Sickle Cell Disease (Sickle Cell Anemia) Causes, Types, Symptoms, Diagnosis, Treatment, Prevention

Sickle Cell Disease (Sickle Cell Anemia) Causes, Types, Symptoms, Diagnosis, Treatment, Prevention


What Is Sickle Cell Disease (Sickle Cell Anemia)?


Sickle cell disease  (Sickle cell anemia) is a disorder of the blood caused by an inherited abnormal hemoglobin (an oxygen-carrying protein within the red blood cells). The abnormal hemoglobin causes distorted (sickled) red blood cells. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. This condition is referred to as Sickle cell disease. The irregular sickled cells can also block blood vessels causing tissue and organ damage and pain.

Sickle Cell Disease (Sickle Cell Anemia) Causes, Types, Symptoms, Diagnosis, Treatment, Prevention


Normally, red blood cells are round and flexible so they can travel freely through the narrow blood vessels. The hemoglobin molecule has two parts: an alpha and a beta. Patients with sickle cell disease have a mutation in a gene on chromosome 11 that codes for the beta subunit of the hemoglobin protein. As a result, hemoglobin molecules don't form properly, causing red blood cells to be rigid and have a concave shape (like a sickle used to cut wheat). These irregularly shaped cells get stuck in the blood vessels and are unable to transport oxygen effectively, causing pain and damage to the organs.

Sickle cell disease is one of the most common inherited blood anemias. The disease primarily affects Africans and African Americans. It is estimated that in the United States, some 50,000 African Americans are afflicted with the most severe form of Sickle cell disease. Overall, current estimates are that one in 1,875 U.S. African American is affected with Sickle cell disease.

How is Sickle Cell Disease (Sickle Cell Anemia) inherited?


Sickle cell disease is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition whereas sickle cell trait is inherited as an autosomal dominant trait. This means that the gene can be passed on from a parent carrying it to male and female children. In order for Sickle cell disease to occur, a sickle cell gene must be inherited from both the mother and the father, so that the child has two sickle cell genes.

The inheritance of just one sickle gene is called sickle cell trait or the "carrier" state. Sickle cell trait does not cause Sickle cell disease. Persons with sickle cell trait usually do not have many symptoms of disease and have normal hospitalization rates and life expectancies. Sickle cell trait is present in some two million blacks in the United States (8% of the U.S. black population at birth). When two carriers of sickle cell trait mate, their offspring have a one in four chance of having Sickle cell disease. (In some parts of Africa, one in five persons is a carrier for sickle cell trait.)

What Are the Types of Sickle Cell Disease (Sickle Cell Anemia)?


Hemoglobin is the protein in RBCs that carries oxygen. It is made up of two alpha chains and two beta chains. These are made by the alpha and beta genes. The four main types of Sickle cell disease are caused by different mutations in these genes.

Sickle Cell Disease (Sickle Cell Anemia) Causes, Types, Symptoms, Diagnosis, Treatment, Prevention
Sickle Cell Disease (Sickle Cell Anemia)

Hemoglobin SS Disease


Hemoglobin SS disease is the most common type of sickle cell disease. It occurs when you inherit copies of the hemoglobin S gene from both parents. This forms hemoglobin known as Hb SS.

Hemoglobin SC Disease


Hemoglobin SC disease is the second most common type of sickle cell disease. It occurs when you inherit the Hb C gene from one parent and the Hb S gene from the other. Individuals with Hb SC have similar symptoms to individuals with Hb SS. However, the anemia is less severe.

Hemoglobin SB+ (Beta) Thalassemia


Hemoglobin SB+ (Beta) thalassemia affects beta globin gene production. The size of the red blood cell is reduced because less beta protein is made. If inherited with the Hb S gene, you will have Hemoglobin S Beta thalassemia.

Beta-Zero Thalassemia


Beta-Zero thalassemia is the second type of beta thalassemia. It has similar symptoms to Hb SS anemia. However, sometimes the symptoms of beta-zero thalassemia are more severe. It is associated with a poorer prognosis.

People who only inherit a mutated gene from only one parent are said to have sickle cell trait. They may have no symptoms or reduced symptoms.

What causes Sickle Cell Disease (Sickle Cell Anemia)?


The cause is inherited. It is a change in the genes which tell the body how to make an important protein called haemoglobin. To get Sickle Cell Disease, you need to have two altered haemoglobin genes, one from each parent. If you only have one of these genes, you will have sickle cell trait, which is very much milder.

The most common type of Sickle Cell Disease is where you have two sickle cell genes (sickle cell anaemia). The medical shorthand for this is haemoglobin SS or HbSS. Other types of sickle cell disease involve one sickle cell gene plus another abnormal haemoglobin gene of a different type. These include: haemoglobin SC; haemoglobin S/beta thalassaemia; haemoglobin S/Lepore; haemoglobin SO Arab.

The symptoms, diagnosis and treatment are similar for all the sickle cell conditions.

What Are the Symptoms of Sickle Cell Disease (Sickle Cell Anemia)?


Symptoms of Sickle cell disease usually show up at a young age. They may appear in babies as early as 4 months old.

Anemia


Anemia is a shortage of RBCs. Sickle cells are easily broken. This breaking apart of RBCs is called chronic hemolysis. RBCs generally live for about 120 days. Sickle cells live for a maximum of 10 to 20 days.

Symptoms of severe anaemia are:

  • Feeling tired, faint, short of breath, dizziness, nausea (feeling sick) or having fast breathing - worse with physical activity.
  • Babies and small children may be lethargic, not feeding much or generally unwell.
  • A pale skin colour (easiest to see in the lips, tongue, fingernails or eyelids).
  • With children, the spleen sometimes enlarges quickly and causes sudden severe anaemia. The enlarged spleen is in the abdomen (tummy) and can be felt. Parents may be shown how to feel their child's spleen. If the spleen enlarges quickly, it is a sign that urgent treatment is needed.

Acute chest syndrome


This occurs when there are blocked blood vessels in the lungs and can sometimes occur with a lung infection. 

The symptoms can include chest pain, fever and shortness of breath. Babies and young children may have more vague symptoms and look generally unwell, be lethargic, restless or have fast breathing. Acute chest syndrome is very serious and, if it is suspected, you should be treated urgently in hospital.

Acute chest syndrome can start a few days after a painful sickle crisis. It is most common in women who are pregnant or who have recently had a baby.

Infections


People with Sickle Cell Disease are more prone to severe infections, particularly from certain types of bacteria, which can cause pneumonia, meningitis, septicaemia or bone infections. (These include the pneumococcal, Haemophilus influenzae type b and meningococcal bacteria, and salmonella bacteria which can infect bones.) Symptoms of infection include fever, feeling generally ill, and pain in the affected part of the body.

Children with Sickle Cell Disease have a high risk of getting severe or life-threatening infections. It is important to see a doctor quickly if you suspect an infection or feel unwell.

Sickle Cell Disease (Sickle Cell Anemia) Causes, Types, Symptoms, Diagnosis, Treatment, Prevention
Sickle Cell Disease (Sickle Cell Anemia)

Hand-foot syndrome


Hand-Foot Syndrome occurs when sickle-shaped RBCs block blood vessels in the hands or feet. This causes the hands and feet to swell. It can also cause leg ulcers. Swollen hands and feet are often the first sign of Sickle cell disease in babies.

Splenic Sequestration


Splenic sequestration is a blockage of the splenic vessels by sickle cells. It causes acute, painful enlargement of the spleen.

Delayed Growth


Delayed growth often occurs in people with Sickle cell disease. Children are generally shorter but regain their height by adulthood. Sexual maturation may also be delayed. This happens because sickle cell RBCs can’t supply enough oxygen and nutrients.

How is Sickle Cell Disease (Sickle Cell Anemia) diagnosed?


Sickle cell disease is suggested when the abnormal sickle-shaped cells in the blood are identified under a microscope. Testing is typically performed on a smear of blood using a special low-oxygen preparation. This is referred to as a sickle prep. Other prep tests can also be used to detect the abnormal hemoglobin S, including solubility tests performed on tubes of blood solutions. The disease can be confirmed by specifically quantifying the types of hemoglobin present using a hemoglobin electrophoresis test.

Prenatal diagnosis (before birth) of Sickle cell disease is possible using amniocentesis or chorionic villus sampling. The sample obtained is then tested for DNA analysis of the fetal cells.

The hemoglobin electrophoresis test precisely identifies the hemoglobins in the blood by separating them. The separation of the different hemoglobins is possible because of the unique electrical charges they each have on their protein surfaces, causing them each to move characteristically in an electrical field as tested in the laboratory.

How Is Sickle Cell Disease (Sickle Cell Anemia) Treated?


A number of different treatments are available for Sickle cell disease.

Antibiotics like penicillin may be given from 2 months of age to 5 years. They help prevent pneumonia in sickle cell patients.

Pain medication is used to relieve the pain during a sickle crisis. You may need over-the-counter drugs or strong prescription pain medication like morphine.

Hydroxyurea (Droxia, Hydrea) helps to increase production of fetal hemoglobin. It may reduce the number of blood transfusions.

Immunizations can help prevent infections. Patients tend to have lower immunity. All the usual childhood vaccinations are advised.

Surgery may be used to treat persistent painful erections.

Bone marrow transplant has been used to treat Sickle cell disease. Children younger than 16 years of age who have severe complications and have a matching donor are the best candidates.

Blood transfusions can also treat Sickle cell disease. Packed red cells are removed from donated blood and given to patients. This improves transport of oxygen and nutrients.

Supplemental oxygen is given through a mask. It makes breathing easier and improves oxygen levels in the blood.

Prevention and Home Remedies for  Sickle Cell Disease (Sickle Cell Anemia)


Heating pads and relaxation may help you deal with pain.

Daily supplementation of folic acid and a healthy diet can help you make new RBCs. Fruits, vegetables, and whole-wheat grains are important.

Increased water drinking can reduce chances of a sickle cell crisis.

Avoiding extreme temperatures can also reduce the chance of a crisis. Exercising regularly and reducing stress may help as well.

Vitamin supplements: extra folic acid is usually recommended. This helps the body to make new red blood cells.

If you go to a country where there is malaria, then be extra careful to take malaria prevention medication and to prevent mosquito bites (people with Sickle Cell Disease can get very ill from malaria).

Avoid smoking (which is bad for blood vessels) and excess alcohol.

Support groups can help you deal with this condition. Learn all you can about the disease.

What are the possible complications of Sickle Cell Disease (Sickle Cell Anemia) ?


Possible complications of Sickle Cell Disease (Sickle Cell Anemia) in children


Growth, development and nutrition As with any long-term illness, a child with Sickle Cell Disease may grow more slowly than usual, or be undernourished if the illness affects their appetite.

Some children with Sickle: Cell Disease take longer than usual to gain control of their bladder at night, so may wet the bed. (The medical name for this is nocturnal enuresis.)

For teenagers, puberty may start about 2-3 years later than average.

The growth of bones can also be affected. For example, there may be changes in the hip or shoulder joints due to blocked blood vessels in that part of the bone.

Stroke or brain injury: This is a serious complication and affects about 1 in 10 children or teenagers with Sickle Cell Disease. If sickle cells block blood vessels in the brain, this may cause a stroke. There may be symptoms of stroke such as weakness of the face or limb, or speech difficulty. For some children, there may be no obvious symptoms. However, many tiny strokes may cause a subtle brain injury and make learning more difficult.

Spleen problems: The spleen is an organ located in the abdomen (tummy), in the top left-hand side. Its function is to help the immune system. Sickle cells can block blood vessels in the spleen. This can make the spleen swell up suddenly with blood - in effect, it is like losing blood into the spleen. This is one cause of sudden and severe anaemia, when your child becomes suddenly ill. The medical term is splenic sequestration. It needs urgent treatment with a blood transfusion. 

If this problem happens more than once, then one option is surgery to remove the spleen. However, by adulthood the problem normally resolves because the spleen becomes fibrosed (hard) and cannot swell.

Parvovirus infection: Parvovirus is a common infection in childhood. Normally it causes a mild illness with fever, flushed cheeks and a rash. With Sickle Cell Disease, the virus can upset the bone marrow, which then stops making blood for a while. This causes a severe anaemia and needs treating with blood transfusions until the bone marrow recovers.

Complications of blood transfusions: Transfusions can cause blood reactions. These are less likely if the blood is carefully matched to your blood type. Infections such as hepatitis B and C can be transmitted by transfusion. This is less likely in the UK and countries where donor blood is tested for infections. Hepatitis B vaccination is also recommended.

Repeated blood transfusions can overload the body tissues with iron. You may need tests to measure the iron level in the body. If iron levels get high, you may need treatment called chelation, which helps the body get rid of excess iron.

Possible complications of Sickle Cell Disease (Sickle Cell Anemia) in older teenagers and adults


Damage to various organs can develop gradually during teenage and adult years, due to repeated, small blockages of tiny blood vessels. The amount of complications varies from person to person. 

Lungs, heart and kidneys: Any of these organs may suffer some damage. Therefore, you will normally be offered regular checks on your heart, lungs and kidney function.

Eyes Regular eye checks are important. Sickle Cell Disease may cause changes to blood vessels in the back of the eye (retina); this is called retinopathy. For retinopathy, laser treatment is given to prevent further damage.

Also, sickle cells may cause sudden blockage of a blood vessel in the eye. If this happens, you will have a sudden reduction in your vision. This needs immediate treatment. So, always see a doctor quickly if your vision reduces suddenly in any way.

Unwanted erections: Some teenage boys and men with Sickle Cell Disease may get unwanted erections of the penis, which may be painful. The medical name for this is priapism. This can be quite brief, but if an erection does not subside within one hour then urgent treatment is needed. There are various treatments to relieve or prevent unwanted erections.

Gallstones: Stones in the gallbladder are more common in people with Sickle Cell Disease, and can cause bouts of pain in the upper right side of the abdomen (tummy). They may need treatment which is usually an operation to remove your gallbladder.

Leg ulcers: Leg ulcers can occur with Sickle Cell Disease, but are not common. Treatment is with dressings, and zinc supplements may help.

Complications of blood transfusions These are explained above for children, and also apply to adults.