Sickle Cell Disease
What is sickle cell disease?
Sickle cell disease (SCD) is an umbrella term for a group of genetic disorders affecting the body’s red blood cells.
People with SCD have atypical hemoglobin, a protein within red blood cells that helps circulate oxygen throughout the body – known as hemoglobin S or sickle hemoglobin – which causes their red blood cells to become misshapen. As a result, these red blood cells break down more quickly than usual and can block small blood vessels, cutting off the oxygen supply to certain tissues and causing complications.
SCD is typically a serious and lifelong condition, requiring long-term treatment and management. The disorder is most common in people of African, Caribbean, Middle Eastern, Eastern Mediterranean and Asian origin.
Subtypes of sickle cell disease
- HbSS (commonly known as sickle cell anemia)
- HbS beta-thalassemia
In all of these subtypes, “Hb” stands for “hemoglobin”. All sickle cell diseases are hereditary hemoglobinopathies, which means that a person has inherited genetic deformations of hemoglobin from one or both parents. Most of these subtypes don’t have “common” names and are therefore usually called by their abbreviations. The exception is sickle cell anemia.
HbSS, or sickle cell anemia, is the most common subtype of sickle cell disease. In this subtype, the affected person inherits one sickle-cell gene from each parent. This is called a homozygous sickle cell disease.
In HbSC, the affected person inherits a sickle-cell gene from one parent and a gene for a defective form of hemoglobin, hemoglobin-C, from the other.
HbS beta-thalassemia comes in two forms, beta 0-thalassemia, which is quite severe, and beta +-thalassemia, which is milder. These occur when the affected person has inherited a sickle-cell gene from one parent and a beta-thalassemia gene from the other.
HbSD, HbSE and HbSO are rarer subtypes of sickle cell disease. In these subtypes, the affected person has inherited a sickle-cell gene from one parent and a gene for a defective form of hemoglobin (Hemoglobin D, E or O) from the other. The severity of these subtypes varies.
Individuals who have only inherited a sickle-cell gene from one parent and no abnormal genes from the other have what is known as sickle-cell trait. In these cases, they are unaffected by the abnormal gene but may pass on a risk of sickle-cell disease to their children. If two people with sickle-cell trait have children, those children have a one in four chance of having sickle-cell disease, a one in four chance of being completely unaffected, and a one in two chance of being an unaffected carrier themselves.
Symptoms of sickle cell disease
The symptoms of SCD are typically intermittent, meaning they are experienced in episodes that come and go. Symptoms also tend to vary in frequency and severity from person to person and may change over time. They can occur in conditions that cause hypoxia, such as intense physical exertion.
Episodes of pain – also known as sickle cell crises – are one of the most common symptoms of SCD. The pain can vary in severity and may come on suddenly. Most often it is felt in the bones and joints, though it may also occur in other locations, such as the hands, feet, arms, legs or abdomen. Any area with both sensory nerves and blood supply can be affected during a painful episode. Many people with SCD experience chronic, low-level pain, often in bones and joints.
Painful episodes are caused by sickle-shaped cells blocking blood vessels and cutting off the oxygen supply to tissues. Although it is not clear what brings on these episodes, it is thought that changes in the weather, dehydration, stress and strenuous exercise can all act as triggers.
Acute chest syndrome
Acute chest syndrome occurs when blood vessels in the lungs become blocked, typically causing chest pain, a high temperature, coughing and shortness of breath. It should be treated as a medical emergency requiring urgent treatment. Symptoms of acute chest syndrome are:
- Chest pain, most common in adults.
- Shortness of breath, most common in adults.
- Fever, more common in children.
The cause of acute chest syndrome may be multifactorial and may include factors, such as:
- Blocked blood vessels.
- Shallow inhalation, which can lead to poor ventilation in the lung.
- Obstruction of blood supply (infarction) to the ribs.
People with SCD are susceptible to severe infection from certain types of bacteria. Common types of infection include:
- Blood infection (septicemia)
- Lung infection (pneumonia)
- Infection of the surroundings of the brain and the spine (meningitis)
- Bone infection (osteomyelitis)
Infection, particularly in infants, should be treated as a medical emergency requiring urgent treatment.
People with SCD will normally also experience mild to moderate anemia, a lack of hemoglobin. Periodically, however, this anemia can become severe and require urgent medical attention. This may occur suddenly or more gradually.
Signs and symptoms of the onset of severe anemia include:
- Shortness of breath
- Paleness, particularly in the eyelids, lips, tongue and fingernails
Signs and symptoms of sickle cell disease in infants
As a genetic disorder, SCD is present from birth, but will not generally begin to display symptoms until an infant is 5 to 6 months old. However, in some areas, routine newborn screening may find the disease.
Early signs and symptoms that may indicate the presence of SCD include:
- Swelling of the hands and feet that may cause pain (dactylitis)
- Fatigue, fussiness and irritability
- A yellowing of the skin and/or whites of the eyes (jaundice)
Causes of sickle cell disease
SCD is caused by a gene defect which creates atypical hemoglobin, known as hemoglobin S or sickle hemoglobin. Hemoglobin S behaves differently to normal hemoglobin, typically changing the shape of red blood cells from their usual spherical, donut-like shape, into a crescent or sickle-like shape. These deformed red blood cells tend to deplete faster than usual, causing anemia, and can block blood vessels, leading to a reduced supply of oxygen to the body’s tissues.
How is sickle cell disease inherited?
If an individual inherits one hemoglobin S gene and one normal hemoglobin gene from their parents, they will have something known as sickle cell trait and become a carrier of sickle cell disease. People with sickle cell trait, however, will generally be healthy and only rarely display signs or symptoms associated with SCD. These symptoms can occur during intense exercise or physical exertion.
If an individual inherits two hemoglobin S genes from their parents, that person may develop SCD. This may also be the case if an individual inherits one hemoglobin S gene plus another type of abnormal hemoglobin gene, such as thalassemia, hemoglobin C, hemoglobin D or hemoglobin E.
Diagnosing sickle cell disease
SCD is normally diagnosed following blood tests. To make the diagnosis, a blood sample will be taken and analysed in order to establish what type of hemoglobin is present. If the results prove inconclusive or there is any uncertainty, DNA tests may also be carried out.
Diagnosing sickle cell disease in newborn babies
In many places, tests for sickle cell disease are carried out on newborn babies as part of the routine postnatal screening process. To do this, a blood sample will be collected from a heel prick and sent to a laboratory for testing.
Parents will be informed of the results of the testing as soon as possible. If the results return positive for SCD, a second round of testing will be ordered to definitively confirm the diagnosis. If confirmed, parents will have treatment options thoroughly explained to them.
Postnatal tests will also be able to show whether or not a newborn has a sickle cell trait. This is important, as it may increase the chances of a sibling or the child’s future children inheriting the disorder.
Prenatal sickle cell disease diagnosis
Tests can also be carried out prior to birth to see whether a child will inherit SCD. This is usually done by using tissue from the placenta or amniotic fluid from the sac surrounding the embryo and can be carried out from around 8 to 10 weeks into the course of a pregnancy.
Sickle cell disease treatment
A number of treatment methods are available to manage the symptoms of SCD and prevent complications. However, in most cases, the disorder cannot be cured and will require lifelong management.
People with SCD will be treated by a specialist and will be required to attend check-ups at regular intervals. They will also be taught how to recognise the condition’s symptoms, so that treatment can be given as soon as possible after they appear.
Staying healthy is an important principle of managing SCD. This will often involve:[^10]
- Antibiotics: Taking daily doses of antibiotics (usually penicillin) is often recommended by doctors, particularly for children of five years of age or younger. This is aimed at preventing infection.
- Vaccinations: People with SCD, especially children, should ensure they keep up-to-date with all recommended vaccinations, including those against meningitis, influenza and hepatitis B.
- Vitamin supplements: Extra folic acid supplements are commonly recommended for people with SCD to aid the body in its production of red blood cells. A daily supplement containing zinc, Vitamins D, E, C and A, magnesium, selenium, carotenoids and flavonoids but not iron, may also be useful.
Treating painful episodes
Most mild to moderate painful episodes (sickle cell crises) will not require a visit to the hospital and can be treated at home. This may involve:
- Painkillers, usually paracetamol or ibuprofen
- Staying hydrated by drinking plenty of water
- Antibiotics. These are strongly recommended for children of younger than five, but are optional for older individuals. Should a fever develop, the individual should receive prompt medical attention regardless of whether or not they are on antibiotics.
If a painful episode is severe, professional medical attention should be sought as soon as possible. If fever appears, medical attention should be sought right away: fever is a medical emergency in people with SCD.
In people with frequent and severe pain resulting from SCD, hydroxyurea treatment is currently the standard. Hydroxyurea increases the concentration of functioning hemoglobin. This in turn reduces painful episodes and acute chest syndrome, as well as the need for hospitalisation and the number of blood transfusions a person with SCD may need.
A blood transfusion can be used to treat acute chest syndrome or severe anemia, as well as to prevent or treat certain complications. Blood transfusions, however, are not considered routine due to the complications they can cause, meaning they are only carried out when considered absolutely necessary.
Treatment to prevent clotting is recommended for all adults with SCD admitted to hospital.
Stem cell transplant
A stem cell transplant is the only known way to cure SCD. It does, however, come with the risk of severe complications, and its success is not guaranteed. It is generally reserved for very severe cases of SCD.
Erythrocytapheresis is a method of reducing hemoglobin concentration to less than 30%. In this procedure, red blood cells are removed from a blood sample, and the rest of the blood is introduced to circulation.
In this way, it cuts down the risk of stroke in adults and children from SBC. The treatment has relatively few side effects, all of which can be managed.
Sickle cell disease complications
There are various possible complications that can occur as a result of SCD.
Some of the most common complications related to SCD include:
- Growth and development problems
- Spleen problems
- Other complications (see below)
Growth and development problems
Children and adolescents with SCD may experience slowed growth and development. Teenagers may also undergo puberty two to three years later than average. Doctors will monitor childhood development closely and may suggest certain vitamin supplements to help manage possible problems.
Strokes are a common complication for children and adolescents with SCD and can occur in adults.
Sickle cells blocking blood vessels in the brain can shut off the oxygen supply, causing a stroke. Symptoms may include difficulty with speech and a weakness or paralysis of the face and limbs. In some cases, there may be no noticeable symptoms.
Strokes are generally treated with blood transfusions, which are able to improve blood flow to the brain.
If blood vessels in the spleen become blocked, the organ can swell with blood and cause a severe bout of anemia. This will often occur very suddenly and require urgent medical attention. In some cases, treatment may involve removing the spleen completely.
Other possible complications include:
- Heart, lung or kidney problems
- Eye or vision problems
- Unwanted and sustained erections (priapism)
- Leg ulcers
Sickle cell disease FAQs
Q: Can sickle cell disease be cured?
A: In the majority of cases, SCD cannot be cured. It can, however, be managed and its various complications treated as they occur. A possible cure for SCD is a stem cell transplant, though this is generally only reserved for very severe cases of the disorder, due to the risks associated with the procedure.
National Heart, Lung, and Blood Institute. “What Are the Signs and Symptoms of Sickle Cell Disease.” August 10, 2017. Accessed November 9, 2017. ↩
National Heart, Lung, and Blood Institute. “How is Sickle Cell Disease Diagnosed.” August 10, 2017. Accessed November 9, 2017. : Patient. “Sickle Cell Disease.” November 1, 2017. Accessed November 9, 2017. ↩
Tranfusion Medicine and Hemotherapy. “Erythrocytapheresis: Do Not Forget a Useful Therapy!”. Januiary 15, 2008. Accessed 4 May, 2018. ↩