Brief overview
- Description: Hereditary disease in which the red blood cells (erythrocytes) become sickle-shaped
- Causes: Sickle cell anemia is caused by a defective gene that is responsible for the formation of hemoglobin (red blood pigment).
- Prognosis: Sickle cell anemia varies in severity. The earlier the symptoms are treated, the better the prognosis. If left untreated, the disease is usually fatal.
- Symptoms: Severe pain, circulatory disorders, anemia, frequent infections, organ damage (e.g. spleen), strokes, growth retardation
- Diagnosis: consultation with the doctor, physical examination, blood test, ultrasound, CT, MRI
What is sickle cell disease?
Sickle cell disease (SCD) – also known as sickle cell disease or drepanocytosis – is a hereditary disease. In this disease, healthy red blood cells (erythrocytes) change into abnormal, sickle-shaped cells (sickle cells). Due to their shape, these can block blood vessels in the body. Typical symptoms of the disease are severe pain, circulatory disorders, anemia and organ damage.
The disease belongs to the group of hemoglobinopathies. These are various disorders of the red blood pigment haemoglobin.
Doctors prefer the term sickle cell disease instead of sickle cell anemia, as not all forms are accompanied by anemia. In addition, the disease does not focus on anemia as a symptom, but on the symptoms that trigger the vascular occlusions.
How common is sickle cell anemia?
Who is particularly affected?
Sickle cell anemia mainly affects people from Central and West Africa. It initially occurred mainly in the sub-Saharan part of the African continent. However, due to migration, sickle cell disease has now spread worldwide. Today, many people from parts of the Mediterranean, the Middle East, India and North America are also affected.
Since the 1960s, sickle cell disease has also been widespread in Northern Europe (e.g. Germany, Austria, France, England, the Netherlands, Belgium and Scandinavia).
Sickle cell anemia and malaria
This gives people who have a healthy and a diseased gene (so-called heterozygous gene carriers) a survival advantage (heterozygote advantage) in the regions where malaria is spreading. This also explains why a relatively large number of people there suffer from sickle cell anemia.
How does sickle cell anemia develop?
Sickle cell anemia is a hereditary disease. It is caused by an altered gene (mutation) that the father and mother pass on to their child. The genetic defect changes healthy red blood pigment (haemoglobin; Hb for short) into abnormal sickle cell haemoglobin (haemoglobin S; HbS for short).
Congenital genetic defect
Red blood cells normally consist of “healthy” haemoglobin, which is made up of two protein chains – the alpha and beta chains. These chains make the blood cells round and smooth, allowing them to pass through every tiny blood vessel and supply all organs with vital oxygen and nutrients.
In sickle cell anemia, genetic errors (mutations) cause the so-called beta chain of haemoglobin to be abnormally altered (haemoglobin S). If there is too little oxygen in the blood, the shape of the sickle cell haemoglobin changes and with it that of the red blood cells.
Due to their shape, sickle cells are much more immobile and die earlier than healthy red blood cells (haemolysis). On the one hand, this causes anemia in the body (so-called corpuscular hemolytic anemia) because the affected person has too few red blood cells. On the other hand, the sickle cells block smaller blood vessels more easily due to their shape.
This means that the affected areas of the body are no longer adequately supplied with oxygen. As a result, the tissue can die and, in the worst case, the organs can no longer fulfill their vital function.
How is sickle cell disease inherited?
It has different effects whether the child inherits only one pathological gene or both genes:
Homozygous gene carrier
If both the father and the mother carry the altered gene and both pass it on to their child, the child carries two altered genes (homozygous gene carrier). The child will develop sickle cell anemia. In this case, the child only produces abnormal hemoglobin (HbS) and no healthy hemoglobin (Hb).
Heterozygous gene carrier
Doctors also advise carriers of the disease to seek advice beforehand regarding the possible inheritance and associated risks for the child if they wish to have children.
Is sickle cell disease curable?
The prognosis of sickle cell disease depends heavily on how well and early the symptoms and complications are treated. Around 85 to 95 percent of all children with sickle cell disease reach adulthood in countries with good healthcare (e.g. Europe, USA). The average life expectancy is then around 40 to 50 years. In countries with poorer medical care, mortality is higher.
How does the disease progress?
Some people with sickle cell disease have hardly any symptoms, while others suffer greatly from the consequences of the disease. It is not yet clear why the disease progresses so differently.
People with sickle cell disease usually show the first signs of the disease as an infant.
What forms of sickle cell disease are there?
There are different forms of sickle cell disease. These develop depending on how the gene responsible for the formation of the red blood pigment is altered. All forms are inherited. However, the respective forms progress differently and the symptoms also vary in severity.
Sickle cell disease HbSS (SCD-S/S)
SCD-S/S is the most common form of sickle cell anemia. It is the most severe form. Those affected have inherited an altered gene from both parents. They therefore only produce the pathologically altered sickle cell haemoglobin (HbS).
Sickle cell disease HbSß-Thal (SCS-S/beta-Thal)
In SCS-S/beta-Thal, children inherit the sickle cell gene from one parent and a gene for beta-thalassemia from the other. The latter is another blood disorder in which the body produces too little or no hemoglobin. This form of sickle cell disease is rarer and usually has a milder course.
Sickle cell disease HbSC (SCD-S/C)
Sickle cell disease develops not only when a child inherits two sickle cell genes, but also when the parents pass on a sickle cell gene combined with another pathologically altered hemoglobin gene (such as the HbC or thalassemia gene).
What are the symptoms?
The symptoms of sickle cell anemia usually affect the entire body. In principle, it is possible for the sickle cells to block every blood vessel in the body. The most common symptoms of sickle cell disease are
Severe pain
Changes in the weather, lack of fluids, infections with fever and exhaustion often trigger this pain. Older people with sickle cell anemia are also more often affected by severe pain crises than children.
For some people with sickle cell anemia, the pain only lasts a short time, while others often spend a long time in hospital and need painkillers.
Anemia
Organ damage
Because the blood vessels are blocked by the sickle cells, the affected areas of the body are no longer adequately supplied with blood (so-called sickle cell crises). As a result, the tissue receives too little oxygen and nutrients, causing it to die over time. The affected organs are then no longer able to function properly.
This usually affects the bone marrow, the lungs, the brain, the spleen and the gastrointestinal tract.
Infections
Infections with fever are an emergency for people with sickle cell disease! Therefore, if your body temperature exceeds 38.5 degrees Celsius, consult a doctor immediately!
Hand-foot syndrome
Young children often experience pain, redness and swelling of the hands and feet due to vascular occlusion (hand-foot syndrome). This is often the first sign that the child is suffering from sickle cell anemia.
Growth retardation
The lack of oxygen in the tissue can lead to delayed growth in children. The onset of puberty may also be delayed. However, affected children usually catch up by the time they reach adulthood.
Bone necrosis
Ulcers
It is also possible that sickle cells clog the blood vessels in the skin (especially on the legs), which means that the tissue is no longer supplied with sufficient nutrients. As a result, those affected often have painful, open wounds on their legs (ulcers), which are usually difficult to heal.
Visual impairment and blindness
If the sickle cells block blood vessels in the retina of the eye, the surrounding tissue dies and scars form at the back of the eye. This impairs the vision of those affected and, in the worst case, can lead to blindness.
Gallstones, jaundice
Haemolytic crisis, aplastic crisis
In sickle cell disease, the sickle-shaped altered red blood cells are broken down more quickly. Triggered by infections, for example, there is a risk of haemolytic crises in which masses of red blood cells break down. If no more red blood cells are produced at all, doctors speak of an aplastic crisis. Those affected require immediate medical treatment! A blood transfusion is often necessary to prevent a life-threatening lack of oxygen and cardiovascular failure.
Spleen sequestration and splenomegaly
Spleen sequestration usually develops over one to three days. Symptoms include fever and abdominal pain. Those affected are also often pale and listless, similar to a cold. The spleen swells up due to the large amount of blood that accumulates. This can be felt in most cases.
It is important that parents of babies and toddlers with sickle cell anemia learn to palpate their child’s spleen. If the spleen is enlarged, doctors advise parents to take their children to hospital immediately.
Acute thoracic syndrome (ATS)
The symptoms of acute chest syndrome are similar to those of pneumonia: Those affected (often children) have a fever, cough, difficulty breathing and severe chest pain, especially when breathing. If the chest syndrome occurs repeatedly, this damages the lungs in the long term.
If those affected carry out regular breathing exercises and/or respiratory therapy, it is possible to prevent acute chest syndrome. This involves the patient learning exercises (e.g. stretching exercises) and techniques that make breathing easier.
If there are signs of acute chest syndrome, it is important to take the patient to hospital immediately!
Stroke
Signs of a stroke include a sudden headache, sudden numbness or weakness in one side of the face, arm or leg or even the whole body, speech disorders or a seizure.
If the patient shows signs of a stroke, call an emergency doctor immediately!
When to see a doctor?
Certain symptoms in people with sickle cell anemia indicate serious, sometimes life-threatening complications. It is therefore advisable to see a doctor immediately if:
- Sick people have a fever above 38.5 degrees Celsius
- they are pale and listless
- they have chest pain
- they are short of breath
- they have joint pain
- the spleen is palpable and enlarged
- those affected suddenly develop yellow eyes
- they excrete very dark urine
- they have a headache, feel dizzy and/or experience paralysis and sensory disturbances
- the penis is persistently and painfully stiff (priapism)
How is sickle cell disease treated?
Once the doctor has diagnosed sickle cell disease, it is important that the affected person is treated by a specialized treatment team that works closely with family doctors and paediatricians. In this way, the patient receives the best possible treatment.
Hydroxycarbamide
Doctors usually treat patients with sickle cell disease with the active ingredient hydroxycarbamide (also known as hydroxyurea). This is a cytostatic drug that is also used to treat cancer. This medication makes the blood more fluid and increases the fetal haemoglobin (HbF) in the body. Fetal hemoglobin is found in healthy newborns and inhibits the formation of sickle cells.
If people with sickle cell anemia take hydroxycarbamide regularly, pain crises occur less frequently. The drug also increases the red blood pigment haemoglobin in the blood, which makes patients feel better overall.
Painkiller
People with sickle cell anemia should not take acetylsalicylic acid (ASA). This active substance increases the risk of severe brain and liver damage.
Blood transfusion
Doctors prescribe blood transfusions to patients with sickle cell anemia in the event of strokes or to prevent strokes, as well as in the event of spleen sequestration and acute chest syndrome. These are given regularly (usually monthly) and often for life.
Vaccinations
To prevent life-threatening infections, doctors vaccinate young children with sickle cell disease against pneumococci (bacteria that cause pneumonia) as early as the second month of life. Other special vaccinations that doctors recommend for sickle cell disease are vaccinations against meningococci (meningitis), Haemophilus (croup, pneumonia, meningitis, joint inflammation), influenza viruses and hepatitis viruses.
Antibiotics
If patients with sickle cell anemia suffer from gallbladder inflammation, an ulcer or an infectious disease, doctors also administer antibiotics.
Stem cell transplantation
A stem cell transplant (bone marrow transplant) enables doctors to cure people with sickle cell disease.
However, stem cell transplantation is associated with risks and is not suitable for everyone with sickle cell disease. It is therefore only performed on patients with a very severe course of the disease.
How does stem cell transplantation work?
The doctors then administer the healthy stem cells to the patient with the help of a blood transfusion. In this way, they replace the diseased bone marrow with healthy stem cells and the affected person now produces new, healthy blood cells themselves.
In order for the recipient’s body to accept the donor’s new stem cells, the blood must match in most characteristics. This is why doctors prefer to use siblings as donors, as they often have the same characteristics (HLA genes).
Gene therapy
So far, however, there has only been experience with individual patients. Further studies are needed to clarify the extent to which gene therapy can be used as a treatment method for sickle cell disease.
Other therapies
The treatment of people with sickle cell disease is constantly evolving. It is therefore important that patients and their relatives keep themselves regularly informed about the latest therapies.
How does the doctor make the diagnosis?
The first point of contact if sickle cell disease is suspected is usually the pediatrician. If necessary and for further examinations, they will refer you to an internal medicine specialist with a specialization in blood diseases (haematologist).
As sickle cell anemia is a hereditary disease, the family history provides initial clues. For example, the doctor will ask whether there are any known carriers of the disease in the family.
Doctors also advise older children and adolescents from risk areas who have anemia and frequent severe pain or infections to be tested for sickle cell disease. If there are indications of the disease, the doctor will carry out a blood test.
Blood test
To diagnose sickle cell anemia, the doctor carries out a blood test. The typical sickle-shaped red blood cells can usually be seen directly in the blood smear under a microscope. To do this, he takes a drop of blood from the affected person and spreads it on a slide (e.g. on glass). If no sickle cells can be seen, however, this does not mean that there is no sickle cell disease.
If, for example, abnormal haemoglobin (HbS) is found that makes up less than 50 percent of the total haemoglobin in the blood, the patient is a carrier of the disease. If the affected person has more than 50 percent HbS in the total haemoglobin, they probably have sickle cell anemia.
Molecular genetic tests
Further examinations
In order to prevent symptoms of sickle cell disease or to prevent possible complications at an early stage, the following examinations are also possible:
- Examination of the child in the womb before birth (prenatal diagnostics)
- Regular check-ups in specialized centers
- Blood and urine tests
- Examination of the cerebrospinal fluid (CSF)
- Determination of the blood group if a blood transfusion is necessary
- Ultrasound of the abdomen and heart
- Ultrasound of the blood vessels in the brain (e.g. if a stroke is suspected)
- X-rays of the lungs, bones or joints
- Computed tomography (CT) or magnetic resonance imaging (MRI)
