Sickle cell Anemia

Sickle cell anemia is an inherited blood disorder. The disease occurs due to a defect in the genes that produce hemoglobin inside the red blood cells.

In sickle cell disease, there is a defect in the structure of hemoglobin, which is a protein present in your red blood cells. Your red blood cells have the shape of a disc normally. This defect causes your red blood cells to have a sickle shape, and hence the name sickle cell disease.

It also leads to the loss of flexibility of the red blood cells, which is essential for the blood to move through your blood vessels. The lack of flexibility causes the red blood cells to rupture very easily, leading to a decrease in their numbers in the blood. The result is that you have sickle cell anemia.

Sickle cell anemia affects both men and women. It is more common in people of African descent.

If you have sickle cell anemia, the most common symptom you will have is severe fatigue and tiredness. It is due to a decrease in oxygen levels in the blood. You will be prone to various infections.

 ‘Pain crisis’, where you may have severe pain, which lasts for hours, in parts of the body like the chest, abdomen, joints, etc. is another major symptom. Some major complications are stroke, severe lung problems, damage to major organs like spleen, kidney, liver, eyes, etc.

Medications will help you to control the symptoms to a degree. Blood transfusions will help to increase the number of red blood cells if the anemia is severe. 

Stem cell transplant is the only curative treatment for sickle cell anemia. It involves the transplantation of healthy donor stem cells into the bone marrow of the patient.

What causes sickle cell disease?

You have sickle cell anemia if the genes that control the production of hemoglobin is defective. You get these defective genes from your parents. Genes carry the information to control the functions of your body, and they work in pairs. You receive a copy from your mother and one from your father to make the pair.

For you to have sickle cell anemia, both the copies of the genes that control the production of hemoglobin should be defective. If you have only a single gene, either from the mother or father that is defective, you have a sickle cell trait. In this, you will not have any symptoms of the disease as the healthy gene of the pair helps to produce normal hemoglobin. But you can pass on the defective gene to your son or daughter by being a carrier.

Persons with sickle cell anemia will have hemoglobin S, which is different in structure and shape from normal hemoglobin. It causes the red blood cells to have a sickle- shape than the usual disc shape. Red blood cells need to be very flexible to move smoothly through small blood vessels. But the sickle-shaped red blood cells find it difficult to move through these blood vessels. These also tend to rupture more easily, leading to anemia.  

Risk factors of sickle cell disease

Sickle cell anemia is an inherited blood disorder where there is a defect in the pair of genes that control hemoglobin production. You are at risk if both your parents have the disease or act as carriers of the defective gene. You have a one in four chance to have the disease in this situation. 

Sickle cell anemia is more common in people of African descent. People of Mediterranean and Asian descent are also among the high-risk group.

Symptoms of sickle cell disease

The main symptoms are

• Fatigue and tiredness- If you have sickle cell anemia, you will feel tired all the time. It is because of a decrease in the levels of oxygen in the blood. Your RBCs will have a shorter life than usual as they rupture easily. Your hemoglobin levels will fall as low as 6 to 7 g/ dl.
• Pain crisis or Vaso-occlusive crisis - It occurs due to the ‘occlusion’ or obstruction of small blood vessels due to the clumping of red blood cells. It causes severe pain in the chest, abdomen, limbs, etc. The episodes will last for a few hours to a few days. Dehydration, breathing problems, changes in body temperature, etc. are the most common triggers. 
• Hand- Foot syndrome or dactylitis- It usually affects infants and children below the age of five. Children will have severe swelling of the extremities like the hand and foot.
• Recurrent infections- It occurs due to damage to the spleen, that is responsible for the production of lymphocytes necessary to fight infections.
• Bone pain- It occurs due to the formation of infarcts in the bone.
• Joint pain- Due to the necrosis of the joints due to loss of blood supply. 
• Chest pain- Due to infarcts in the ribs, lungs, etc.
• Abdominal pain- It may occur due to the congestion of the spleen or liver. Poor growth and maturity- Children with the disease will have poor growth. Sexual maturity may also be less.

Almost all other symptoms occur due to the abnormal sickle shape of the red blood cells. It prevents them from moving smoothly through the blood vessels resulting in blocks to the normal flow of blood. It also causes various complications that affect almost all parts of the body.

Sickle cell anemia complications

All the complications occur due to obstruction of blood flow to various parts of the body. Loss of blood supply to certain areas will result in the formation of infarcts where the cells in the area die due to a lack of oxygen.

• Acute chest syndrome- You will have severe chest pain, fever, cough, difficulty in breathing, increased breath rate, etc. It occurs due to the formation of infarcts in the ribs, lungs, etc. Fat embolism due to bone marrow infarction is another cause.
• Splenic sequestration- It occurs due to the trapping of a large number of sickled blood cells inside the spleen. The result is an enlargement of the spleen as wells as a loss of its function. Complete damage may occur if there is any delay in treating the condition.
• Aplastic crisis- It happens when your bone marrow fails to produce enough red blood cells for a few days. In those with sickle cell anemia, the life cycle of red blood cells is around twenty days, much below the standard fifty to sixty days. So if the bone marrow does not produce enough red blood cells for a week or two, the effects can be severe. 
• Stroke- It occurs due to obstruction of blood flow in the arteries in the brain. Brain hemorrhages may also occur due to the rupture of aneurysms that form due to injury to blood vessels.
• Cognitive problems- Children with sickle cell anemia may have infarcts in the brain. Infarcts are areas where the brain cells die due to a loss of blood supply. It affects skills like memory, learning ability, problem-solving, etc.
• Lung problems- Pulmonary hypertension, where the blood pressure in the lungs rises above normal, is common. It causes breathing difficulties as well as the formation of fluid in the lobes of the lungs
• Liver problems- Bile stones are common in those with sickle cell anemia. It leads to infections of the liver.
• Kidney problems- The most common one is the inability of the kidneys to concentrate urine. It thus leads to a loss of lots of water through urine, causing severe dehydration.
• Eye problems- Infarcts in the blood vessels of the retina may cause vision problems. A progressive loss of vision may also occur. Ptosis may also occur in a few due to infarctions in the muscles that control eyelid movements. 
• Heart problems-  Some may develop dilation of both the ventricles and left atrium and also of the coronary arteries
• Leg ulcers- It usually occurs around the ankles. Minor injuries can cause wounds that fail to heal properly due to a decrease in blood supply. Infections compound the problem, leading to non-healing ulcers.
• Priapism- It is a long, painful, and unwanted erection of the penis. In this condition, the blood that flows into the penis fails to return. It is due to the trapping of the sickled cells in the blood vessels.
• Bone problems- Apart from bone and joint pain, there are some other complications as well. Common ones are osteomyelitis, septic arthritis, vertebral problems, osteoporosis, osteopenia, etc. The lower jaw or mandible may be larger than normal.

Diagnosis of sickle cell disease

If you have sickle cell anemia, a blood test will help to diagnose it. Observing your blood smear under a microscope will reveal the sickle shape of the red blood cells.

Electrophoresis helps to precisely identify the type of hemoglobin.

Treatment of sickle cell disease

Sickle cell anemia treatment includes medicines, blood transfusions, and stem cell or bone marrow transplant.

Medicines

Medical treatment aims to control the symptoms and prevent complications. The common medications are

Antibiotics – Daily doses of penicillin can help to prevent infections.

Hydroxyurea- It helps to prevent the sickled cells from sticking together and thereby obstructing the blood flow. Is effective in treating or preventing ‘pain crises’

Folic acid supplements- To improve the production of red blood cells.

Painkillers- To control pain. 

Blood transfusions

If you have very severe hemolytic anemia, you will need blood transfusions. It helps to improve the levels of hemoglobin significantly. Transfusions are usually necessary for complications like splenic sequestration, aplastic crisis, severe acute chest syndrome, and severe priapism.

Bone marrow transplant for sickle cell disease

A bone marrow transplant is the only treatment to cure sickle cell anemia. More than 85% of people report an event-free life after treatment. Some severe symptoms or complications do not respond to medicines, and transfusions also may need a stem cell transplant.

You will have a stem cell/bone marrow transplant if you have severe complications like

• Stroke
• Severe acute chest syndrome
• Severe and recurrent pain crises occurring more than twice or thrice a year
• A progressive loss of vision
• Severe kidney problems

During the treatment, you will receive healthy stem cells that can develop into normal red blood cells from a donor. Before the transplant, you will have chemotherapy and radiation to destroy your diseased stem cells.

You will have the transfusion into your bloodstream through a large blood vessel in the chest. Once in the bloodstream, the healthy stem cells move into and occupy the empty bone marrow space. After some time, the stem cells start producing normal and healthy red blood cells.

You will be in the hospital for about two weeks for the transplant. Recovery will take about two to three months. 

Prognosis of sickle cell disease

With proper treatment, persons with sickle cell anemia can have an event-free life. Complications like stroke, lung problems, etc. can be life-threatening. Stem cell transplant improves the survival rate significantly