Sickle cell anaemia
SICKLE CELL ANAEMIA
SICKLE CELL ANAEMIA DEFINITION
Sickle cell anemia is an inherited form of anemia — a condition in which there aren’t enough healthy red blood cells to carry adequate oxygen throughout your body.
Normally, your red blood cells are flexible and round, moving easily through your blood vessels. In sickle cell anemia, the red blood cells become rigid and sticky and are shaped like sickles or crescent moons. These irregularly shaped cells can get stuck in small blood vessels, which can slow or block blood flow and oxygen to parts of the body.
There’s no cure for most people with sickle cell anemia. However, treatments can relieve pain and help prevent further problems associated with sickle cell anemia.
SICKLE CELL ANAEMIA CAUSES
Abnormal hemoglobin, called hemoglobin S, causes sickle cell disease (SCD).
The problem in hemoglobin S is caused by a small defect in the gene that directs the production of the beta globin part of hemoglobin. This small defect in the beta globin gene causes a problem in the beta globin part of hemoglobin, changing the way that hemoglobin works.
SICKLE CELL ANAEMIA PATHOPHYSIOLOGY
HbS arises from a mutation substituting thymine for adenine in the sixth codon of the beta-chain gene, GAG to GTG. This causes coding of valine instead of glutamate in position 6 of the Hb beta chain. The resulting Hb has the physical properties of forming polymers under deoxy conditions. It also exhibits changes in solubility and molecular stability. These properties are responsible for the profound clinical expressions of the sickling syndromes.
Under deoxy conditions, HbS undergoes marked decrease in solubility, increased viscosity, and polymer formation at concentrations exceeding 30 g/dL. It forms a gel-like substance containing Hb crystals called tactoids. The gel-like form of Hb is in equilibrium with its liquid-soluble form. A number of factors influence this equilibrium, including oxygen tension, concentration of Hb S, and the presence of other hemoglobins.
Oxygen tension is a factor in that polymer formation occurs only in the deoxy state. If oxygen is present, the liquid state prevails. Concentration of Hb S is a factor in that gelation of HbS occurs at concentrations greater than 20.8 g/dL (the normal cellular Hb concentration is 30 g/dL). The presence of other hemoglobins is a factor in that normal adult hemoglobin (HbA) and fetal hemoglobin (HbF) have an inhibitory effect on gelation.
These and other Hb interactions affect the severity of clinical syndromes. HbSS produces a more severe disease than sickle cell HbC (HbSC), HbSD, HbSO Arab, and Hb with one normal and one sickle allele (HbSA).
When red blood cells (RBCs) containing homozygous HbS are exposed to deoxy conditions, the sickling process begins. A slow and gradual polymer formation ensues. Electron microscopy reveals a parallel array of filaments. Repeated and prolonged sickling involves the membrane; the RBC assumes the characteristic sickled shape.
SICKLE CELL ANAEMIA SYMPTOMS
Signs and symptoms of sickle cell anemia often don’t appear until an infant is at least 4 months old and may include:
- Anemia. Sickle cells are fragile. They break apart easily and die, leaving you without a good supply of red blood cells. Red blood cells usually live for about 120 days before they die and need to be replaced. But sickle cells die after an average of less than 20 days. This results in a lasting shortage of red blood cells (anemia). Without enough red blood cells in circulation, your body can’t get the oxygen it needs to feel energized. That’s why anemia causes fatigue.
- Episodes of pain. Periodic episodes of pain, called crises, are a major symptom of sickle cell anemia. Pain develops when sickle-shaped red blood cells block blood flow through tiny blood vessels to your chest, abdomen and joints. Pain can also occur in your bones. The pain may vary in intensity and can last for a few hours to a few weeks. Some people experience only a few episodes of pain. Others experience a dozen or more crises a year. If a crisis is severe enough, you may need to be hospitalized.
- Hand-foot syndrome. Swollen hands and feet may be the first signs of sickle cell anemia in babies. The swelling is caused by sickle-shaped red blood cells blocking blood flow out of their hands and feet.
- Frequent infections. Sickle cells can damage your spleen, an organ that fights infection. This may make you more vulnerable to infections. Doctors commonly give infants and children with sickle cell anemia vaccinations and antibiotics to prevent potentially life-threatening infections, such as pneumonia.
- Delayed growth. Red blood cells provide your body with the oxygen and nutrients you need for growth. A shortage of healthy red blood cells can slow growth in infants and children and delay puberty in teenagers.
- Vision problems. Some people with sickle cell anemia experience vision problems. Tiny blood vessels that supply your eyes may become plugged with sickle cells. This can damage the retina — the portion of the eye that processes visual images.
SICKLE CELL ANAEMIA DIAGNOSIS
People who do not know whether they make sickle hemoglobin (hemoglobin S) or another abnormalhemoglobin (such as C, β thalassemia, E) can find out by having their blood tested. This way, they can learn whether they carry a gene (i.e., have the trait) for an abnormal hemoglobin that they could pass on to a child.
When each parent has this information, he or she can be better informed about the chances of having a child with some type of sickle cell disease (SCD), such as hemoglobin SS, SC, Sβ thalassemia, or others.
When a child has SCD, it is very important to diagnose it early to better prevent complications.
Every state in the United States, the District of Columbia, and the U.S. territories require that every baby is tested for SCD as part of a newborn screening program.
In newborn screening programs, blood from a heel prick is collected in “spots” on a special paper. The hemoglobin from this blood is then analyzed in special labs.
Newborn screening results are sent to the doctor who ordered the test and to the child’s primary doctor.
If a baby is found to have SCD, health providers from a special follow-up newborn screening group contact the family directly to make sure that the parents know the results. The child is always retested to be sure that the diagnosis is correct.
Newborn screening programs also find out whether the baby has an abnormal hemoglobintrait. If so, parents are informed, and counseling is offered.
Remember that when a child has sickle cell trait or SCD, a future sibling, or the child’s own future child, may be at risk. These possibilities should be discussed with the primary care doctor, a blood specialist called a hematologist, and/or a genetics counselor.
Doctors can also diagnose SCD before a baby is born. This is done using a sample of amniotic fluid, the liquid in the sac surrounding a growing embryo, or tissue taken from the placenta,the organ that attaches the umbilical cord to the mother’s womb.
Testing before birth can be done as early as 8–10 weeks into the pregnancy. This testing looks for the sickle hemoglobin gene rather than the abnormal hemoglobin.
SICKLE CELL ANAEMIA TREATMENT
Bone marrow transplant offers the only potential cure for sickle cell anemia. But finding a donor is difficult and the procedure has serious risks associated with it, including death.
As a result, treatment for sickle cell anemia is usually aimed at avoiding crises, relieving symptoms and preventing complications. If you have sickle cell anemia, you’ll need to make regular visits to your doctor to check your red blood cell count and monitor your health. Treatments may include medications to reduce pain and prevent complications, blood transfusions and supplemental oxygen, as well as a bone marrow transplant.
Medications used to treat sickle cell anemia include:
- Antibiotics. Children with sickle cell anemia may begin taking the antibiotic penicillin when they’re about 2 months of age and continue taking it until they’re at least 5 years old. Doing so helps prevent infections, such as pneumonia, which can be life-threatening to an infant or child with sickle cell anemia. Antibiotics may also help adults with sickle cell anemia fight certain infections.
- Pain-relieving medications. To relieve pain during a sickle crisis, your doctor may advise over-the-counter pain relievers and application of heat to the affected area. You may also need stronger prescription pain medication.
- Hydroxyurea (Droxia, Hydrea). When taken daily, hydroxyurea reduces the frequency of painful crises and may reduce the need for blood transfusions. Hydroxyurea seems to work by stimulating production of fetalhemoglobin — a type of hemoglobin found in newborns that helps prevent the formation of sickle cells. Hydroxyurea increases your risk of infections, and there is some concern that long-term use of this drug may cause tumors or leukemia in certain people. However, this hasn’t yet been seen in studies of the drug.
Hydroxyurea was initially used just for adults with severe sickle cell anemia. Studies on children have shown that the drug may prevent some of the serious complications associated with sickle cell anemia. But the long-term effects of the drug on children are still unknown. Your doctor can help you determine if this drug may be beneficial for you or your child.
Assessing stroke risk
Using a special ultrasound machine (transcranial), doctors can learn which children have a higher risk of stroke. This test can be used on children as young as 2 years, and those who are found to have a high risk of stroke are then treated with regular blood transfusions.
Vaccinations to prevent infections
Childhood vaccinations are important for preventing disease in all children. But, these vaccinations are even more important for children with sickle cell anemia, because infections can be severe in children with sickle cell anemia. Your doctor will make sure your child receives all of the recommended childhood vaccinations. Vaccinations, such as the pneumococcal vaccine and the annual flu shot, are also important for adults with sickle cell anemia.
In a red blood cell transfusion, red blood cells are removed from a supply of donated blood. These donated cells are then given intravenously to a person with sickle cell anemia.
Blood transfusions increase the number of normal red blood cells in circulation, helping to relieve anemia. In children with sickle cell anemia at high risk of stroke, regular blood transfusions can decrease their risk of stroke.
Blood transfusions carry some risk. Blood contains iron. Regular blood transfusions cause an excess amount of iron to build up in your body. Because excess iron can damage your heart, liver and other organs, people who undergo regular transfusions may need treatment to reduce iron levels. Deferasirox (Exjade) is an oral medication that can reduce excess iron levels.
Breathing supplemental oxygen through a breathing mask adds oxygen to your blood and helps you breathe easier. It may be helpful if you have acute chest syndrome or a sickle cell crisis.
Stem cell transplant
A stem cell transplant, also called a bone marrow transplant, involves replacing bone marrow affected by sickle cell anemia with healthy bone marrow from a donor. Because of the risks associated with a stem cell transplant, the procedure is recommended only for people who have significant symptoms and problems from sickle cell anemia.
If a donor is found, the diseased bone marrow in the person with sickle cell anemia is first depleted with radiation or chemotherapy. Healthy stem cells from the donor are filtered from the blood. The healthy stem cells are injected intravenously into the bloodstream of the person with sickle cell anemia, where they migrate to the bone marrow cavities and begin generating new blood cells. The procedure requires a lengthy hospital stay. After the transplant, you’ll receive drugs to help prevent rejection of the donated stem cells.
A stem cell transplant carries risks. There’s a chance that your body may reject the transplant, leading to life-threatening complications. In addition, not everyone is a candidate for transplantation or can find a suitable donor.
Doctors treat most complications of sickle cell anemia as they occur. Treatment may include antibiotics, vitamins, blood transfusions, pain-relieving medicines, other medications and possibly surgery, such as to correct vision problems or to remove a damaged spleen.
Scientists are studying new treatments for sickle cell anemia, including:
- Gene therapy. Because sickle cell anemia is caused by a defective gene, researchers are exploring whether inserting a normal gene into the bone marrow of people with sickle cell anemia will result in the production of normal hemoglobin. Scientists are also exploring the possibility of turning off the defective gene while reactivating another gene responsible for the production of fetal hemoglobin — a type of hemoglobin found in newborns that prevents sickle cells from forming. Potential treatments using gene therapy are still a long way off, however. No human trials using genes specifically for sickle cell have yet been done.
- Nitric oxide. People with sickle cell anemia have low levels of nitric oxide in their blood. Nitric oxide is a gas that helps keep blood vessels open and reduces the stickiness of red blood cells. Treatment with nitric oxide may prevent sickle cells from clumping together. Studies on nitric oxide have had mixed results so far.
- Drugs to boost fetal hemoglobin production. Researchers are studying various drugs to devise a way to boost the production of fetal hemoglobin. This is a type of hemoglobin that stops sickle cells from forming.
- Statins. These medications, which are normally used to lower cholesterol, may also help reduce inflammation. In sickle cell anemia, statins may help blood flow better through blood vessels.