An Effective Cure for Sickle Cell Disease - Term Paper Example

Sickle Cell Disease Sickle cell disease is an inherited genetic disorder that leads to the polymerization of deoxygenated hemoglobin S, andcauses the red blood cells to take up a sickle cell shape. This change of shape results in blocking of the blood vessels by the sickle red blood cells and inadequate blood supply to the tissues and organs. The consequence of this vaso-occlusion results in a variety of clinical manifestations of the disease that include crisis events associated with multi-system inadequacies, resulting in the high rate of morbidity and mortality associated with sickle cell disease. Diagnosing sickle cell disease involves the use of the more expensive gene analysis or hemoglobin electrophoresis, isoelectric focusing, and high-performance liquid chromatography. There is no curative treatment for sickle cell disease, except for bone marrow stem cell transplantation, which is extremely limited in use. The most potent current therapy available is the anticancer drug hydroxyurea, with its ability to raise the levels of fetal hemoglobin and thereby reduce the frequency and intensity of the life threatening crisis events of sickle cell disease. Managing pain is the key to the satisfactory management of sickle cell disease. However, the lack of adequate knowledge of pain management techniques quite often leads to unsatisfactory outcomes from the patient’s perspective. Research continues in the hope of finding an effective cure for sickle cell disease 1. Introduction Gulbis et al, 2005 p.309, describes sickle cell disease as “a genetic disorder involving hemoglobin designated as hemoglobin S, an autosomic recessive hereditary disease. This inherited disease causes the normally round and flexible red blood cells to become stiff and shaped like a sickle, from whence it derives its name. The stiff sickle shaped blood cells no longer flow through blood vessels easily, hampering blood supply to the tissues. The resultant inadequate blood supply is responsible for the characteristic features of pain and respiratory difficulties experienced by patients suffering from sickle cell disease, and it is also responsible for organ damage in sickle cell disease. These sickle shaped blood cells die much faster than normal red blood cells, which lead to anemia. In essence the genetic alteration that occurs in sickle cell disease is the single base-pair change in the gene that is responsible for encoding a part of the hemoglobin protein. Such an alteration results in distorted hemoglobin protein production, which does not function adequately (Nestor et al, 2004). 2. Incidence The incidence of sickle cell disease is predominantly in the regions of the world, where malaria is endemic, with particular emphasis on the continent of Africa. Some of the African people have developed partial resistance to malaria genetically. It is believed that blood oriented diseases like sickle cell disease have survived through the history of human beings as a result of this genetically derived partial resistance to malaria (Nestor et al, 2004). Millions of people around the world are affected by sickle cell disease. The prevalence of sickle cell disease essentially is among those individuals with an ancestral linking to sub-Saharan Africa, South America, the Caribbean, Central America, Saudi Arabia, India, Turkey, Greece, and Italy. This makes many ethnic groupings in the United States of America prone to sickle cell disease. However, it is the African American ethnic group that is most prone to sickle cell disease. More than 70,000 individuals in the United States are affected by sickle cell disease, with sickle cell disease being witnessed in one in every five hundred African American births. In the United States of America about two million individuals carry the sickle cell trait, with one in every twelve African Americans carrying the sickle cell trait. Sickle cell disease is major health concern in the United States of America, as it is responsible for over seventy-five thousand hospitalizations, which cost the nation about $ 475 million every year (CDC, 2008). 3. Pathophysiology The essential risk factor for inheriting sickle cell disease is genetics, for both the parents need to carry the sickle cell gene for their offspring to inherit sickle cell disease. Sickle cell disease is however not a single form disease. The most frequently occurring form of the disease is the one inherited from both parents carrying the single cell gene and this form of the disease is the most severe and is termed SS. A milder form of the disease occurs when there is inheritance of one single cell gene from one parent and one gene from the other parent for another abnormal type of hemoglobin called C. This form of the disease is termed SC. There is a third form called S-beta-thalassemia, wherein one sickle cell gene is inherited from one parent and one gene is inherited for beta-thalassemia. When only one gene is acquired from any parent the individual carries the sickle cell trait, but does not demonstrate any signs or symptoms of the disease (Creary, Williamson & Kulkarni, 2007). The genetically transmitted autosomal recessive disorder sickle disease occurs through the amino acid substitution of valine for glutamic acid at the sixth position of the hemoglobin molecule in red blood cells. The consequence of this substitution is the instability of the hemoglobin molecule within the red blood cells in the deoxygenated state, at which time HbS polymerizes and makes the red blood cells undergo a change of shape from the normal biconcave shape to the irregular sickle shaped red blood cells. This unusual shape of the red blood cells and their being prone to adhere to the walls of the blood vessels results in occlusion of the blood vessels, and by that prevents the normal flow of blood, reducing the oxygen availability to the tissues and organs, which can lead to the crisis condition. In addition the red blood cells that have been forced into changing shape are also very prone to hemolysis, which can lead to chronic anemia in individuals with sickle cell disease (Edwards et al, 2005). Clinical Characteristics The commonly occurring clinical manifestations of the disease are essentially multi-system and stem from either anemia like jaundice, fatigue and shortness of breath or from the hindrance to blood flow from the sickle-shaped red blood cells like pain and damage to organs from inadequate oxygen supply. The onset of the initial signs and symptoms occur within five to six months of birth and persist right through the life of the individual. The course of the disease is not the same for all individuals. It can remain asymptomatic, particularly in the case of newborns or can lead to intermittent crisis events that require hospitalization of the individual for managing and treating the crisis episode. Infections can give rise to sudden drop in hemoglobin, which is termed as aplastic crisis. However, crisis episodes of pain are characteristic of sickle cell disease and are the consequence of vaso-occlusion that results from the blocking of the blood vessels by the misshapen red blood cells. These crisis events common to sickle cell disease can be brought on by dehydration, exposure to cold, infection and the environment in which there is low oxygen content, like high altitudes. The nature of the crisis events can be acute or chronic or both. These crisis events recur and cannot be predicted. A serious issue with sickle cell disease is the ischemic organ damage that can occur from the vaso-occlusion. The severe consequences of ischemic organ damage include stroke, pulmonary infarction or acute chest syndrome, priapism or prolonged painful erection, splenic infarcts or changes in the functioning of the spleen that result in enhanced susceptibility to infections, and damage to the kidneys and liver. Such organ damage causes quite frequently other conditions linked to the disease, like delayed growth, delay in puberty, and reduced lung function (Creary, Williamson & Kulkarni, 2007). Diagnostic Methods Sickle cell disease is the result of a disorder in the genetic disorder of an individual. Analysis of the DNA of an individual is the most accurate means to the diagnosis of sickle cell disease irrespective of the analysis being done pre natal or at any age. Advances in our understanding of the typical DNA sequence of the human gene from the Human Genome Project have assisted in the accuracy of DNA analysis in the diagnosis of sickle cell disease (Nestor et al, 2004). The drawback with DNA analysis is that it is still an expensive route to the diagnosis of sickle cell disease, which brings into play other diagnostic methods for sickle cell disease. The diagnostic methods for newborns and at other ages include hemoglobin electrophoresis, isoelectric focusing, and high-performance liquid chromatography. These methods used after birth separate the separate hemoglobin species based on their amino acid composition. These three diagnostic methods offer an alternative to DNA analysis with comparable accuracy. The choice of the diagnostic method is normally based on the availability of the diagnostic method locally and the affordability of the individual for the diagnostic method. In recent times the examination of peripheral blood smear as a diagnostic method has emerged. However the accuracy of this method in the diagnosis of sickle cell disease is yet to be ascertained (Wethers, 2000). Solubility testing methods is another diagnostic aid available for the diagnosis of sickle cell disease, but it suffers from inaccuracies making it an inappropriate diagnostic method. Solubility testing methods do identify sickle hemoglobin, but they do not identify hemoglobin C and the other genetic variants. The presence of a predominant proportion of fetal hemoglobin in a newborn makes solubility testing methods poor diagnostic aids in the diagnosis of sickle cell disease in newborns. Another drawback with solubility testing methods is its inability to detect sickle hemoglobin in individuals with severe anemia. (Wethers, 2000). Advanced Practice Management According to Creary, Williamson & Kulkarni 2007, the only treatment method that offers a cure for sickle cell anemia is peripheral blood or bone marrow stem cell transplantation taken from matched siblings. This procedure aids in the formation of normal red blood cells and through that offers a cure for sickle cell disease, but it suffers from drawbacks that has restricted its use and offers hope only for a select group of individuals. The drawbacks include mortality and morbidity risks involved in the procedure itself and the variable clinical severity of the patients. Though there is reduced life expectancy in sickle cell disease, advances in the understanding of the disease coupled with the advances in medical science and technology have contributed to increased life expectancy in individuals with sickle cell disease, well beyond the age of eighteen, which makes the goal of advanced practice management in sickle cell disease as prevention of its complications that give rise to crisis episodes (Creary, Williamson & Kulkarni 2007). Traditionally the non-specific management techniques to prevent crisis events in sickle cell disease include penicillin prophylaxis, pain medications, blood transfusions and vaccines. A new therapy that has emerged is the use of hydroxyurea. Hydroxyurea is a drug that has been used in the treatment of slow growing cancer. Observations of increased fetal in the use of hydroxyurea in cancer patients have created a new role for it in the treatment of sickle cell disease. Fetal hemoglobin is not involved in the polymerization of hemoglobin and through that lowers the sickling of the red blood cells. Fetal hemoglobin levels in the blood start to reduce around the age of six months. The use of hydroxyurea therapy increases the levels of fetal hemoglobin in adolescents and adults reducing endothelial adhesion of sickle cells and vaso-occlusive problems and increases cell hydration. Hydroxyurea therapy does offer a cure for sickle cell disease, but has shown the capability to half the hospitalizations in sickle cell disease as a result of vaso-occlusive complications and acute chest syndromes, thereby reducing the intensity and frequency of crisis events associated with sickle cell disease (Creary, Williamson & Kulkarni 2007). Management of pain in sickle cell disease is the most challenging aspect of the disease. Severe pain episodes can start occurring from the age of six onwards, when the fetal hemoglobin proportion begins to drop and pain episodes continue to occur all through the life of the individual. Pain management in sickle cell disease is deficient, because of misconceptions on the cause of the pain and the fear of addiction in the use of opioid analgesics (Claster & Vichinsky, 2003). Frequently the overdosing with opioids stems from the lack of adequate knowledge in pain management among the healthcare staff attending on the patient (Duffin, 2008). Given that severe pain crisis events are the most frequent cause for hospitalization, it is essential that health care staff associated with management of these patients have a proper understanding of not just managing the immediate pain crisis event, but also the coping with chronic pain condition that is a constant companion of sickle cell disease outside of the hospital environment. Evidence emerging from studies suggest that adult patients with sickle cell disease expect this support from the health care associated with the management of their disease condition and are currently dissatisfied with support received (Booker et al, 2006). Research Implications The pathological changes associated with sickle cell disease is due to the polymerization of deoxygenated hemoglobin S. Current research into finding an effective treatment for the disease targets the increase in the levels of fetal hemoglobin, which due to its high affinity for oxygen is not involved in polymerization, as a means to prevent polymerization and reverse the pathological processes. Research is progressing into meeting this objective of increased fetal hemoglobin levels either through pharmacological means or through the use of gee therapy and genetic engineering (Coleman & Inusa, 2007). The pharmaceutical approach to increase the levels of fetal hemoglobin has resulted in evaluation of butyrate and decitabine. Drugs to reduce the impact of sickle cell disease are also being studied. Clotrimazole, magnesium, and ICA-17043 quintiles are being evaluated to ascertain their efficacy in preventing dehydration of the sickle red blood cells. Nitric oxide is a strong vasodilator with anti-sickling properties, which has led to evaluation of nitric oxide as a potential drug in the treatment of sickle cell disease. Other avenues being explored by research include the search for anti-adhesion agents and anti-oxidative agents for the treatment of sickle cell disease (Claster & Vichinsky, 2003). Summary Sickle cell disease is an inherited genetic disorder that gives rise to misshapen red blood cells, due to the polymerization of deoxygenated hemoglobin S. The disease is closely associated with the regions in which there is a prevalence of malaria. This has resulted in a high incidence of sickle cell disease among the African American population in the United States of America. The consequence of the misshapen red blood cells is that the blood vessels get blocked leading to inadequate oxygen supply to the tissues and organs, leading to complications from the ischemic condition. This vaso-occlusion associated with sickle cell disease leads to varied forms of clinical manifestations of the disease, which are multi-system oriented and give rise to crisis events. DNA analysis is the most accurate method for the diagnosis of sickle cell disease, but it is still expensive. Other diagnostic methods that can be used include hemoglobin electrophoresis, isoelectric focusing, and high-performance liquid chromatography. Bone marrow stem cell transplantation is the only treatment method that offers some hope of cure in sickle cell disease, but its application is extremely limited. In the current management options for sickle cell disease, the use of hydroxyurea is the best option; as it is found to increase the levels of fetal hemoglobin and through tat reduce the frequency and severity of the crisis events. Managing pain is the most challenging aspect with sickle cell disease. Yet, pain management is frequently inadequate in the management of sickle cell disease, essentially stemming from the lack of knowledge of adequate pain management techniques. Research still continues to find treatments that hold better hope for a cure of sickle cell disease. Literary References Booker, J.M., Blethyn, L.K., Wright, J. C. & Greenfield, M.S. (2006). Pain management in sickle cell disease. Chronic Illness, 2, 39-50. Center for Disease Control and Prevention (CDC). (2008). Sickle Cell Disease. Retrieved November 19, 2008, from, Department of Health and Human Services Web Site: http://www.cdc.gov/ncbddd/sicklecell/hcp_data.htm Claster, S. & Vichinsky, P.E. (2003). Managing Sickle Cell Disease. British Medical Journal, 327(7424), 1151-1156. Coleman, E. & Inusa, B. (2007). Sickle Cell Anemia: Targeting the Role of Fetal Hemoglobin in Therapy. Clinical Pediatrics, 46(5), 386-390. Creary, M., Williamson, D. & Kulkarni, R. (2007). Sickle Cell Disease: Current Activities, Public Health Implications and Future Directions. Journal of Women’s Health, 16(5), 575-582. Duffin, C. (2008). :Sickle cell disease: evidence suggests that the emergency care of patients with sickle cell disease or thalassaemia can be improved. Emergency Nurse, 16(4), 10-13. Edwards, C.L., Scales, M.T., Loughlin, C., Bennett, C.G., Harris-Petersen, S., De Castro, L.M., Whitworth, E., Abrams, M., Feliu, M., Johnson, S. Wood, M., Harrison, O. & Killough, A. (2005). A brief review of the pathophysiology, associated pain, and psychosocial issues in sickle cell disease. International Journal of Behavioral Medicine, 12(3), 171-179. Gulbis, B., Ferster, A., Kentos, A. Munungi, N.D., Cotton, F., Ronge, E. Dresse, M.F, Bradstreet, C., Cochaux, P. & Vertongen, F. (2005). Sickle cell disease: exotic disease or a Belgian public health problem? Revue medicale de Bruxelles, 26(4), 309-313. 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