Brittani Scott
Introduction
Sickle-cell disease is an illness that is multisystem, linked to episodes of progressive damage of organ and acute illness, and is among the most common dangerous monogenic disorders in the world (Weatherall, Hofman, Rodgers, Ruffin, & Hrynkow, 2005). The sickle-shape erythrocytes were initially described in the year 1910 by Herrick (Herrick, 1910) and understanding has slowly increased from that time. Together with his colleagues, Pauling (1949) keyed out electrophoretic abnormalities in sickle HbS and made up the word molecular disease in the year 1949. The genetics, as well as biophysics of hemoglobin behind the disease, have been widely studied and have aided in the apprehension of other molecular illnesses. Nevertheless, sickle-cell disease’s clinical management remains basic and, even though there is evidence to the use of hydroxycarbamide and blood transfusion in several circumstances, no drugs have been made that specifically aim at the pathophysiology of this illness.
Definition of Disease
Sickle-cell anemia, also referred to as drepanocytosis or sickle-cell disease, is a blood disorder that is hereditary, qualified by red blood cells, which take up an abnormal, stiff, sickle shape. Sickling reduces the flexibility of cells and leads to a risk of a number of complications. The sickling takes place due to a mutation in the gene of hemoglobin. Persons with a single copy of the defunct gene exhibit both abnormal and normal hemoglobin, which is an example of co-dominance. With sickle cell anemia, life expectancy is reduced. In the year 1994, in the United States, the mean life expectancy of people with this disease was approximated to be 42 and 48 years in males and females respectively (Platt, Brambilla, & Rosse, 1994), but currently, owing to improved management of the illness, patients are able to live into their 70s or longer (ANDALE, 2013).
Sickle-cell disease happens usually in persons whose ancestors were living in tropical as well as sub-tropical sub-Saharan areas where there is or was a common occurrence of malaria. Where there is a common occurrence of malaria, carrying a single gene for sickle-cell, also known as sickle cell trait, confers fitness. Specifically, human beings with a single of the two alleles of sickle-cell disease exhibit less severe signs when they acquire malaria (Wellems, K., & Fairhurst, 2009).
Sickle-cell anemia is a kind of sickle-cell disease where there is homozygosity for the mutation, which leads to HbS. Sickle-cell anemia is also termed as hemoglobin S, HbSS, SS disease, or substitutions of those names. In persons who are heterozygous, that is, possessing only a single sickle gene and a single normal adult hemoglobin gene, the condition is termed as sickle cell trait or HbAS. Other, less common sickle-cell disease forms are compound heterozygous states where the individual has just a single copy of the mutation, which leads to HbS and a single copy of another abnormal hemoglobin allele. They include sickle-haemoglobin C disease, abbreviated as HbSC, sickle beta-plus-thalassaemia, abbreviated as HbS/β+, and sickle beta-zero-thalassaemia, abbreviated as HbS/β0.
The word disease is used since the abnormality that is inherited leads to a pathological condition, which can result in death as well as severe complications. Not every inherited variant of hemoglobin is damaging, and this concept is referred to as genetic polymorphism (Wellems, Hayton, & Fairhurst, 2009).
Rates of Occurrence
The sickle cell anemia trait is frequently carried by persons from regions in the world who have a history of epidemics of malaria. This entails that the illness mostly affects persons from the Middle East, Africa, the Mediterranean region, as well as India. Carriers of the sickle cell anemia genetic trait have enhanced resistance to severe malaria of the falciparum type (Wellems, Hayton, & Fairhurst, 2009).
Nearly 2 % of the population of the world has the sickle cell trait, and approximately 3 % of all newborn babies are carriers. In Africa, more than 10 % of the population is carriers, whereas, in Europe, the occurrence is approximated to be 0.1 %. Over 225,000 babies, each year are born with sickle cell anemia. Out of these, 200,000 are from Africa and more than 20,000 in Asia, while, in Europe, the number is 200. There is no research of the occurrence in Sweden, but below 100 individuals have the disease, all of whom originate from nations where the disease is common (Embury, Mohandas, & Steinberg, 1994).
Risk Factors and/or Association with Other Disease
Sickle cell anemia is hereditary. Persons at risk for acquiring the gene for sickle cell are those from persons who are or were originally from parts of the Mediterranean and India as well as Africa. The gene for sickle cell also happens in persons from Central and South America, the Middle East, and the Caribbean. The high occurrence of the gene for sickle cell in these areas of the world is because of the ability of sickle cell to confer red blood cells’ resistance to the parasite of malaria. Persons who inherit only a single gene are known to possess the sickle trait. These people have protection against malaria and sickle cell disease and the diseases do not develop in them. Approximately 40% of persons in some parts of Africa and approximately 9% of African-Americans possess the trait.
Sickle cell disease develops in people who acquire the two copies of the HbS gene. They do not have protection from malaria, though. As a matter of fact, malaria is more severe in these persons. An approximated 1 out of 1,000 - 1,400 Hispanic Americans, as well as 1 out of 500 African-Americans, are born with sickle cell disease (Platt, et al., 1999).
Etiology of the Disease
Sickle cell anemia occurs as a result of a mutation in the gene that instructs the body to make hemoglobin, the red, iron-rich compound which offers blood its red color. Hemoglobin permits the red blood cells to transport oxygen from the lungs to every part of the body. In sickle cell anemia, the abnormal hemoglobin makes red blood cells to turn stiff, sticky as well as misshapen.
The gene for sickle cell is inherited from a generation to another in an inheritance pattern also referred to as autosomal recessive inheritance. This entails that both the father and the mother have to pass on the faulty form of the gene in order for their child to be affected.
Supposing just one parent passes the gene for sickle cell to the child, the child will possess the sickle cell trait. Having a single normal gene for hemoglobin and a single defective form of the gene, individuals with the sickle cell trait produce normal hemoglobin as well as sickle cell hemoglobin. Their blood might have a number of sickle cells, though they usually do not go through the symptoms. Nevertheless, they are carriers of the sickle cell disease, meaning that their children can inherit the defective gene from them.
With every pregnancy, two persons with sickle cell traits have a 25 % possibility of getting a child who is not affected with normal hemoglobin, a 50 % possibility of getting a child who is a carrier, as well as a 25 % possibility of getting a child having sickle cell anemia.
Natural History of the Disease
This clinical findings’ collection was not known until the explanation of sickle cells in the year 1910 by the Chicago cardiologist who was a professor of medicine by the name James Herrick. His intern Ernest Edward Irons discovered curious elongated as well as sickle-shaped cells. These cells were found in the blood of a 20-year-old student from Grenada by the name of Walter Clement Noel, following admission to the Chicago Presbyterian Hospital in December 1904 for treatment of anemia (Herrick, 1910).
Noel was admitted again a number of times for the three years that followed for muscular rheumatism as well as bilious attacks. Noel finished his studies and went back to the capital of Grenada to exercise dentistry. He passed away from pneumonia in 1916 and was entombed in the north of Grenada in the Catholic cemetery at Sauteurs (Savitt & Goldberg, 1989). The published account of Herrick included illustrations, though the first available slide demonstrating sickle cells is one of an autopsy in 1918 from a soldier who had sickle trait, initially reexamined only 92 years afterwards (Maryn, 2011).
The disease was termed sickle-cell anemia in 1922 by Verne Mason, then a medical resident at Johns Hopkins Hospital (Mason, 1922). Nevertheless, a number of factors of the disease had been distinguished earlier. A paper published in 1846 in the Southern Journal of Medical Pharmacology depicted the spleen absence in a runaway slave’s autopsy. The literature of the African medical Journal described this condition in the 1870s, when it was recognized locally as ogbanjes due to the very high rate of infant mortality contributed by this condition. A chronicle of the condition trailed reports back to 1670 in a Ghanaian family (Desai & Hiren, 2004).
Linus Pauling together with his colleagues was the first to show that sickle-cell disease happens as a consequence of a hemoglobin molecule abnormality, in the year 1949. This was the first instance a hereditary condition was related to a mutation of a particular protein, a milepost in the chronicle of molecular biology, and it was issued in their paper.
Approaches to Detection or Diagnosis (Screening)
Sickle cell anemia is suspected when the abnormal sickle-shaped cells in the blood are keyed out under a microscope. Examination is generally carried out on a blood smear by use of a special low-oxygen preparation. This is known as sickle prep. Other prep examinations can as well be utilized to identify the abnormal hemoglobin S, which include solubility tests carried out on tubes of solutions of blood. The disease may be affirmed by distinctively quantifying the hemoglobin types present by use of a hemoglobin electrophoresis test.
Approaches to diagnoses of the disease involve laboratory investigations and imaging studies. Laboratory analyses include blood analysis, hemolysis studies, peripheral smear, end organ damage, hemoglobin studies, and bacterial cultures, among others. Imaging studies include plain X-rays, transcranial Doppler ultrasound or magnetic resonance imaging for assessment of risk for or diagnosis of stroke, and bone scan for differentiation of pain crises bone pain from that of osteomyelitis (Clarke & Higgins, 2000).
Approaches to prevention/community control
The strategies of treatment for sickle cell anemia may be categorized into four different groups, namely preventive measures, fetal hemoglobin production stimulation, symptom alleviation, as well as gene replacement therapy.
Preventive measures
Strategies ought to be taken to preclude sickle cells from blocking blood vessels, leading to depletion of oxygen as well as damage of potential organ. It is also essential that prophylactic strategies are taken to permit the person to develop as well as live life as ordinarily as possible.
Children below the five years of age are especially susceptible to infections ought to, based on the signs, be cured with antibiotics. In a number of cases, prophylactic antibiotics ought to be administered. Administering vaccines against pneumococcal illnesses as well as hepatitis are also encouraged.
Hydroxyurea treatment with the objective of raising fetalfetallobin ought to be taken into consideration for persons who have gone through a number of sickle crises, with severe chronic pain, or those at a high jeopardy of stroke. The other treatment alternative is regular transfusions of blood so as to decrease the part of sickle cells within the bloodstream. There are, nevertheless, several complications linked to transfusions of blood, for instance overload of iron, which needs medical treatment. Transplantation of blood stem cells may as well be taken into considered in a number of cases, a procedure frequently termed as bone marrow transplantation (Walters, Eckman, Scott, Mentzer, & Sullivan, 1996).
It is essential that people suffering from sickle cell anemia as well as those who are close to them are informed well concerning the disorder and the way to manage and treat it. Information ought to be provided on recurrent junctures and ought to be adapted to age. Every parent ought to learn how to evaluate their children with respect to difficulties in breathing, pallor as well as spleen size. It is also significant that the two parents together with the affected person learn to utilize medication of pain relief properly.
Persons suffering from sickle cell anemia ought to take care not to get cold or dehydrated, and ought to thus drink lot of fluids, put on adequately warm clothing in low temperatures, as well as not swimming in cold water. Activities at high heights, beyond 3000 meters, where the level of oxygen is low, also ought to be avoided. Air travel in cabins that are pressurized presents no problems.
Social and psychological support are essential, since sickle cell anemia is mentally and physically trying for the persons who are affected, who have to experience repeated crises of pain leading to long absences from school. Under these situations, low self-pride as well as negative feelings are ordinary. Having a person to share ideas with is among the ways of relieving the problems, and setting up contact with a counselor or a psychologist can be helpful. It is essential that the family of the patient is in regular close interaction with a care provider with good information about the disorder. The family also ought to have access to a professional’s network with knowledge concerning the disease.
Treatment of symptoms
Acute signs as well as complications contributed by the disease, which include vaso-occlusive crises, acute spleen sequestration, acute chest syndrome and aplastic crises, require being relieved and cured. The cure comprises of offering enough hydration, pain relief, antibiotics and at times oxygen therapy or transfusions of blood. As the pain is frequently severe, it is essential to plan for usual effectual control of pain. The patient ought to have proper information concerning self-dispensed treatment at home, although he/she should also know how to distinguish conditions that may need hospital care.
Stimulation of fetal hemoglobin (HbF) production
A high HbF proportion in the blood reduces the jeopardy that sickling will take place. A number of chemical agents raise the level of HbF, but at present hydroxyurea is the drug selected for sickle cell anemia treatment. Hydroxyurea, a cytotoxic substance, is utilized in the treatment of malignancies, and prolonged usage raises the danger of leukemia as well as fetal damage in gestation. It is for this reason that hydroxyurea is just dispensed in severe instances of sickle cell anemia. There are no set up guideline for deciding who ought to be cured with this drug. Nevertheless, the positive impacts can be viewed in both minors and adults, and as hydroxyurea lowers the danger of vaso-occlusive crises and repeating stroke, its utilization has a likelihood of increasing.
Replacement of the defective gene
If a minor suffering from sickle cell anemia has a brother or sister with the indistinguishable type of tissue, a transplant of blood stem cell can be carried out. Every blood cell is produced by bone marrow’s stem cells, which is a sponge like tissue in the bone’s cavities. In blood stem cells transplantation, the blood stem cells of the suffering child can be substituted with new ones obtained from the healthy donor. Types of tissue are transmitted from both parents, and every child has a 25% possibility of getting a similar type of tissue as a sibling. If the transplant is carried out successfully, the child is cured fully. Nevertheless, the process is highly demanding and requires key risks, which include a raised death rate. Moreover, the new stem cells recipient is frequently affected by permanent damage of organs which can result in infertility. On account of the dangers involved, there are no universal recommendations that ascertain who ought to be transplanted, and each case calls for individual assessment.
Sickle-cell anemia is preventable. Parents who are at risk of getting affected children can be keyed out through cheap and dependable tests of blood where sampling of chorionic villus from two months of pregnancy can be carried out for ante partum diagnosis. Embracing of such strategies goes together with apposite health education. Nevertheless, ante partum diagnosis can elicit ethical questions that are different from one society to another. Experience has evidently demonstrated that giving genetic counseling together with the provision of ante partum diagnosis can result in a large-scale decrease in births of children who are affected. The danger of having children who are affected can be discovered prior to marriage or pregnancy. However, doing this calls for a carrier-screening program. There is widespread experience with these kinds of programs in low- and high-income nations. For instance, in the instance of thalassaemia preclusion, single people in the Maldives and Montreal are provided with screening, antenuptial screening is national strategy in Cyprus as well as Iran, and pre-generative screening is stressed in Italy and Greece. These strategies ought to be exercised in conformance with the three central rules of medical genetics. These include the individual’s or the couple’s autonomy, their right to sufficient and whole information and the highest confidentiality standards.
Research in a number of nations like Burkina Faso, Benin, Togo and Nigeria has afforded agents of therapy that are effective in precluding or cutting down the severity and occurrence of crises. There is enough proof that neonatal sickle-cell disease screening, when related to well-timed diagnostic testing, complete care and parental education, noticeably cuts down mortality and morbidity in infancy and early childhood. However, simple, cheap and cost-efficient procedures like the usage of penicillin to preclude infections are not available to the majority of patients (WHO, 2012).
Conclusion
Sickle-cell disease management at varying levels of the system of health-care ought to stress programs that employ simple, low-cost technology and are easy to get for a large part of the community. Such programs are opted instead of a system that are parallel that may be very expensive as well as unsustainable. The program ought to be developed at the basic care level with suitable technical support as well as support of patient referral from higher care levels. Health personnel training in preclusion, diagnosis, and case management ought to assure that the system of health-care has the ability to offer the basic demands of these services. Family as well as community-based care ought to be an inherent part of the national programs.
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