sickle cell gene, fetal hemoglobin F will predominate but a small amount of hemoglobin S will also be present. There may be a small amount of hemoglobin A if they have sickle cell trait. A full work-up should be done after the child reaches six months of age.
Adults with sickle cell trait will produce mostly normal hemoglobin A, while those with sickle cell disease (anemia) will produce mostly Hb S with no Hb A. People who are heterozygous for two different hemoglobin variants will usually produce varying amounts of both types. For example, they may produce both Hb S and Hb C but no Hb A.
If two copies of the Hb S gene mutation are detected, then the person has sickle cell disease. If the person has one gene that codes for Hb S and one normal gene, then the person has sickle cell trait. If the person has one Hb S copy and a Hb C or beta thalassemia mutation, then the person is likely to experience some symptoms and complications associated with sickle cell disease. If the person has one Hb S gene copy and another, more rare hemoglobin variant, then the person may or may not have any symptoms or complications. See the article on Hemoglobin Abnormalities for more on this.
Is there anything else I should know?
Sickle cell anemia symptoms and the complications experienced will vary greatly from person to person, even within the same family.
Recent blood transfusions, typically within the last three months of the date of testing, may cause a false-negative test result with some of the tests (e.g., Hb S solubility tests) because transfusion of normal RBCs reduce the relative amount of hemoglobin S present in an affected person's system.
People with sickle cell trait are generally healthy, but those who exercise heavily, such as athletes and those who are exposed to dehydration or altitude extremes, may sometimes experience sickle cell anemia symptoms. Sickle cell carriers produce both Hb A and some Hb S. When they are subjected to significant stresses that reduce the amount of oxygen in the body, the RBCs that contain Hb S can sickle.
What is being tested?
Sickle cell tests are used to help diagnose sickle cell anemia (also called sickle cell disease) and to identify those who may have sickle cell trait. Sickle cell anemia is an inherited disorder that leads to the production of an abnormal hemoglobin called hemoglobin S (Hb S or Hgb S). Sickle cell tests determine the presence and relative amount of hemoglobin S in a blood sample.
Hemoglobin is a protein found in red blood cells (RBCs) that binds to oxygen in the lungs and carries it to tissues throughout the body. Typically, hemoglobin A (Hb A, adult hemoglobin) makes up most of the hemoglobin found in normal RBCs in adults, with small amounts of hemoglobin A2 and hemoglobin F. Before babies are born, they normally produce large amounts of hemoglobin F (Hb F, fetal hemoglobin), which is then replaced by Hb A as the predominant hemoglobin shortly after birth.
Mutations in the genes that code for the production of hemoglobin can lead to abnormal types of hemoglobin (variants). Common mutations include the mutations causing beta thalassemia, a blood disorder that results in reduced production of hemoglobin, and mutations associated with hemoglobin variants such as Hb S and hemoglobin C (Hb C). With a normal hemoglobin gene copy from one parent and a Hb S gene copy from the other parent (heterozygous), a person is said to have sickle cell trait and to be a sickle cell carrier. When someone has two Hb S gene copies (one from each parent; homozygous), then the person has sickle cell anemia (disease). If the person has one Hb S gene and one other abnormal gene, such as a Hb C gene, then the person will experience some of the same symptoms associated with sickle cell disease.
Hb S can form crystals that change the shape of the RBC from a round disc to a characteristic sickle shape. This altered shape limits the RBC's ability to flow smoothly throughout the blood vessels in the body, limits the hemoglobin's ability to transport oxygen to tissues, and decreases RBC lifespan from 120 days to about 10-20 days. A person with sickle cell disease (homozygous for Hb S) can become severely anemic because the body cannot produce RBCs as fast as they are destroyed. The affected person can suffer painful episodes and a variety of complications when sickled cells become lodged in and obstruct small blood vessels (vaso-occlusion).
Sickle cell tests are done to determine whether someone is producing hemoglobin S and thus carrying a sickle gene. They are ordered routinely as part of newborn screening programs and are mandated by every state in the U.S. and the District of Columbia. If results of a newborn screen are abnormal, then one or more sickle cell tests may be ordered to confirm abnormal findings. Sickle cell tests may also be ordered along with or following an abnormal complete blood count (CBC) and Blood Smear to help evaluate someone who has an unexplained hemolytic anemia or who demonstrates symptoms that suggest the presence of sickle cell anemia.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm or, for infants, by pricking a heel or finger.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed; however, testing for diagnosis should not be performed after a recent blood transfusion.
- Who is at risk for sickle cell disease?
Anyone can inherit Hb S gene mutations, but sickle cell disease is more prevalent among those of African ancestry and those who can trace their roots to the Mediterranean area, South and Central America, the Middle East, India, and the Caribbean.
- Why is this pattern of prevalence seen?
It mirrors the areas of the world where malaria is found. Historically, sickle cell offered some protection and survival advantage against malaria. Since people from these areas have moved throughout the world, sickle cell gene mutations have become more widespread. It has been noted that the rates of sickle cell anemia are increasing worldwide and are projected to affect more than 400,000 newborns by 2050, with India and sub-Saharan Africa showing the sharpest increases.
- Why would an athlete be tested for sickle cell trait?
Newborn screening identifies most cases of sickle cell trait and sickle cell anemia. However, this screening was not universally performed in the U.S. until relatively recently. Many adults, and especially athletes born in other countries, may not have been tested to determine their sickle cell status. Since there is some risk of "exertional sickling" during intense training, the National Collegiate Athletic Association (NCAA) advocates testing college athletes who have not documented their sickle cell status.
© 2017 American Association for Clinical Chemistry, republished from Lab Tests Online.*
Descriptions of clinical laboratory tests were originally prepared for use on Lab Tests Online, an award-winning patient education website on clinical laboratory testing. Lab Tests Online is produced by the American Association for Clinical Chemistry (AACC), a global scientific and medical professional organization dedicated to clinical laboratory science and its application to healthcare. The Lab Tests Online website is developed in collaboration with other laboratory professional societies and is funded in part through corporate sponsorships.