Sickle Cell Anemia

Sickle Cell Anemia
For this assignment (Conclusion of the Case Report), include previous Parts 1, 2, and 3 of
the Case Report in one document, combined with additional genetics information learned
from the assigned readings from all course topics. This final Case Report document should
include the following:

  1. Describe the disease, its prevalence, its incidence and general knowledge of the disease.
  2. Discuss the laboratory testing that can be done.
  3. Describe if chromosomal analysis is/was indicated, and detail the chromosomal change
    that caused the disease if it is a chromosomal disorder.
  4. Describe the disorder in terms of its origin as either a single gene inheritance, or as a
    complex inheritance and considerations for practice and patient education.
  5. Describe the gene mutation of the disease, as well as whether it is acquired or inherited,
    and how the mutation occurs.
  6. Examine how genetics can influence policy issues.
  7. Discuss any nutritional influences for this disease.
  8. Process of nutritional assessment and counseling as it relates to health, prevention,
    screening, diagnostics, prognostics, selection of treatment, and monitoring of treatment
    Continue your paper with 1,000 words which include the following:
  9. Discuss any ethical considerations for this disease.
  10. Compare how genetics can improve care and health outcomes while reducing cost to
    usual practices.
  11. Discuss the changes in approaches to care when new evidence warrants evaluation of
    other options for improving outcomes or decreasing adverse events.
  12. Create a plan for how you might educate colleagues and/or patients on this genetic


Sickle Cell Anemia

Sickle cell anemia is a condition characterized by abnormally shaped red blood cells, leading to
the reduced amount of hemoglobin below normal limits for age and sex. According to Parachuri
et al, .( 2018), sickle cell disease is a condition characterized by abnormally shaped red blood
cells, thus reducing the amount of normally shaped and hence functional red blood cells below
the normal limits for the specific age and gender (Paruchuri, Kulkarni, Himes, & Kuklina, 2018).
Sickle cell anemia is a genetically acquired condition of the blood and the following essay will
discuss the various aspects of sickle cell anemia (Yawn, Buchanan, Afenyi-Annan, Ballas,
Hassell, James, & Tanabe, 2014).
Description, Prevalence, Incidence and General Knowledge
Sickle cell disease is among the fatal disorders that are mostly inherited. Approximately
100,000 people in America have the disorder. It is most prevalent among people of the African
origin. About one person among 12 African Americans has the disease and one among 100
Hispanic Americans have the sickle cell trait meaning that they are carriers.
Sickle cell disease and its variants are very prevalent among the malaria-endemic areas
especially in Africa and the Mediterranean (Yawn et al., 2014). Sickle cell disease mortality rates
are highest among teenage age. The following study analysis of sickle cell disease, its
prevalence, incidence and laboratory testing have been done. Moreover, guidelines and reasons
behind FDA regulations for a new policy, economics of health care and the role and family
involvement in the healthcare decision are elaborated.


Genetic Analysis and Origin
Sickle cell disease is an autosomal disorder, which causes red (Chou et al., 2013) cell to
acquire a curved shape resembling a sickle, thus their name. This disorder results from genetic
inheritance of defective hemoglobin genes from parents to children, where if both parents have
recessive genes for sickle cell, 25 % of the children will have the disorder (Yawn et al., 2014).
The abnormally shaped hemoglobin diminishes the ability of red blood cells to transport oxygen
efficiently. Sickle cell disease is characterized by presence the hemoglobin S, as a result of gene
mutation. This hemoglobin is very stable in the presence of hemolytic agents and remains intact
unlike the customarily shaped one, which lyses efficiently. The most common signs and
symptoms are acute and chronic aches at the feet, hands, back; universal anemia; delay sexual
maturity; growth retardation and respiratory problems (Yawn et al., 2014) among others. Sickle
cell disease symptoms are frequently experienced during a strenuous exercise (Yawn et al.,
2014). The sickle-shaped cells have a high likelihood of clogging the blood vessels and deterring
blood circulation.
The prevalence and incidences of sickle cell disease are most common in sub-Saharan
Africa and the Mediterranean region; also, in the Spanish speakers. Approximately 75, 000
hospital admissions have been diagnosed with sickle cell disease in the United States of America
(USA), with mortality rates highest among the children aged below three years. The annual
expenditure in the treatment of sickle cell disease is approximately 30 thousand dollars annually
in the USA.


Laboratory Testing
Some laboratory tests have been designed to test for sickle cell disease. These include
both blood tests and radiographic examinations. Among the blood-based tests are hemoglobin
solubility test, hemoglobin electrophoresis, pulmonary and liver function tests. The imaging tests
are chest X-ray, Magnetic resonance imaging (MRI) Computed tomography, abdominal
ultrasonography, Nuclear medicine scanning and the Transcranial Doppler ultrasonography
(Yawn et al., 2014). The hemoglobin solubility test is carried out under the principle that the
abnormally curved red blood cells are resistant to lyses and oxygenation. Therefore, in their
deoxygenated states, they will remain intact after a reducing, and a lysis agent such as saponin is
added while the healthy red blood cells will tend to break down quickly. In solution, the
defective red blood cells will cause a suspension to form and collect as the top layer of the tube
(Serjeant et al., 2013).
The diagnosis of sickle cell disease involves performing hemoglobin electrophoresis test.
This test involves the use of electrical current to influence the motility of the red blood cells.
Since the different type of hemoglobin has separate charges and speeds of movement along an
electric field, it will be possible to identify their various types by the two characteristics. The
quantity of each type of hemoglobin will be determined. If the number of normal hemoglobin is
below normal or there is the presence of defective hemoglobin, then sickle cell disease is evident
(Yawn et al., 2014). This test has proved very useful as a prenatal test for parents; test to check
health safety of athletes and test for the neonate’s compulsory in the US. One might have
defective hemoglobin without symptoms, but this test provides information about this.
Additional tests that can be performed are the peripheral blood smear and the liver function tests.


On the imaging tests, MRI is usually done for timely checking of the bone marrow changes
which occur because of acute and chronic bone marrow aplasia or necrosis. CT scan is also done
when not possible to detect osteonecrosis through MRI or as a safer way for patients with
hematuria to prevent medullary carcinoma. Nuclear medicine scanning is useful when checking
for early bone cell degeneration while trans-cranial ultrasound identifies when there is an
elevated risk for stroke. The abdominal ultrasonography is instrumental in checking for biliary
obstruction due.
How Genetics Can Influence Policy Issues
FDA is an agency in the US, which was set and mandated to evaluate all consumer
products in the form of food and drugs for human safety and efficacy on the indicated potential
uses. The reason for its regulatory measure is primarily to ensure health safety of the public.
According to the FDA, drugs are either classified as New Drug Application (NDA) or
Abbreviated New Drug (AND) such as a generic drug. To develop a new drug study using
laboratory animals is first done before humans are used to testing for the efficacy (Wu et al.,
2016). The FDA will involve a different agency to evaluate the quality and potential risks of the
drug. The drugs and other products require labeling on the uses of the product and the risks
together with mitigation measures in case risks (Origin, 2013).
There is controversy in the allocation of resources for funding and supporting scientific
research and study on sickle cell disease. Some say that capitalism is more superior to socialism,
but it has been evident that when organizations or people make donations of money and give
grants for studies in science. Advancements in the management of the sickle cell disease require
increased funding. Previous scientific research on sickle cell disease has led to the discovery of


several treatment approaches for sickle cell disease all over the world, including Sub-Sahara
Africa. Therefore, mobilization of resources greatly affects the success of the treatment and
management of sickle cell disease (Stephen, 2012).
Codes of conduct in health profession dictate that confidentiality should be practiced.
However, family needs to be involved in decision making regarding the health care of its
members at times especially when dealing with minors and the psychiatric and mentally
incapacitated persons. These people may not be able to make decisions on their own. It is also
essential so that family may be able to make an appropriate decision regarding insurance plan to
undertake. Family members can also provide palliative care in case of a lifelong disease like
diabetes, cancer or HIV/ AIDS (Bernabeo & Holmboe, 2013).
Chromosomal Analysis
The process involves counting and checking the chromosomes from the cells to ensure
that they contain the right number of chromosomes. The structure of the chromosomes is also
examined to make sure that it is normally shaped. Chromosomal analysis cannot apply to the
study of sickle cell anemia because it is impossible to detect single gene condition. The
chromosomal analysis, therefore, not indicated in the disorder because it results from the
mutation of the hemoglobin-Beta gene found in chromosome 11, which is a tinny deletion to be
detected by the process (Ware et al. 2017). Hemoglobin is responsible for transporting oxygen
from the lungs to other body parts. Regular hemoglobin (hemoglobin-A) are round shaped and
move in the blood vessels smoothly transporting oxygen to the body parts, but the abnormal
hemoglobin molecules (hemoglobin-S) assume a sickle shape (Serjeant, 2013). Thus, they clog
together forming extended rod-like arrangements that make the erythrocytes to be rigid.


Causes of the Sickle Cell Disorder
Typically, sickle cell anemia occurs as a result of mutation of the genes that form
hemoglobin (Rees, Williams, & Gladwin, 2010). Hemoglobin is a compound rich in iron that
gives blood the red color, and it is responsible for allowing the erythrocytes to carry oxygen from
the alveolus in the lungs to other body tissues and organs. “The sickle cell gene is inherited from
one generation to another in an inheritance pattern referred to as autosomal recessive inheritance.
It implies that both parents must pass the abnormal form of the gene for the child to be affected.
In other words, when only one parent passes the gene to the child, it means that the child will
only have the sickle cell trait but will not be affected by the disorder. People with normal and
defective hemoglobin will form both normal hemoglobin and some sickle cell hemoglobin, but
they will not have symptoms (Ware et al., 2017).” They will become carriers of the disorder
meaning they can pass the traits to their children. The primary cause of the disease is gene
mutation and not any other cause.
Origin of Sickle Cell Anemia
Sickle cell disorder originates from a mutation in the HBB gene (Rees, Williams, &
Gladwin, 2010). The genetic changes that lead to the disorder can be described as follows;
Hemoglobin compound contains four proteins subunits. “One of the subunits is called alpha-
globin, and the other is called the beta-globin. The HBB gene has the responsibility of informing
the body to form beta-globin. As a result, different kinds of beta-globin results from the mutation
in the HBB gene and a specific HBB gene mutation may produce a defective beta-globin called
hemoglobin-S (HbS).” Also, other versions of mutation in HBB gene can create abnormal types
of beta-globin including hemoglobin C (HBC) and Hemoglobin E (HbE). Therefore, individuals
with the sickle cell disease have at least one subunit of beta-globin replaced with hemoglobin S.


When Hemoglobin S takes the place of beta-globin, a person suffers from sickle cell anemia, and
the symptoms of the disease can be detected. Defective types of beta-globin can potentially
affect the erythrocytes causing them to take sickle shape making them die prematurely leading to
anemia (Yawn et al., 2014). Sometimes, the sickle-shaped red blood cells can stick to the blood
vessels causing severe medical complications.
The disease is characterized by the single cell gene mutation, which tends to carry an
abnormal gene, which has a sickle cell trait. The abnormal gene has one normal β chain gene
known as β A and one abnormal β chain gene, β S as well as a single gene. These cells have two
types of hemoglobin, which are the normal α 2 β 2 together with the sickle cell α 2 β 2 s . In this case,
the situation is known as the sickle cell trait. Individuals who have inherited the β S gene from
both the father and the mother can only make the cell hemoglobin, and this means that their
hemoglobin contains the sickle cell diseases with a single-cell form of inheritance.
Gene Mutation of the Disease
Gene mutation is the main cause of sickle cell anemia. It is a disease that can only be
inherited and not acquired. Mutation in the gene responsible for the formation of hemoglobin
causes the disease and individuals with two sets of the sickle cell can manifest the symptoms of
the disorder whereas people with an only single copy of sickle cell do not manifest the symptoms
of the disease but can pass the gene to their offspring. The mutations that result in sickle cell
anemia have been studied extensively. The effects of mutation can be traced from the DNA to
the entire organism. Although a person with a single copy of sickle cell does not have the
disease, it still affects her cells, and her proteins (Hoban et al. 2015). The figure below shows the
effects of mutation at the DNA level and the protein level.


Mutation in HBB gene is a series of causation. The changes happening in the DNA level
continue to occur until the whole organism is affected eventually (Ware et al. 2017). This shows
that a single mutation can have a large effect on the organism and its offspring. The main fact is
that even if the mutation is a mall or large, its effects can spread gradually until the whole
organism is affected.
It can be concluded that sickle cell disease is among the commonly inherited diseases. It
affects people with two copies of the defective beta-globin. The disease is fatal and can lead to
early mortality among the affected people. Sickle cell anemia is purely a disease of gene
Genetics and Policy Issues
According to the World Health Organization (WHO), genetics involves the inheritance of
characteristics from the parent to the offspring. Policymaking consists of the development of
guidelines, pursued by the government and its agencies and which guide the provision of specific
services, for instance, healthcare (Yawn et al., 2014). The advancement of biotechnology has led
to several discoveries pertaining genetics including; ability to develop an individual genetic
mapping, ability to genetically modify genetic makeup of an organism for therapeutic purposes
and discovery of genetically related diseases. Firstly, genetics determines the development of
policies preventing discrimination. The advancement of biotechnology has made it possible for
determination of an individual’s genetic makeup. If the individual is susceptible to genetic
diseases, and potential employers access the information, such individuals are at risk of
discrimination. Therefore, policymakers, through public participation should develop legal
frameworks that prevent access to individuals’ information regarding their genetic susceptibility
to medical conditions. Additionally, research on human genetics can influence policymaking.


Testing genetically modified foods and drugs and other therapeutic methods are conducted on
human subjects as the study of genetics advances; human subjects are at risks of injury and harm.
Although there are general principles that guide the conduction of research using human
subjects, there is a need to be specific with ethical and legal guidelines specifically for genetic
research involving human subjects. Additionally, currently, there exist several diagnostic and
therapeutic techniques that are based on human genetics. Therefore, policies that facilitate access
to the information and resources relating to services on genetic mapping, counseling, and
treatment should be put into place. An increase in the number of resources allocated for this
purpose should be guided by public policy developed through public participation (Botkin et al.,
Nutritional Influences for Sickle Cell Anemia
The nutrition and the development of sickle cell disease have been associated in several
clinical studies. Laboratory assessments of individuals diagnosed with the sickle cell disease
have shown reduced amounts of vitamins B6 and E in these subjects. Besides, the
supplementation of folic acid in the treatment of persons with sickle cell disease has shown
improvements in the oxygen-carrying capacity of the red blood cells and the gradual and
eventual improvement of the associated clinical signs and symptoms. In sickle cell disease, the
abnormally shaped cells are rapidly broken down in the spleen, and thus, their half-life is sixteen
to twenty days, against the normal lifespan of one hundred and twenty days. The rapid hemolysis
process may lead to the enlargement of the spleen. The enlargement of the spleen may be treated
with splenectomy. In other words, the functioning of the spleen in sickle cell disease individuals
is adversely affected. The spleen plays an immune role in the production of immune cells and
also in the recognition and destruction of pathogenic cells and particles. Therefore, sickle cell


patients require sufficient vitamins for the prevention of infections associated with sickle cell
disease. Besides, the clinical symptoms of sickle cell disease lead to the occlusion of small blood
vessels by the abnormally shaped red blood cells. When patients are dehydrated, the blood
plasma loses most of the water content. Therefore, the blood becomes thick and the bold red cells
can easily stick to one another, thereby occluding the blood vessel and causing sickling crises
and destruction of the blood vessel endothelium (Ohemeng and Boadu, 2017).
Nutritional Assessment and Counseling
Nutritional assessment is the process of collecting data and information regarding an
individual’s dietary intake and the nutritional status of the body for prevention, diagnosis, and
management of nutrition-related medical conditions. Nutritional assessment is undertaken
through various steps. The different nutritional assessment methods used are the dietary history
taking, anthropometric measurement, biochemical tests and clinical data. Dietary history taking
involves getting subjective data from the client on the nutritional composition, the amount and
the method of preparation of the food they have taken within the last 24 hours. Dietary recall
helps in determining the amount and the nutritional value of the food recently taken. The data
helps in identifying deficiencies in the nutritional composition of the meals, and the potential
nutritional deficiencies that the patient is at risk. The nutritionist can advise and take preventive
measures on the nutritional risk issues, for instance, advice on the proper diets. Anthropometric
measurements include measurements of the skinfold thickness, mid-upper arm circumference,
height, weight and calculation of body mass index. These measurements are indicators of the fat
and caloric content in the body. Therefore, the measurements can diagnose inadequate dietary
intake or excessive dietary intake in affected individuals. Thus, the results of the measurements
can be used for prevention of dietary related medical conditions or the diagnosis of nutrition-


related conditions. Clinical history involves taking information regarding any already diagnosed
medical conditions, treatment procedures for example surgical procedures and ongoing
pharmacological treatment. Information on any current medical condition helps in identifying the
etiologies of current nutritional concerns, for instance, malabsorption disorders explain
deficiency of certain nutrients and treatment procedures, and gastrostomy affects the absorption
of some nutrients from the stomach. (Tang, Quick, Chung, & Wanke, 2015).
Prevalence Rates, Testing, Treatment, and Prognosis
Sickle cell anemia affects approximately one hundred thousand Americans. The
prevalence rates are in individuals of African American descent and Hispanic origin. However,
apart from the original background as a factor that affects the prevalence of sickle cell trait, the
prevalence is affected by the nutritional status of the individuals. Specifically, in the individuals
diagnosed with nutritional deficiencies, for instance, individuals presenting with vitamin and
micronutrient deficiencies, the incidence of sickle cell disease increases by approximately 20%.
Also, the method used to test for sickle cell disease is affected by human nutrition. In individuals
presenting with symptoms suggestive of sickle cell anemia, the laboratory testing of lipid and
micronutrient profiles are some of the testing procedures to undertake. In patients diagnosed with
sickle cell disease, the treatment involves dietary supplementation with adequate amounts of
water in the food and sufficient nutrients to boost the body immunity against potential infections
(Yawn et al., 2014).
Ethical Considerations
The most common ethical dilemmas faced in the diagnosis of the sickle cell anemia
revolve around genetic screening. Since the condition is genetically inherited from the parents to
the offspring, the diagnosis of the disease can be safely conducted through prenatal screening.


There are only two available methods of carrying out the prenatal screening, and that is through
amniocentesis and chorionic villi blood sampling. The samples obtained through the procedures
mentioned above are genetically mapped to identify the presence of the amino acid valine, which
leads to sickle cell disease. If the fetus is positively diagnosed with sickle cell disease, one of the
options is to terminate the pregnancy. The ethical decision whether to terminate the pregnancy is
associated with psychological, emotional, cultural and religious considerations. The decision to
terminate the pregnancy, that is abortion, is viewed as a means of avoiding suffering and
economic burden to the child who would be born with the condition. Sickle cell is characterized
by the impairment of the red blood cells’ ability to carry and deliver enough oxygen to the
peripheral body tissues and is also characterized by sickling crisis that causes pain. Therefore, a
decision to terminate the pregnancy is viewed as a means of avoiding such physical and
psychological suffering of the positively diagnosed fetus after birth. Additionally, the
management approaches to the sickle cell disease are expensive (Benn & Chapman, 2016).
Therefore the termination of the pregnancy for positively diagnosed fetuses is a means of
avoiding the economic burden imposed in the clinical management of the condition. On the
other, termination of the pregnancy is a denial of the baby a chance to live. Pre-implantation
screening of the embryos and the subsequent destruction of positively diagnosed embryos face
the same ethical dilemmas. Furthermore, the amniocentesis and the chorionic villi blood
samplings are invasive procedures and are faced with the risk of abortion. Therefore, the decision
to carry out the procedure is faced with the challenge of risking unnecessary abortion to a fetus
that could potentially be negatively diagnosed for sickle cell anemia or carrying the procedure to
identify fetuses that are at risk of sickle cell anemia. Moreover, the issue of autonomy of the
parents emerges; the choice whether or not undertake the procedure of screening the fetus for


sickle cell anemia should be solely made by the parent. The principle of justice for the patient
should be adhered to; for the parents who refuse the sickle cell anemia screening, the baby who
turns out positive for the condition after birth should be offered the best medical care which is
due for them (Gekas, Langlois, Ravitsky, Audibert, van den Berg, Haidar, & Rousseau, 2016).
Genetics, Outcomes, and Cost
Sickle cell anemia is a genetically acquired condition; thus the best interaction is based
on genetics. Screening for the sickle cell anemia should be done through genetic testing for the
couples before conception. The couple is undergoing genetic mapping to identify the genotype of
the couple for the presence of the gene that leads to the sickle cell condition. A recessive gene
causes sickle cell disease. Therefore, a baby can only exhibit the symptoms of the sickle cell
disease when it has both the allies of sickle cell disease. The parents can be asymptomatic for
sickle cell disease when none of them has the recessive gene that causes sickle cell condition.
However, if both the parents have the recessive gene for the condition, there is probability thy
one or several of their children will be positive for sickle cell disease if they inherit both the
recessive alleles for the disease from each of the parents. Therefore, genetic mapping of couples
that have a family history of the condition is key in preventing the occurrence of the condition
(Piel, Rees, & Williams, 2014). After genetic mapping, couples undergo genetic counseling
during which; if the couple has been identified to have the potential of giving rise to a child
positive for sickle cell disease, the alternative for getting a child are explored, for instance,
adoption. Genetic screening and counseling reduce the possibility of giving birth to a baby who
is positive for sickle cell disease. The management of sickle cell disease includes bone marrow
transplantation and immediate blood transfusion for neonatal diagnosed with the condition. Early
screening of sickle cell disease has been shown to reduce the mortality rate of sickle cell disease


by 20%. The success of bone marrow transplantation for neonates who have been diagnosed with
the condition in the first five days of life have shown 80% success rate. Also, the cost of treating
the sickle cell disease is approximately 27,000 United States dollars annually. Thus, pre-
implantation and pre-conception screening and counseling would reduce the cost of managing
the condition significantly (Robinson & Fuchs, 2016).
Changes in Approaches to Care
The approaches to the care of sickle cell disease are changing from clinical management
involving bone marrow transplantation, blood transfusion, and sickling crisis into preventive
measures through pre-implantation and prenatal screening and counseling approaches (Gibbons,
Geoghegan, Conroy, Lippacott, O’Brien, D., Lynam, & McMahon, 2015). The new approaches
are cost-effective, and have evidence of the increased quality of care and therefore improved
clinical outcomes with associated improvement in the quality of life and reduction of the
mortality rates (Mnika, Pule, Dandara, & Wonkam, 2016).
Educating Colleague and Patients
Firstly, individuals should be educated on the type of the disease, including information
that the disease is genetically inherited. Besides, the education to individuals will create
awareness on the significance of genetic screening to prevent bearing children who are positive
for sickle cell anemia (Gomes, Andrade Barbosa, Vieira, Castro, Caldeira, Torres, & Viana,
2017). I addition, individuals should be encouraged on undergoing genetic counseling
concerning the risk of genetically passing the condition to their offsprings (Gibbons, Geoghegan,
Conroy, Lippacott, O’Brien, D., Lynam, & McMahon, 2015).


In conclusion, the sickle disease is a genetically inherited medical condition. The
condition affects a significant population in the USA. The clinical symptoms and the course of
the disease cause serious health concerns. To achieve successful management approaches for
sickle cell anemia, sufficient resources are required to support scientific research to update the
treatment of sickle cell disease. Concerns surrounding genetics should be taken into
consideration while developing policies to address the underlying economic and social concerns.
Sickle cell anemia is significantly influenced by the nutritional intake and status of the affected
individual. The prevalence and treatment of sickle cell disease are mostly affected by the
underlying nutritional relevance to the condition. Several ethical issues result in ethical dilemmas
concerning the screening of sickle cell anemia. The dilemmas are primarily in deciding whether
to destroy embryos those are have been positively diagnosed with sickle cell disease or
termination of pregnancy in which the fetus has been diagnosed with the gene for sickle cell
disease. Early genetic screening and counseling improve the quality of life and reduces mortality
rates for individuals diagnosed with sickle cell anemia. The new approaches to the management
of sickle cell anemia involve the early screening, and therefore education to the general pupation
aims at creating awareness on the significance of genetic screening and counseling.



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Yawn, B. P., Buchanan, G. R., Afenyi-Annan, A. N., Ballas, S. K., Hassell, K. L., James, A. H.,
& Tanabe, P. J. (2014). Management of sickle cell disease: summary of the 2014
evidence-based report by expert panel members. Jama, 312(10), 1033-1048.
Yawn, B. P., Buchanan, G. R., Afenyi-Annan, A. N., Ballas, S. K., Hassell, K. L., James, A. H.,
… & Tanabe, P. J. (2014). Management of sickle cell disease: summary of the 2014
evidence-based report by expert panel members. Jama, 312(10), 1033-1048.
Yawn, B. P., Buchanan, G. R., Afenyi-Annan, A. N., Ballas, S. K., Hassell, K. L., James, A. H.,
… & Tanabe, P. J. (2014). Management of sickle cell disease: summary of the 2014
evidence-based report by expert panel members. Jama, 312(10), 1033-1048.

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