Sickle Cell Disease

1. What is Sickle Cell Disease (SCD?
2. How does Sickle Cell Disease affect the body?
3. How common is Sickle Cell Disease?
4. What are the clinical features?
5. Major complications.
6. Living with Sickle Cell Disease.
7. Prevention
8. Treatment options for SCD.
9. Ten Commandments for patients with SCD.
10. Resources for Sickle Cell Disease patients.

What is Sickle Cell Disease?
Sickle Cell Disease (SCD) is the most prominent member of a group of inherited disorders of the oxygen carrying cells of blood. The specific abnormality is well known and involves the substitution of one protein building block called an amino acid for another amino acid at a key point in one of the chains of the major protein of red blood cells. This protein is called hemoglobin. The change in the structure of hemoglobin is thought to have been precipitated by efforts to gain a measure of protection from the scourge of malaria in areas where it is endemic. Thus sickle cell disease and its closely related variants are found in areas where malaria has a high prevalence. The disease is inherited in classic Mendelian fashion, which means that the likelihood of passing the disease on to offspring's can be statistically estimated based on the status of parents as either carriers of the gene responsible or as actual sufferers of the disease.

How does Sickle Cell Disease affect the body?
As mentioned earlier in this article, the fundamental problem in SCD is abnormal hemoglobin. This abnormal hemoglobin is very sensitive to conditions of low oxygen within the body. Under these conditions, the abnormal hemoglobin loses its solubility in blood and forms thick strands that are called polymers. These polymers tend to hold the red blood cells in rigid banana or half moon shapes, hence the term "sickle cell". These rigid cells travel very poorly through the circulation and are often trapped in small vessels where they obstruct the flow of blood and blood borne nutrients. The circulatory obstruction produces the characteristic pain, and when severe or complete it may lead to tissue and organ death due to inadequate oxygen and nutrients. The body also recognizes the sickle cells as abnormal and they are trapped and destroyed by the spleen and the liver. Large-scale destruction of deformed cells results in the other major feature of this disease; anemia (inadequate red blood cells). The death of tissue can affect virtually every organ of the body, but organs that require a lot of blood flow or oxygen to function properly are particularly vulnerable. For this reason, the kidneys, lungs, brain, spleen, liver and bone are disproportionately affected.

How common is Sickle Cell Disease?
SCD affects millions of people around the world, particularly in Africa, the Mediterranean, and Asia. One in eight black Americans harbors the trait, while approximately one in 400 has the disease. The prevalence in children is higher than in adults because a significant number of children afflicted with the disease do not survive to adult-hood.

What are the clinical features?
The dominant clinical feature is severe pain affecting the limbs, chest and abdomen. These patients are frequently hospitalized for intolerable pain, and they often require powerful painkillers to keep them comfortable. Severe anemia, as previously alluded to, causes weakness, reduced exercise tolerance, and a pale appearance. A pigment called bilirubin, which is formed from the breakdown of blood cells, causes a yellow discoloration of the white portion of the eyeballs. More serious problems include strokes, severe difficulty breathing, kidney failure and an increased susceptibility to infections in general, and particularly to a bacteria called pneumococcus. SCD patients have a frail appearance, which may be accentuated by a very prominent forehead. Other conditions that occur more frequently in SCD patients include gallstones and leg ulcers.

Major complications
Major complications include heart and kidney failure, stroke, and a very dangerous form of lung failure called "sickle chest syndrome". Occasionally, the bone marrow shuts down and the patient is unable to make any new red blood cells at a time when large numbers of cells are being destroyed. This serious condition is known as aplastic anemia and can result in death if not treated promptly with blood transfusions and other measures.

Living with Sickle Cell Disease
A few decades ago few patients with Sickle Cell Disease survived long enough to become adults. With improvements in the understanding of the disease process, therapeutic strategies have significantly improved the outlook for all but the most severely afflicted patients. It is however an incurable disease at this time, and patients who survive past infancy must learn to live with the disease and to adhere to recommendations for mitigating the most damaging consequences of the disease, based on almost three decades of accumulated scientific data. Some of the more important does and don'ts will be outlined below in the section on the "Ten Commandments for sickle cell patients".

Prevention
Prevention efforts are limited to genetic counseling since SCD is an inherited congenital illness. Fortunately, its simple mendelian inheritance, and the availability of a simple, reliable, and inexpensive test means that most individuals at risk due to ethnic background or other reasons, can be easily screened and counselled prior to marriage and having children. Pre-natal diagnosis is also available by a process called amniocentesis, whereby a sample is obtained from the baby while it is still in the uterus, and if the baby is found to have the condition, the pregnancy can be terminated within the first three months. There have been recently published reports of a number of strategies to prevent frequent attacks of pain and severe anemia but they are still essentially experimental, and long-term side effects are unknown. Finally, some of the serious infections that patients are vulnerable to can be prevented by vaccination. All sickle cell patients should receive the vaccine for against the bacteria called pneumococcus.

Treatment options for SCD
Given the present state of knowledge, Sickle Cell Disease remains an incurable disease. Active research is being conducted into potentially curative, innovative forms of therapy such as gene therapy, and bone marrow transplantation. Until such a cure emerges, therapeutic strategy is focused on providing maximum patient comfort while trying to minimize the consequences of sickling on end organ function. Analgesics are the main stay of treatment designed to maximize comfort. Most physicians who care for sickle cell patients use analgesics liberally during acute painful crises without worrying about addiction potential, although some patients who require large doses of potentially addictive drugs do eventually show some evidence of addiction. Blood transfusions are given when necessary to maintain acceptable levels of hemoglobin and to reduce the frequency of painful crises. However, over-transfusion is a real hazard as it may lead to excessive accumulation of iron in the body. This leads to heart and liver failure and can also precipitate diabetes mellitus. Frequent transfusion also increases the risk of AIDS and other blood borne diseases. Folic acid and other vitamin supplements are frequently prescribed but, in the absence of other reasons for vitamin deficiency, their utility is not conclusively proven. Recently, a cancer-fighting chemical called Hydroxyurea has been tested on sickle cell patients and appears to reduce the frequency and severity of crises. Long-term side effects are unknown however, and the treatment must be considered experimental at this time.

BHO Ten Commandments for patients with SCD

1. Thou shall not smoke!!
2. Thou shall not smoke!!
3. Thou shall not smoke!!
4. Find a good hematologist (blood diseases specialist) and seek periodic check ups.
5. Thou shall avoid dehydration by ensuring access to adequate fluids at all times.
6. Ask your doctor about recommended vaccinations and follow his advice.
7. Eat a healthy balanced diet and try to adopt a generally healthy life-style.
8. When you feel unwell, seek medical attention as early as possible.
9. Read about your disease and be as well informed about it as possible.
10. Obtain Genetic testing and counseling prior to marriage and childbirth.

Resources for Sickle Cell Disease patients.

1. American Sickle Cell Anemia Association
    http://www.ascaa.org

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