Sickle Cell Anemia
Definition and description succinct outline of sickle cell anemia is as follows.
Sickle cell anemia is an inherited blood disorder characterized primarily by chronic anemia and periodic episodes of pain. The underlying problem involves hemoglobin, a component of red blood cells….In sickle cell anemia, the hemoglobin is defective. After hemoglobin molecules give up their oxygen, some may cluster together and form long, rod-like structures. These structures cause red blood cells to become stiff and assume a sickle shape. (Genetic Disease Profile: Sickle Cell Anemia)
Sickle cell anemia is in essence a condition in which there is insufficient healthy blood cells to convey oxygen to the body. A second cardinal aspect is that it is an inherited and largely genetically determined illness. (Sickle cell anemia)
Sickle cell disease can result in a number of disorders including “…chronic anemia, jaundice, severe pain, poor resistance to infection and sometimes an early death.” (Pines 40) This disease has genetic origans and parameters and “…affects some 50,000 Americans, mostly blacks.” (Pines 40)
In more detail, sickle cell disease can be described as originating from an anomaly in cell structure and”… has been traced to a single gene and the resulting misplacement of just one amino acid out of 300 in the hemoglobin molecules of the victims’ red blood cells.” (Pines 40) In this disease the cells become distorted and deviate for their normal healthy shape. This results in structure that is similar to a crescent or a sickle – hence the name. The distortion of shape in the cell results in a number of internal abnormalities in the cell structure. “The abnormal cells may stick together, obstructing the small blood vessels and causing damage as well as pain, or be removed too rapidly by the spleen, causing anemia.” (Pines 40)
Figure 1. An illustration of the difference between a normal blood cell and a sickled cell.
Sufferers of sickle cell anemia have abnormal hemoglobin known as hemoglobin S; while normal hemoglobin is termed hemoglobin A.
Sickle cell anemia originates from a genetic anomaly which “makes the hemoglobin molecules stick together in long, rigid rods after they release oxygen. These rods cause the red blood cells to become hard and sickle-shaped, unable to squeeze through tiny blood vessels.” (New Hope for People with Sickle Cell Anemia) These cells can then obstruct blood flow resulting in blockages that deprives the body of vital oxygen.
This sequence of events has been described as being similar to a heart attack throughout the body. “In sickle cell anemia, the blood flow can be interrupted to any of the major organs, causing severe pain and organ damage at the site of the blood flow blockage.” (New Hope for People with Sickle Cell Anemia) Attacks like this can damage numerous vital organs such as the lungs, kidneys, liver, bones, as well as other organs and tissues. Furthermore, it can result in various related health problems such as blindness, leg ulcers as well as strokes, due to the interruption of the flow of blood to the brain.
As a result of the fact that the bodies defenses realize that these cells are abnormal, it consequently destroys these cells at a rate that exceeds their replacement and this results in anemia. This makes the sufferer more susceptible to tiredness and infection. (New Hope for People with Sickle Cell Anemia) “Normal red blood cells live about 120 days in the bloodstream, but sickled red cells die after about 10 to 20 days. Because they cannot be replaced fast enough, the blood is chronically short of red blood cells, a condition called anemia.” (Genetic Disease Profile: Sickle Cell Anemia)
Inheritance and genetics
Research has shown that the genetic origins of this defective hemoglobin gene lie mainly in Africa, as well as in, the Mediterranean, the Middle East and India. (Sickle cell anemia) The mutation of this gene has also been linked to a defense mechanism against malaria in these parts of the world. “…some people in those regions had a genetic mutation that caused some of their red blood cells to change shape — a condition now known as sickle cell trait. The sickle cells actually interfered with the growth of the parasite that causes malaria. So people with sickle cell trait often survived malaria outbreaks.” (Sickle cell anemia)
An important aspect of Sickle cell disease is that as many as two million Americans are carriers of this cellular defect and can transmit the disease through marriage to their partners who also have the same abnormal cellular structure. In terms of its genetic structure “…Sickle cell anemia is an autosomal recessive genetic disorder caused by a defect in the HBB gene, which codes for hemoglobin.” (New Hope for People with Sickle Cell Anemia)
In order for sickle cell anemia to manifest itself the presence of two defective genes (SS) are needed. In other words, if two parents are the carriers of one sickle hemoglobin gene (S) as well as a single normal cell (A) then each chills born for these parents will have a “…25% chance of inheriting two defective genes and having sickle cell anemia; a 25% chance of inheriting two normal genes and not having the disease; and a 50% chance of being an unaffected carrier like the parents.” (New Hope for People with Sickle Cell Anemia)
Individuals who have only one copy of the mutation are said to have sickle cell trait. These people are usually healthy but can transmit the disease to their children.
This aspect is clarified by the fact that, “Sickle Cell trait (AS) is an inherited condition in which both hemoglobin A and S. are produced in the red blood cells, always more A than S. Sickle cell trait is not a type of sickle cell disease. People with sickle cell trait are generally healthy.” (What is Sickle Cell Disease?)
In more technical parlance the gene that is known to be the cause of sickle cell anemia is termed HbS. “Sickle cell anemia is actually a group of diseases collectively termed hemoglobinopathies in which normal adult hemoglobin (HbA) is partly or completely replaced by abnormal sickle hemoglobin (HbS). Other correct terms are SS and homozygous sickle cell disease.” (Sickle Cell)
Sickle cell anemia affects approximately 50,000 Americans and its incidence is mainly distributed among those of African heritage. (Sickle cell anemia)
In the United States about one in every four hundred African-American infants is born with the disease as a result of inheriting the genetic mutation from both parents. (New Hope for People with Sickle Cell Anemia) It is also estimated that those individuals who have the sickle cell trait number one in twelve of the African-American population.
However, this disease is not limited to people of African heritage and can occur in non-African-Americans.
People whose ancestors came from parts of the world where malaria was prevalent are potentially carriers of the sickle gene…In addition to people of African descent; people whose ancestors came from the Mediterranean basin-Greece, Italy, Sardinia-may also carry the gene. The sickle gene is also found in parts of India and the Arabian peninsula.
New Hope for People with Sickle Cell Anemia)
The estimated mortality rate for Sickle Cell Anemia is approximately 500 people in America annually. However the rate of incidence of the disease in the U.S.A. is 72,000, with an estimated 2 million carriers of the disease. The rate of death compared to prevalence is 0.70%, which also indicates the relative success of modern methods of treatment – an aspect that will be referred to in the last section of this paper. (Prognosis of Sickle Cell Anemia)
There is no clear-cut single set of clinical symptoms for this disease. The symptoms can range from relatively mild reactions in some patients to severe and life-threatening signs in others. However the common denominators in all patients who suffer for this disease are that their symptoms can be related to the problem of restricted blood flow.
The following are some of the most common symptomatic signs. A condition known as hand-foot syndrome is common. This is “When small blood vessels in hands or feet are blocked, pain and swelling can result, along with fever. This may be the first symptom of sickle cell anemia in infants.” (Genetic Disease Profile: Sickle Cell Anemia) Another common symptom is fatigue, which is often accompanied by shortness of breath. These are obvious signs of anemia due to the shortage of red blood cells.
Patients can also experience unpredictable pain in their joints or body organs. “A patient may experience pain wherever sickled blood cells block oxygen flow to tissues. The frequency and amount of pain vary. Some patients have painful episodes (also called crises) less than once a year, and some have as many as 15 or more episodes in a year.” (Genetic Disease Profile: Sickle Cell Anemia)
Sufferers of this disease can also experience eye problems. This is due to the fact that a lack of circulating blood can case the retina of the eye to deteriorate. Another symptom that is often found is a yellowing of skin and eyes; this is a sign of jaundice due to the breakdown of red blood cells. Another sign is that children may show delayed growth and development. (Genetic Disease Profile: Sickle Cell Anemia)
One of the aspects that problematizes this disease are the complications that can arise as a result of the lowering of body defenses and the increased vulnerability to illness. This can be ascribed to spleen damage. The disease “….prevents the spleen from destroying bacteria in the blood. Infants and young children, especially, are susceptible to bacterial infections that can kill them in as little as 9 hours from onset of fever.” (Genetic Disease Profile: Sickle Cell Anemia)
Stroke is anther serious possible consequence of this disease. This can result from defective cells damaging the walls of red blood vessels.
6. Brief historical overview.
While the HbS gene is usually found in Africa, yet there is very little evidence and reporting of this gene in African medical literature until the 1870s.
One reason given for this is that many of the symptoms of sickle cell anemia are similar to other diseases found on the continent. (Sickle Cell) Therefore most of the reports and published documentation about the disease are related to studies of patients in the United States.
One of the very first published medical papers on this disease was, “Case of Absence of the Spleen” in the Southern Journal of Medical Pharmacology, published in 1846 in America. (Sickle Cell)
However one of the first modern formal reports on the disease was published in Chicago 1910. This report was to establish the name of the disease. “In the western literature, the first description of sickle cell disease was by a Chicago physician, James B. Herrick, who noted in 1910 that a patient of his from the West Indies had an anemia characterized by unusual red cells that were “sickle shaped.” (A Brief History of Sickle Cell Disease)
The following are some of the most significant events related to the historical study and research of sickle cell anemia.
Taliafero and Huck first recognized that the sickling phenomenon was an inherited condition in 1923. (Ingram 38)
In 1927, Hahn and Gillespie showed that sickling of the red cells was related to low oxygen. (A Brief History of Sickle Cell Disease)
In 1948, using a new technique known as protein electrophoresis, Linus Pauling and Harvey Itano showed that “…the hemoglobin from patients with sickle cell disease is different than that of normals. This made sickle cell disease the first disorder in which an abnormality in a protein was known to be at fault.” (A Brief History of Sickle Cell Disease)
In 1949, Neel and Beet, independently, put forward the now accepted view that individuals with the severe sickle cell anemia were homozygous for an abnormal gene and that sickle-cell trait carriers were heterozygous, having one normal and one abnormal gene.” (Ingram 38)
In 1956, sickle cell disease became the first genetic disorder whose molecular basis was known. This was achieved by Vernon Ingram and J.A. Hunt who “…sequenced sickle hemoglobin and showed that a glutamic acid at position 6 was replaced by a valine in sickle cell disease. Using the known information about amino acids and the codons that coded for them, they was able to predict the mutation in sickle cell disease. “(A Brief History of Sickle Cell Disease)
The first reported cure of sickle cell disease took place in 1984, when bone marrow transplantation in a child with sickle cell disease produced the first reported cure of the disease. “The transplantation was done to treat acute leukemia. The child’s sickle cell disease was cured as a side-event. The procedure nonetheless set the precedence for later transplantation efforts directed specifically at sickle cell disease.” (A Brief History of Sickle Cell Disease)
Another important breakthrough occurred in 1986 when a study found that “…young children with sickle cell anemia who took penicillin twice a day by mouth had much lower rates of S. pneumoniae infection than a similar group of children who received a placebo.” (A Brief History of Sickle Cell Disease)
In 1987, a panel of experts recommended that “…all infants born in the United States be screened for sickle cell anemia so that children with the disease could be identified early and offered treatment with penicillin.” (New Hope for People with Sickle Cell Anemia)
In 1995 a drug known as Hydroxyurea became the first and only drug that was successful in preventing various complications that could result from sickle cell disease. (A Brief History of Sickle Cell Disease)
7. Prognosis and treatment.
At present there is, except for bone marrow transplant, no known cure for sickle cell disease. However ” Transplants are complicated procedures and aren’t an option for everyone.” (Sickle Cell Disease) Transplants often have extreme risk factors are also made problematic by donor matching and rejection issues. This is indicated in the following explanation of the dangers of this process. “First you give drugs to kill off the patient’s marrow, then you do the transplant to replace the marrow. But the powerful drugs given to kill the patient’s bone marrow can be dangerous for someone who has had a stroke or is at risk for stroke.” (New Hope for People with Sickle Cell Anemia)
However, while there is as yet no definitive cure for this disease many studies point out that “…life expectancy for individuals with sickle cell anemia has improved.” (New Hope for People with Sickle Cell Anemia) This is largely a result of early identification techniques and neonatal screening. Other factors such as penicillin therapy and early intervention have gone a long way to the alleviation of the more severe symptoms of the disease. “Improving treatment has raised lifespans into the 40’s and rising. ” (Prognosis of Sickle Cell Anemia)
As mentioned above, a recent breakthrough is the use of the drug Hydroxyurea. This has been found to be beneficial in treating the complications as well as the levels of pain in the sufferers of sickle cell anemia. However the full and long-term effects of this drug are not yet fully known and doctors only prescribe it under certain conditions. There are also a number of questions about its impact on the body and health that still need to be answered.” Many questions about hydroxyurea in the treatment of sickle cell anemia remain unanswered…Doctors do not know what the most effective and least toxic dose of the drug is or whether taking it for many years presents health risks.” (New Hope for People with Sickle Cell Anemia)
Gen therapy is an avenue that is being explored in the fight against this disease. The National Heart, Lung and Blood Institute (NHLBI) recently funded three centers to develop gene therapy for sickle cell anemia. As one medical expert states; “If you could replace the abnormal genes, you could cure the disease. However, there are significant technical problems involved in making gene therapy work.” (New Hope for People with Sickle Cell Anemia)
Prehospital and EMS care and management of the disease are also factors that needs consideration. It is recommended that prehospital care is feasible when the severity of the disease is not extreme and “…self-treatment at home with bed rest, oral analgesia, and hydration is possible.” (Anemia, Sickle Cell)
However if the situation worsens and the patient has to be transported by EMS, “…they should receive supplemental oxygen and intravenous hydration en route to the hospital,” (Anemia, Sickle Cell) Prehospital management of sickle cell crisis should also include management of pain and involves the “… tailoring analgesics and dosages to the level of pain experienced by the patient, ” as well as the “…administration of analgesics, including narcotics and NSAIDs, intracellular hydration with hypotonic fluids, bed rest, and antibiotics to treat underlying infection and other precipitants.” (Paris et al. 2005)
The treatment and management of this disease has shown considerable advancement, which is evidenced by the decrease in the mortality rate. “In the past, individuals with sickle cell anemia often died in childhood. A 1973 study estimated that half of those with the disease died by the age of 14.” (New Hope for People with Sickle Cell Anemia) This situation no longer applies and there is new hope for sufferers of this disease in the use of modern drugs, the increased awareness of the disease and the promise of gene therapy. There has also been research into the way that life habits can reduce the effects and complications of this disease. “…increasing knowledge about their specific effects on human development has led to various forms of environmental treatment: medications, diet, or a change in life habits. ” (Pines 40)
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What is Sickle Cell Disease? May 30, 2006. http://www.sicklecelldisease.org/about_scd