NATIONAL UNIVERSITY FAIRVIEW

“SICKLE CELL ANEMIA”

GENERAL BIOLOGY 2

12STEM2306

BLANCO, SOPHIA ASHANNA I.

CARDONA, CRISAILA

CASTRO, LOURD CARY

MABALOT, ANREI NICOLE

MAGCAMIT, KIRSTEL ALONA A.

TAGUBA, HANNAH MAY A.

FEBRUARY 27, 2024

Page | 1
 TABLE OF CONTENTS

I. INTRODUCTION………………………………………………………………………… 3

II. HISTORY…………………………………………………………………………………... 4

III. DESCRIPTION OF THE DISORDER…………………………………………………… 4

IV. GENETIC BASIS…………………………………………………………………………... 5

V. INHERITANCE PATTERN……………………………………………………………….. 5

VI. PREVALENCE……………………………………………………………………………... 6

VII. SYMPTOMS AND EFFECTS……………………………………………………………... 7

VIII. DIAGNOSIS AND TREATMENT………………………………………………………… 8

IX. CONCLUSION AND/OR RECOMMENDATION………………………………………. 11

X. REFERENCES……………………………………………………………………………... 14

Page | 2
 I. INTRODUCTION
Evolutionary change cannot occur without genetic inheritance. In genetics, the term "inherited"
pertains to the traits or variants coded in DNA that are transferred from parent to offspring during
reproduction (Inherited, 2024). Inheritance of traits or characteristics, including eye color and blood
type, from parents to their offspring occurs through genes. Certain health conditions and diseases can
also be inherited genetically. Additionally, some traits have multiple forms, such as blood type, which
can be classified as A, B, AB, or O (Department of Health & Human Services, n.d.). The rules of
Mendelian genetics determine how inheritance occurs. Genetic inheritance, also known as heredity, is
process fundamental to biology and is responsible for the diversity of life on Earth. The study of genetic
inheritance has made significant contributions to our understanding of human health, disease, and
evolution. Learning about genetic factors and disorders is crucial in promoting health and preventing
diseases. Certain genetic changes have been linked to an elevated risk of having a child with a
developmental disability or birth defect, as well as the development of health conditions like cancer and
heart disease. By understanding these genetic factors, we can take proactive measures to reduce our risk
of developing these conditions and promote better health outcomes (Genetics Basics | CDC, 2021).

According to Mangla (2023), Sickle Cell Anemia is a hereditary condition that affects the
globin chains, leading to hemolysis and ongoing harm to various organs. Sickle Cell Disease (SCD) is
a prevalent blood disorder that causes hemolytic anemia, leading to painful episodes, harm to organs,
and the need for blood transfusions throughout a person's life. It has a significant impact worldwide,
particularly among people with ancestral roots from sub-Saharan Africa, Spanish-speaking regions in
the Western Hemisphere, Saudi Arabia, India, and Mediterranean countries such as Turkey, Greece, and
Italy (Data & Statistics on Sickle Cell Disease | CDC, 2022). Sickle Cell Disease is caused by a mutation
in the hemoglobin gene that results in the production of abnormal hemoglobin. This abnormal
hemoglobin causes red blood cells to become rigid, sticky, and crescent-shaped, which can lead to a
host of health problems, including pain, organ damage, and an increased risk of infections (Mangla,
2023). There are several types of sickle cell disease. The most common are Sickle Cell Anemia (SCA),
Sickle Hemoglobin-C Disease (SC), Sickle Beta-Plus Thalassemia and Sickle Beta-Zero Thalasse.

Sickle cell anemia (SCA) is the most severe form of SCD. Sickle cell anemia is an inherited
disease that results from a defect in a gene that codes for the production of hemoglobin - the protein
responsible for carrying oxygen in the blood. Symptoms of sickle cell anemia can manifest at different
ages and vary from person to person, with changes in symptoms being possible over time. However,
typically, symptoms of this condition tend to appear around the age of six months (Sickle Cell Anemia

Page | 3
- Symptoms & Causes - Mayo Clinic, 2022). Normally, red blood cells live for about 120 days before
they die and are replaced by new ones. However, in sickle cell anemia, the abnormal crescent-shaped
red blood cells tend to have a shorter lifespan of about 10 to 20 days. This is because these sickled cells
are stiff, fragile, and prone to breaking apart easily. As a result, they may get stuck in small blood vessels
and cause blockages, which can lead to reduced blood flow and oxygen supply to various organs and
tissues in the body. The spleen, an organ that helps filter the blood of infections, may also be affected
by sickle cell anemia. Sickled cells can get trapped in the spleen's filter and die, causing damage to the
organ. This can put individuals with sickle cell anemia at a greater risk of infections and make them
more susceptible to becoming chronically anemic due to the reduced number of healthy red blood cells
circulating in the body (Sickle Cell Disease, 2019).

II. HISTORY
A particular kind of hereditary disorder called sickle cell anemia is distinguished by Aberrant
Hemoglobin. Known as "sickle shaped red blood cells," they were created in 1910 by James B. Herrick,
who identified a certain blood condition, although at the time, it was not recognized as a disease.
Furthermore, Verne Mason developed the term "sickle cell" in 1922, which contributed to the
standardization of the condition's name in the field of medicine. This phrase made it easier for
researchers and healthcare professionals to collaborate and communicate. In addition, researchers
discovered in 1940 that Priceley hemoglobin S (HbS), an aberrant form of hemoglobin, is a hereditary
disorder. Nine years later, in 19494, Linus Pauling and his research group identified the aberrant
hemoglobin associated with the illness. Understanding how the genetic mutation caused the
characteristic amputation of red blood cells in sickle cell anemia patients was improved by the
identification of hemoglobin S's molecular structure. In 1956, Vernon Ingram, a biochemist, identified
variations in amino acids in the hemoglobin of affected patients and used this knowledge to figure out
the chemical basis. Through his studies, the genetic and molecular aspects of the disease are explained
in great depth. (Johns Hopkins University, 2023)

III. DESCRIPTION OF THE DISORDER

Sickle cell disease encompasses a collection of hereditary conditions impacting the red blood
cells, which are responsible for transporting oxygen throughout the body via the hemoglobin protein.
While healthy red blood cells are typically pliable and disc-shaped, individuals with sickle cell disease
experience a genetic mutation causing their red blood cells to adopt a crescent or sickle shape. This
alteration renders the cell less flexible and prone to obstructing blood flow, potentially leading to
complications in various bodily systems. Sickle cell disease is also known as a lifelong disease.

Page | 4
 Sickle cell anemia symptoms typically emerge around six months of age, though they can vary
between individuals and evolve over time. In this condition, abnormal crescent-shaped red blood cells
have a shortened lifespan of 10 to 20 days, compared to the usual 120 days. These cells are rigid, fragile,
and prone to clotting in small blood vessels, leading to reduced blood flow and oxygen delivery to
organs and tissues. The spleen, responsible for filtering blood, can also be affected, increasing the risk
of infections and chronic anemia due to decreased healthy red blood cell count.

IV. GENETIC BASIS

Genetic inheritance operates on the principle of receiving genes in pairs, with one set inherited
from each parent. The occurrence of sickle cell disease in a child typically arises when both parents
possess the sickle cell genetic, commonly referred to as being carriers of the sickle cell trait.
Alternatively, the condition can manifest if one parent has sickle cell disease while the other carries the
genetic for it. This genetic interplay underscores the importance of understanding familial health history
and genetic predispositions in assessing the risk of inherited conditions like sickle cell disease.

V. INHERITANCE PATTERN
Sickle cell anemia is an inherited blood disorder that affects the production of hemoglobin, the
protein that carries oxygen in the red blood cells. The inheritance pattern of sickle cell anemia is
autosomal recessive, which means that a child must inherit two copies of the abnormal hemoglobin
gene (one from each parent) to develop the disease. If a person inherits only one copy of the abnormal
gene, they will have sickle cell trait (Sickle Cell Disease: MedlinePlus Genetics, 2020). A mutation in
the HBB gene causes sickle cell anemia, a genetic disorder that runs in generations. In sickle cell
anemia, the development of hemoglobin S (HbS), an aberrant form of hemoglobin, has emerged as a
primary mutation. There must be two copies of the defective gene called HBB for a person to develop
sickle anemia, which is inherited in a recessive fashion. The hemoglobin allele that reflects HbA is
called normal hemoglobin (Hba). HbA/HbA, the normal allele, is present in two separate people who
do not get sickle cell anemia and have normal hemoglobin levels. Furthermore, hemoglobin S (HbS),
which is donated as HbS, is a mutant hemoglobin allele. There are two copies of the mutated gene
(Hbs/Hbs) that results in abnormal hemoglobin S and is affected by sickle cell anemia. The carrier state
(HbA/Hbs), commonly referred to as heterozygous carriers of the disease or carriers of the sickle cell
trait, consists of one mutant cell (HbA/HbS) and one normal allele. (Eman A. Ajjack, et al)

Page | 5
 VI. PREVALENCE
Children are most affected by sickle cell disease mortality, particularly in nations with the
highest rates of death for under-5-year-olds, according to a study of The Lancet Group. Globally, about
300,000 babies are born with sickle cell disease (SCD) each year. However, since more than 75% of
SCD cases are found in Sub-Saharan Africa, this SCD population makes up just 1% of all SCD cases
worldwide (Makani, J., Ofori-Acquah, S. F., Nnodu, O., Wonkam, A., & Ohene-Frempong, K., 2013).
The impact of sickle cell disease on global public health is significant and continues to grow. By
estimating the birth prevalence of afflicted children, the prevalence of SCD can be objectively
identified; however, this requires precise diagnosis and registration at birth. In Sub-Saharan Africa, the
increased rate could be because of possible additional effects from migration that are difficult to
measure due to data lags and the lack of universal newborn screening which identifies conditions that
can affect a child's long-term health or survival. (GBD 2021 Sickle Cell Disease Collaborators*, &
analyses, S. global, 2023).

However, this could also occur depending on the gene of a parent. According to
Hematology.org, Sickle cell disease affects between 70,000 and 100,000 people in the United States.
Affected people have this disease from birth, which results in aberrant hemoglobin production. Both
parents must have sickle cell disease (two sickle cell genes) or sickle cell trait (one sickle cell gene) for
a person or a child to inherit sickle cell disease. A parent will give one sickle cell gene to their offspring
if they have sickle cell disease.

Sickle cell trait and sickle cell disease are different. Sickle cell trait is an inherited blood
disorder that affects approximately 8 percent of African-Americans. Unlike sickle cell disease, in which
patients have two genes that cause the production of abnormal hemoglobin, individuals with sickle cell
trait carry only one defective gene and typically live normal lives without health problems related to
sickle cell. But both could be the inheritance of genes (Hematology.org., n.d.).

SCD is thought to cause the annual loss of millions of years of disability-adjusted life
expectancy, especially in developing nations. Therefore, there is an urgent need for routine and ongoing
surveillance efforts, additional research to determine the role of conditions related to sickle cell disease,
and widespread implementation of evidence-based prevention and treatment for sickle cell disease
patients due to widespread data gaps and correspondingly high uncertainty in the estimates.

Page | 6
VII. SYMPTOMS AND EFFECTS

SYMPTOMS OF SICKLE CELL ANEMIA

Splenic sequestration. Increasing risk of RBCs becoming entrapped in the spleen,

stemming from diminished splenic filtering function from early childhood.

Susceptibility to infection. Vulnerability to pathogens such as pneumococcus and

salmonella arises from impaired splenic function.

Jaundice. This presents as hyperbilirubinemia and yellowish discoloration of the skin

and eyes, caused by excessive hemolysis overloading liver pathways.

Priapism in males. Prolonged painful erections can occur from sickling within penile
blood vessels.

Fatigue. Chronic anemia leads to weakness and reduced exercise tolerance.

Delayed growth in children. Growth retardation in pediatric patients may result from
repetitive anemia and impaired development.

Hand-foot syndrome in young children. This appears as painful swelling of the

extremities as bones develop.

Organ damage to lungs, kidneys, liver, heart, eyes

Pulmonary hypertension

Stroke

Avascular necrosis of bone

Leg ulcers

Page | 7
 Delayed sexual maturation

Reduced life expectancy

Cognitive deficits

Osteoporosis

Growth impairment during childhood

Additional Effects:
Ocular complications like retinal damage

Pregnancy complications in females

Silent strokes

VIII. DIAGNOSIS AND TREATMENT

Diagnosis:

Sickle cell anemia is typically diagnosed through a combination of medical history, physical
exam, and laboratory testing. Doctors evaluate for symptoms and perform blood tests to detect abnormal
hemoglobin variants. Specifically, hemoglobin electrophoresis/HPLC identifies the presence of
hemoglobin S (HbS), confirming the diagnosis of sickle cell anemia.

Diagnosis Procedure:

Clinical Evaluation. A comprehensive medical history and physical examination are conducted
to identify symptoms and signs associated with sickle cell anemia.

Laboratory Testing. Hemoglobin electrophoresis or HPLC is performed to detect abnormal

hemoglobin variants, primarily HbS. Molecular genetic testing is used to confirm the specific HBB
gene mutation responsible for sickle cell anemia.

Treatments:

Pain management with analgesics. Analgesics are used to relieve acute pain episodes that
individuals with sickle cell anemia may experience.

Page | 8
 Hydroxyurea to increase fetal hemoglobin production. Hydroxyurea is prescribed to
stimulate the production of fetal hemoglobin, which helps prevent the formation of sickle-shaped red
blood cells.

Infection prevention with antibiotics. Antibiotics are given to prevent and treat infections, as
individuals with sickle cell anemia are more prone to bacterial infections.

Blood transfusions. Administered for anemia to improve oxygen delivery and alleviate
symptoms.

IX. RESEARCH AND DEVELOPMENTS

The current advances in therapy for sickle cell anemia:

1.1. Modifying the patient’s genotype

An 8-year-old child with SCD and frequent exposure to VOCs was the first patient to have her
genotype modified via hemopoietic stem cell transplantation (HSCT) over 30 years ago; the child went
on to develop acute myeloid leukemia as a result. Her sickle cell complications also resolved at the
same time that her leukemia was cured (Johnson et al., 1984; Johnson, 1985). Up until that point, HSCT
was not thought to be a possible treatment for SCD. It made bone marrow transplantation (BMT) a
viable treatment option for kids with severe sickle cell disease (SCD) (Walters et al., 1996b).

Allogeneic Bone Marrow Transplant

Stem cell transplantation, or BMT, is the only treatment for sickle cell disease that has been
proven to work. It substitutes healthy stem cells for the sick ones that form blood. SCD is treated with
allogeneic transplantation. In this type of transplant, the cells that produce defective hemoglobin are
replaced with healthy cells donated by a third party. These sound cells can be obtained from umbilical
cord blood, unrelated donors, or family members. To begin with, patients will receive chemotherapy
(chemo) to destroy the cells that produce defective hemoglobin. Then, much like with a blood
transfusion, the healthy cells are administered to them via an intravenous (IV) catheter. While organ
damage cannot be undone, transplantation can prevent additional harm from occurring
(BeTheMatch.org., n.d.).

Currently there are about 35 clinical trials at ClinicalTrials.gov studying allogeneic BMT in
patients with SCD. One of the main limitations, unfortunately, is the low probability of finding suitable
donors for African and African American populations as per the National Marrow Donor Program and
so, not sufficient MUD transplants have been completed in patients with SCD (Salinas Cisneros, G., &
Thein, S. L., 2020).

Autologous Hematopoietic Stem Cell

Page | 9
 Nowadays, hematopoietic stem cell transplantation (HSCT) is a significant therapeutic option
for SCD patients. According to Walters et al. (2010), HSCT can establish donor-derived erythropoiesis,
but more significantly, when done on time, it can stabilize or even restore function in the affected organs
of SCD patients.

However, autologous HSCT is ineffective for sickle cell disease (SCD) unless the underlying
genetic mutation has been corrected in the stem cells through genetic modification. As the process of
hematopoietic stem cell transplantation is intricate and requires a lot of planning and multiple tests. In
autologous transplants, the patient is their own donor because the stem cells are taken from the same
individual receiving the transplant while allogeneic transplants use stem cells from a donor—either an
unrelated or matched relative—rather than the patient. To maximize these results, though, this work
must be expanded outside of the transplant center to community-based pediatric and adult hematologists
in order to ensure that affected patients are referred when it is most appropriate for HSCT evaluation.
It is imperative to raise awareness of this therapeutic option among hematologists who provide care for
patients with sickle cell disease (SCD). The actions most likely to enhance patient outcomes and safety
are increasing access to HSCT and carrying out research into how to make it safer and more effective
for patients with SCD (Ashorobi, D., 2023).

Gene Therapy
In some patients, a single dose of an experimental gene therapy for sickle cell disease eliminated
the disease's most serious complication for at least three years and returned blood cells to their normal
shape. Tested on 35 adults and adolescents with sickle cell disease, the single-dose therapy not only
completely eliminated episodes of excruciating pain that arise from the rigid, crescent-shaped red blood
cells clumping together and blocking blood vessels, but it also effectively corrected the shape of the
patients' red blood cells. The patients who have a closely matched sibling donor have the best chance
of recovering from this illness. Blood is drawn from the patient to extract blood-forming stem cells
using the novel gene therapy known as Lentiglobin. The modified beta-globin gene is then introduced
into the stem cells using safe lentiviruses. Upon being reinfused into the patient, the cells settle in the
bone marrow and begin producing new, healthy red blood cells. One drawback of gene therapy is that
patients have to undergo high-dose chemotherapy beforehand in order to induce the death of old stem
cells and create space for the altered stem cells—a procedure called conditioning. Chemotherapy carries
a slight risk of cancer and can be toxic. Leukemia struck two trial participants, and the researchers
believe this was caused more by the chemotherapy than by the Lentiglobin treatment. Presently,
scientists are investigating less hazardous methods for priming the bone marrow prior to gene therapy
(Columbia University Irving Medical Center., 2021).

Page | 10
 Gene Editing

With regulatory approval, CRISPR, the gene-editing technology that has transformed biological
research, is now available as a medical treatment. December 8th, the U.S. The Food and Drug
Administration authorized the first sickle cell disease CRISPR treatment. Exa-cel directs the Cas9
enzyme to the BCL11A gene, which normally stops the body from producing a type of hemoglobin that
is exclusive to foetuses. By snipping the DNA of BCL11A, Cas9 deactivates the protein in bone marrow
stem cells, which is responsible for producing red blood cells with a normal round shape and foetal
hemoglobin. The novel treatment involves taking out the patient's own bone marrow stem cells, editing
them with exa-cel, destroying the remaining, untreated bone marrow, and then injecting the edited cells
back into the patient. 29 out of 30 study participants with sickle cell anemia experienced no pain for a
full year in these ongoing trials. The FDA was notified of results that indicate exa-cel does not appear
to have any significant negative effects on health, despite the possibility of side effects like fever and
nausea. However, DeBaun notes that issues might surface later because the participants have only been
monitored for a brief period of time (Reardon, S., 2023).

1.2 Targeting the cause

According to Salinas Cisneros, G., & Thein, S. L., treatment that targets the hemoglobin S
polymerization, vas occlusion, and inflammation—all of which can be the underlying causes of sickle
cell anemia—can be used as a therapy for treatment. Addressing the mechanisms that led to the
development of sickle cell anemia, could be seen as a kind of prevention that will lessen the damage it
will eventually cause rather than completely stop it. Nevertheless, because new drugs and technologies
are needed to carry out these treatments, they remain flawed. Since there has been less focus on
examining the various ways in which fiber formation can be inhibited, clinical trials are still ongoing.

X. CONCLUSION AND/OR RECOMMENDATION

Sickle cell anemia is a genetic disorder characterized by the abnormal shape of red blood
cells, leading to various complications such as pain crises, anemia, organ damage, and increased
susceptibility to infections. It significantly impacts the quality of life of affected individuals and their
families. In conclusion, adopting a comprehensive approach to managing sickle cell anemia is
paramount. This approach encompasses early diagnosis, multidisciplinary care, disease-modifying
therapies, effective symptom management, robust psychosocial support, and ongoing research
advancements. Such a holistic strategy is indispensable for enhancing outcomes and elevating the
quality of life for individuals living with this condition.

Page | 11
 Recommendations:

- Genetic and Molecular Studies:

- Investigate the genetic and molecular mechanisms of sickle cell anemia for targeted therapy
development.

- Novel Treatment Approaches:

- Explore innovative treatments like gene therapy and CRISPR-Cas9 to address sickle cell disease's
genetic defects.

- Improved Symptom Management:

- Research new strategies, including non-pharmacological interventions, for better pain management
in sickle cell anemia.

- Early Intervention and Screening:

- Enhance early detection through expanded newborn screening programs for timely treatment
initiation.

- Psychosocial Impact and Support:

- Develop tailored support programs, such as counseling and community resources, to address the
emotional needs of patients and families.

- Healthcare Access and Equity:

- Investigate and address disparities in healthcare access and outcomes for sickle cell patients to ensure
equitable care.

- Long-Term Outcomes and Complications:

- Study long-term complications to inform comprehensive care strategies and improve patient
prognosis.

- Global Health Initiatives:

- Collaborate on global initiatives for sustainable and culturally sensitive approaches to sickle cell
disease diagnosis, treatment, and prevention in resource-limited settings.

• Early Diagnosis and Education:

o Newborn screening programs are crucial for early intervention.
o Education for patients and families about disease management is essential.

• Comprehensive Care:
o Multidisciplinary care involving hematologists, primary care physicians, and pain management
specialists is necessary.
o Regular check-ups, complication monitoring, and preventive measures are vital.

• Disease-Modifying Therapies:

Page | 12
o Hydroxyurea and other treatments effectively reduce complications.
o Ongoing research into gene therapy holds promise for future treatments.

• Symptom Management:
o Comprehensive pain management strategies are essential.
o Hydration, medications, heat, and relaxation techniques can alleviate symptoms.

• Transfusion Therapy and Bone Marrow Transplantation:

o Transfusion therapy addresses complications like anemia.
o Bone marrow transplantation offers potential cures for select patients.

• Psychosocial Support:
o Counseling, support groups, and community resources benefit patients and families.

• Research and Advocacy:

o Continued research and advocacy efforts are crucial for improving outcomes and access to care.

Future researchers studying sickle cell anemia should focus on developing more effective
treatments and cures for this inherited blood disorder. Research efforts should be directed towards
understanding the genetic basis of sickle cell anemia and discovering new therapeutic targets. It is
crucial to explore the underlying molecular mechanisms of the disease to identify new treatment
approaches. Additionally, researchers should aim to improve the quality of life of individuals with sickle
cell anemia by developing better pain management strategies, reducing the risk of complications, and
improving access to healthcare. Collaborative efforts between researchers, healthcare providers,
patients, and advocacy groups are essential to advance our understanding of sickle cell anemia and
make progress towards a cure.

Page | 13
 XI. REFERENCES

Tisdale, J. F., Thein, S. L., & Eaton, W. A. (2020). Treating sickle cell anemia. Science,
367(6483), 1198-1199. https://europepmc.org/article/NBK/nbk1377

Hebbel, R. P., Belcher, J. D., & Vercellotti, G. M. (2020). The multifaceted role of
ischemia/reperfusion in sickle cell anemia. The Journal of Clinical Investigation, 130(3), 1062-1072.
https://www.jci.org/articles/view/133639

Bender, M. A., & Carlberg, K. (2021). Sickle cell disease.

https://jamanetwork.com/journals/jama/article-abstract/2793821

Experimental gene therapy reverses sickle cell disease for years. Columbia University Irving
Medical Center. (2021, December 13). https://www.cuimc.columbia.edu/news/experimental-gene-
therapy-reverses-sickle-cell-disease-years

(PDF) sickle-cell disease diagnosis support selecting the most ... (n.d.).
https://www.researchgate.net/publication/344603001_Sickle-
cell_disease_diagnosis_support_selecting_the_most_appropriate_machinelearning_method_Towards_
a_general_and_interpretable_approach_for_cellmorphology_analysis_from_microscopy_images

Makani, J., Ofori-Acquah, S. F., Nnodu, O., Wonkam, A., & Ohene‐Frempong, K. (2013b).
Sickle cell disease: new opportunities and challenges in Africa. The Scientific World Journal, 2013, 1–
16. https://doi.org/10.1155/2013/193252

Cisneros, G. S., & Thein, S. L. (2021). Research in sickle cell Disease: From bedside to bench
to bedside. HemaSphere, 5(6), e584. https://doi.org/10.1097/hs9.0000000000000584

Website, N. (2023, October 3). Causes. nhs.uk. https://www.nhs.uk/conditions/sickle-cell-

disease/causes/#:~:text=To%20be%20born%20with%20sickle,having%20the%20sickle%20cell%20tr
ait.

What is sickle cell disease? | NHLBI, NIH. (2023, August 30). NHLBI, NIH.
https://www.nhlbi.nih.gov/health/sickle-cell-
disease?fbclid=IwAR1HFVVKK95RdBI1f6nCv5JcAV7wLNSt_CnpMG961WninCorPZ6cHS5_tM8
#:~:text=Normally%2C%20red%20blood%20cells%20are,the%20rest%20of%20the%20body

Sex-linked recessive: MedlinePlus Medical Encyclopedia. (2022).

https://medlineplus.gov/ency/article/002051.htm

Adigwe OP, Onoja SO, Onavbavba G. A Critical Review of Sickle Cell Disease Burden and
Challenges in Sub-Saharan Africa. J Blood Med. 2023;14:367-376. doi: 10.2147/JBM.S406196. PMID:
37284610; PMCID: PMC10239624.

Awasthi, D.K. & Kamal, M. (2023). Sickle cells Diseased-Inherited RBC Disorders. Clinical
and Laboratory Research, 1(1).
file:///C:/Users/Administrator/Downloads/Documents/1705750457Galley_Proof-
Sickle_cells_Diseased-Inherited_RBC_Disorders.pdf

Page | 14
 Bender MA, Carlberg K. (2021). Europe PMC. https://europepmc.org/article/NBK/nbk1377

Mangla, A. (2023, September 4). Sickle cell anemia. StatPearls - NCBI Bookshelf.
https://www.ncbi.nlm.nih.gov/books/NBK482164/#:~:text=Sickle%20cell%20anemia%20is%20an,pa
in%20crises%2C%20and%20organ%20damage.

Sickle cell disease. (n.d.). Google Books.

https://books.google.com.ph/books?hl=tl&lr=&id=vFfSDwAAQBAJ&oi=fnd&pg=PA13&dq=Sickle
+cell+anemia+history&ots=RqwbApHLrz&sig=nyNMUw5JcuM2Z6twkvy42sizKbQ&redir_esc=y#v
=onepage&q=Sickle%20cell%20anemia%20history&f=false

Tebbi, C. K. (2022). Sickle cell Disease, a review. Hemato, 3(2), 341–366.

https://doi.org/10.3390/hemato3020024

Wonkam, A., Chimusa, E. R., Mnika, K., Pule, G. D., Bitoungui, V. J. N., Mulder, N., Shriner,
D., Rotimi, C. N., & Adeyemo, A. (2020). Genetic modifiers of long‐term survival in sickle cell anemia.
Clinical and Translational Medicine, 10(4). https://doi.org/10.1002/ctm2.152

Story, C. M. (2018, July 14). Sickle cell test. Healthline.

https://www.healthline.com/health/sickle-cell-test. Last updated 2019

Makani, J., Ofori-Acquah, S. F., Nnodu, O., Wonkam, A., & Ohene‐Frempong, K. (2013).
Sickle cell disease: new opportunities and challenges in Africa. The Scientific World Journal, 2013, 1–
16. https://doi.org/10.1155/2013/193252

Department of Health & Human Services. (n.d.). Genes and genetics explained. Better Health
Channel. https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/genes-and-genetics

Genetics Basics | CDC. (2021.).

https://www.cdc.gov/genomics/about/basics.htm#:~:text=Understanding%20genetic%20factors%20an
d%20genetic,as%20cancer%20or%20heart%20disease.

Salinas Cisneros, G., & Thein, S. L. (2020, April 8). Recent advances in the treatment of sickle
cell disease. Frontiers.
https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00435/full

Page | 15
Page | 16