Sickle cell anemia, also commonly known as sickle cell disease (SCD), is a genetic health condition that is characterized by the production of hemoglobin S (Hgb S or HB S), an irregular type of hemoglobin. Hemoglobin is the iron-rich protein found in red blood cells that is responsible for transporting oxygen from the lungs to other parts of the body and releasing it to various body cells and tissues.
Hemoglobin is composed of heme, which is the part that contains iron and globin chains, which are rich in proteins.
Globin chains are simply blocks of amino acids that form protein compounds. There are different variants of globin chains, namely gamma, delta, beta, and alpha. Regular hemoglobin variants are:
- Hemoglobin A (Hb A): comprises about 96% of hemoglobin in adults; it is made up of two beta protein chains and two alpha chains.
- Hemoglobin A2 (Hb A2): comprises about 2.5% of hemoglobin in adults; it is made up of two delta and two alpha protein chains.
Hemoglobin F (fetal hemoglobin, Hb F): comprises about 1.5% of hemoglobin in adults; it is made up of two gamma and two alpha protein chains. This is the main hemoglobin variant produced by a fetus during pregnancy. Immediately after birth, Hb F is replaced by Hb A as the main hemoglobin variant in the body.
Other types of hemoglobin – these come from either non-alpha or alpha (delta, gamma, or beta) globin chains gene mutations. Currently, there are hundreds of hemoglobin variants that have been discovered and documented.
Hemoglobin Hb E, Hb D, Hb C, and Hb S, resulting from gene mutations of beta-globin chains, are some common types of hemoglobin variants.
Hb S arises from a gene mutation that alters the beta chain of hemoglobin. This gene mutation can alter either one of the beta chains of hemoglobin A (HS trait or heterozygote status) or both (sickle cell anemia and homozygote status)
An individual with one regular hemoglobin gene copy and one Hb S copy will have above 40% Hb S but will produce about 60% Hb A which is enough to prevent any health problems. This single altered copy (heterozygous) can be genetically passed on to offspring.
When an individual has two copies of the altered gene (homozygous), the individual produces about 85% Hb S, no regular Hb A, and has sickle cell disease or sickle cell anemia. Signs and symptoms of sickle cell anemia may also be experienced by individuals who have one sickle cell gene copy and one gene copy for another type of hemoglobin (doubly heterozygous), like Hb C or hemoglobin types observed with thalassemia, a classification of blood disorders that arise from gene mutations that affect regular hemoglobin production. Individuals with two copies of the Hb S gene (SS), and those with one copy and a hemoglobin type (SOArab, SD, S beta-thalassemia, SC), are all classified as suffering from sickle cell anemia.
The Hb S mutation produces hemoglobin that is less soluble in red blood cells. This decreases the efficiency of oxygen exchange and can result in the formation of polymers within the cell during regular oxygen flow. These polymers can alter the shape of a red blood cell from a round disc to a sickle shape, especially in low oxygen environments. The altered shape affects the red blood cell’s ability to move smoothly through the bloodstream. The affected ‘sickled’ cells get stuck in the bloodstream and block small blood vessels leading to unwanted consequences.
Sickled red blood cells have very short lifespans of about 15 days as opposed to 120 days of healthy red blood cells. To compensate, people with sickle cell anemia must produce more RBCs and release them into the bloodstream faster and earlier than normal. These individuals subsequently become anemic when their bodies cannot keep up with the normal production rate of RBCs, resulting in a disorder called hemolytic anemia, tinier red blood cells (microcytosis), and a higher number of newly formed RBCs known as reticulocytes (reticulocytosis).
The National Blood, Lung, and Heart Institute recently reported that close to 100,000 people in the United States suffer from sickle cell disease. It affects roughly one in every 365 African Americans. An estimated one in every 13 African Americans have the sickle cell gene trait. Other groups affected by this condition include Asian-Indians, Middle Easterners, South Europeans, and Hispanics.
Signs and Symptoms
Sign and symptoms of sickle cell anemia, as well as their severity, vary extensively in the global population. While some people may experience acute symptoms, others may experience very severe symptoms that cause harsh complications. Young children with sickle cell anemia are usually healthy at birth but proceed to develop initial symptoms in their first year as Hb F replaces Hb S as the predominant hemoglobin variant.
Individuals with sickle cell anemia as a result of having two mutated gene copies of Hb S (SS) are more likely to experience severe symptoms that those with one mutated gene copy of Hemoglobin C (SC), or Hemoglobin S (AS). Individuals with sickle cell trait are usually healthy but may experience sickle cell disease symptoms when they have low oxygen levels in their body due to factors such as changes in altitude, intense exercise, dehydration, and many others.
Long periods of pain are a common symptom of sickle cell anemia. The pain is caused by the narrowing or blocking of small blood vessels (vaso-occlusion), which prevent blood from flowing to the affected areas and can lead to tissue damage. The affected area and the duration of pain can vary from case to case and can happen anywhere in the body, especially in the belly, lungs, joints, and bones. Swelling and pain in the feet and hands are often one of the initial symptoms observed in infants. Extreme temperatures, changes in altitude, dehydration, infection, and reduced oxygen levels can trigger the pain crises. However, most crises occur without any observable trigger. A typical pain crisis may take some days or a few weeks to resolve. Some individuals with sickle cell anemia may suffer from one pain crises every few years, while others may experience several crises in a year.
- Anemia is a common complication of this condition due to the shorter lifespan of red blood cells. Those affected may experience an increased heart rate, shortness of breath, paleness, dizziness, reduced stamina, and fatigue. Anemic children may develop at a slower rate than normal children. An aplastic crisis may happen when the production of red blood cells is disrupted. The main cause of low red blood cell production among people with sickle cell anemia is a parvovirus B19 infection. This infection specifically affects the production of red blood cells in the bone marrow.
- Higher risk of infections, such as respiratory infections, can be severe in people who suffer from sickle cell anemia. The Center for Disease Control (CDC) notes that pneumonia is the main cause of death among young children who suffer from sickle cell anemia.
- Acute chest syndrome, caused by vaso-occlusion, is a respiratory injury that is characterized by symptoms such as fever, chest pain, and coughing. The condition can develop fast and become fatal.
- Stroke is one of the most severe complications of sickle cell disease as it can cause disability and permanent body damage. A stroke occurs in about 10% of children who suffer from sickle cell disease. This complication is more common in children than adults,
- Splenic sequestration occurs when sickle cells get trapped in the spleen leading to blockage and inflammation. Primarily observed in children, splenic sequestration can cause symptoms such as weakness, nausea, and abdominal pain that can progress to shock. This condition can be fatal and may require surgical intervention.
- Enlarged liver characterized by scleral icterus (yellowing of the eyes) and jaundice.
- Enlargement of the bone marrow and the possibility of deformation in bones involved in the production of red blood cells.
- Other complications of sickle cell anemia include sustained erection (priapism), nutritional and caloric deficiencies (zinc, folic acid), disease of the retina in the eye (retinopathy), leg ulcers, bone necrosis (tissue death), and gallstones. Kidney disease is a common complication of sickle cell disease that affects older patients who are above 40 years. 60% of these patients suffer from proteinuria and renal failure.
Tests
The objectives of sickle cell tests are to identify individuals with sickle cell trait, to diagnose sickle cell disease as early as possible, and to identify, analyze and treat sickle cell disease complications when they occur. Infant screening for sickle cell is now done routinely throughout the United States. This screening can identify different types of hemoglobin present in infants through blood samples taken using heel sticks.
Sickle cell tests include:
Sodium metabisulfite test and hemoglobin solubility test for sickle cell disease.
Hemoglobinopathy (Hb) evaluation via hemoglobin HPLC, hemoglobin isoelectric focusing, or hemoglobin electrophoresis to identify irregular hemoglobin variants in red blood cells; the test can be done after a blood transfusion to ensure that an adequate amount of regular hemoglobin is present to lower the risk of damage from red blood cell sickling.
Genetic testing-DNA analysis to analyze gene mutations that encode hemoglobin components (beta-globin); DNA testing may also be employed to find if an individual is a carrier of sickle cell disease. This gene testing can also be performed prenatally, either by analyzing the DNA of the fetal cells found in the amniotic fluid via amniocentesis or by evaluating cell-free fetal DNA isolated from the maternal circulation.
Other tests may include:
Complete blood count (CBC) is used to determine the quantity and size of red blood cells in the body as well as how much hemoglobin they have, both of which are often very low in people suffering from sickle cell anemia.
Iron studies to analyze the body’s iron levels, which can be higher in people with sickle cell anemia who have already undergone several blood transfusions.
Bilirubin is used to diagnose individuals suspected of having gallstones or jaundice, as well as an extra test for analysis of hemolytic anemia.
Creatinine test to look for elevated levels of creatinine in the blood that show irregular kidney function in a bid to find any indicators of development of kidney disease.
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