Running head: SICKLE CELL: PART II 1

Sickle Cell: Part II

Susan Kelly

King University
SICKLE CELL: PART II 2

Sickle Cell: Part II

An inherited disease, featuring sickle-shaped red blood cells (RBCs) along with clinical

manifestations resulting from the abnormal erythrocytes. Several million people are affected with

sickle cell disease. Individuals from Africa and middle east decent are those mostly affected.

Sickle cell is an inherited disease relevant to the geographical location. Genetics is the only form

of transmission for sickle cell disease.

Pathophysiology

Health care professionals have various opinions about sickle cell disease. There is much-

needed education in the public health realm on the disease process of the sickle cell.

Understanding disease process will allow health care professionals to develop a better plan of

care. The mutation accountable for the sickle cell was acknowledged as the beta S mutation,

“this mutation always consists in a T for A substitution in condon 6 of the beta-globin chain.

Deoxygenated HbS becomes polymerized, producing erythrocytes shape changes and

vasoocclusion” (Labie & Elion, 1999). There are various forms of sickle cell disease some

individuals may not exemplify signs and symptoms or may exhibit a mild form whereas other

individuals may exemplify severe forms of sickle cell disease process. How the environment

impacts sickle cell is unknown exactly, however:

genetic environmental factors that may interfere with one or more steps of the basic

pathophysiologic mechanisms. These factors can be roughly classified in three groups i)

factors that modify HbS levels with erythrocytes, thereby impacting the propensity of

HbS for polymerization; ii) other normal or abnormal hemoglobin molecule within the

polymer, thus either stopping or enhancing polymerization iii) molecules other than

hemoglobin expressed at the surface of the SCD reticulocytes that may adhere to the
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vascular endothelium, thus slowing flow in the microcirculation and delaying HbS

reoxygenation (Labie & Elion, 1999).

Understanding the pathophysiology of a disease process will foster a better patient-provider

relationship, and the provider will develop an appropriate plan of care with treatment options

based on best practice. When the provider has a better understanding, patient outcomes will be

better.

Sickle cell patients often time finds themselves in the crisis state causing severe pain due

to necrosis from decreased oxygenation as blood cannot properly flow due to the sickle shaped

RBCs, “if cerebral blood flow is inadequate, the oxygen extraction increases. Proper oxygenation

to prevent tissue hypoxemia that is poorly tolerated by brain tissue and quickly leads to ischemia

and often irreversible infarction and neurological impairment” (Strouse, 2016). This same

process also impacts all organs of the body causing infarctions and potential necrosis.

Sickle cell patients also suffer from inflammatory response more so than individuals

without sickle cell disease. During the chronic phase, there are several factors associated with the

inflammatory state such as:

endothelial damage; increased production of reactive oxygen species; hemolysis;

increased expression of adhesion molecules by leukocytes, erythrocytes, and platelets;

and increased production of proinflammatory cytokines. Genetics characteristics

affecting the clinical severity of SCA include variations in the hemoglobin F (HgF) level,

the coexistence of alpha-thalassemia, and the haplotype associated with the HbS gene

(Bandeira et al., 2014).

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Immune Response

Sick cell disease is no exception to immune response especially young children

prophylactic doses of antibiotic therapy is recommended due to the susceptibility of infection

that could be detrimental. Along with antibiotic therapy, it is imperative sickle cell patients

receive vaccinations in the recommended timeframe. Studies show:

well-characterized association between innate immunity, hemostasis, angiogenesis and

heme metabolism with SCD is also consistently observed at the transcriptomic level,

*across independent studies. The enrichment of genes and pathways associated with

innate immunity and damage repair associated pathways supports the model of erythroid

danger-associated molecular patterns (DAMPs) as key mediators of the pathogenesis of

SCD (Hounkpe et al., 2015).

Ongoing research is taking place in regards to sickle cell disease. All aspects of the disease are

not clearly identified. Immune response to the disease is no exception:

the immune system ultimately responds to HbS polymerization the initial trigger of the

pathogenic cascade of SCD. This complex immune response involves endothelial, and

coagulation activation increased cellular adhesion expression of pro-inflammatory and

8pyrogenic cytokines, neutrophil activation and increased oxidation and increased

+oxidative stress (Hounkpe et al., 2015).

All individuals diagnosed with SCD should seek medical attention at the onset of a period of

illness.

Treatments

Unfortunately, there is no known cure for sickle cell. However, research is ongoing.

Studies have suggested that “nurses should screen for insomnia symptoms and explore
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interventions to promote better sleep among adults with SCD, with an emphasis on

recommending treatment for pain and depression” (Moscou-Jackson et al., 2016). According to

The Centers for Disease Control and Prevention (CDC):

SCD is a disease that worsens over time. Treatments are available that can prevent

complications and lengthen the lives of those who have the condition. These treatment

options can be different for each person depending on the symptoms and severity ("

Complications and Treatments," 2016).

As research continues so does research related to pharmacological therapy, “the search continues

for more effective drugs to reduce sickling” (Gould & Dyer, 2011). The utilization of

hydroxyurea decreases crisis episodes and prolongs life span, however, “more than 3 of 4

patients who might benefit were not treated with this safe and inexpensive drug” (Stettler,

McKiernan, Melin, Adejoro, & Walczak, 2015). Hydroxyurea is an antineoplastic,

antimetabolite which, “acts by inhibiting DNA synthesis without interfering with RNA or protein

synthesis; incorporates thymidine into DNA, causing direct damage to DNA strands, cell cycle

specific S phase” (Skidmore-Roth, 2015). The underutilization of medications could be linked to

lack of knowledge there are so many health care providers monitoring narcotic administration

and abuse, patients with sickle cell are less likely to be treated to the fullest potential.

Individuals with sickle cell should be on a daily dose of folic acid along with avoiding strenuous

activity. High altitudes should also be avoided. Hydration is very important as is immunizations.

Individuals with severe cases of the sickle cell may benefit from prophylactic doses of penicillin

for young children to the age of five, “poor adherence to prophylactic antibiotics was related to

higher rates of infection and sickle cell pain crisis” (Loiselle et al., 2015). The age group of two

to sixteen, “transcranial Doppler examinations, and long-term transfusion therapy to prevent

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stroke in those children with abnormal transcranial Doppler velocity” (Yawn et al., 2014).

During sickle cell crisis, the utilization of opioids for treatment, “of severe pain associated with

the vaso-occlusive crisis, and use of incentive spirometry in patients hospitalized for vaso-

occlusive crisis” should be standard of care (Yawn et al., 2014). It is imperative for patients

suffering from sickle cell crisis to have pain control as ischemic phases could be taking place

throughout the body, during the crisis phase there is also an increased demand for oxygenation,

“significant rheological changes ensure with increased viscosity, which promotes vaso-occlusion

and thrombotic phenomena” (Adekile, 2013). Developing the appropriate plan of care for an

individual suffering from sickle cell can be difficult, robust “recommendations for children and

adults with proliferative sickle cell retinopathy include referral to an expert specialist for

consideration of laser photoagulation and for echocardiography to evaluate signs of pulmonary

hypertension” (Yawn et al., 2014). Individuals exemplifying complications from sickle cell

should be addressed with, “rapid Bone marrow transplants is effective however, there are a

minimum amount on the transplant registry” (Yawn et al., 2014). Providers should prescribe

hydroxyurea more frequently as it will decrease a number of sickled cells, therefore, decreasing

crisis episodes decreasing pain and complications.

Complications

There are multiple complications associated with sickle cell disease. Anemia is the most

common as the sickle shape RBCs:

break apart easily and die, leaving you without enough red blood cells. Red blood cells

usually live for about 120 days before they need to be replaced. But sickle cells usually

die in 10 to 20 days, leaving a shortage of red blood cells ("Symptoms and Causes",

2016).
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Patients suffering from anemia will also experience fatigue. As the sickle shape cells impede,

blood flow patients may experience swelling of dependent extremities and retina damage. As

sickle cell disease causes inadequate oxygenation and the bodies need for oxygen and nutrients

to promote growth sickle cell patients could potentially experience delayed growth. During the

crisis phase patients, will experience extreme episodes of pain in various parts of the body such

as bones, joints, chest, and abdomen. The intensity of pain varies as well as the longevity of the

painful episodes can last a few hours or a few days ("Symptoms and Causes", 2016).

Conclusion

Developing and implementing robust educational programs for sickle cell disease will

create awareness, “the most cost-effective strategy for reducing the burden of hemoglobin

disorders is to complement disease management with prevention programs” ("Sickle-cell disease

and other hemoglobin disorders", 2011). Therefore, individuals suffering from sickle cell disease

will have better outcomes because the disease process will be appropriately managed.

Individuals with sickle cell disease should have their pain managed appropriately during the

crisis phase and received adequate oxygenation to decrease the chance of ischemic episodes.

Supporting sickle cell research will foster an improved standard of care leading to increasing

longevity and a restored quality of life for sickle cell patients.

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References

Adekile, A. (2013). What's new in the pathophysiology of sickle cell disease?. Medical

Principles and Practice, 22(4), 311-312. http://dx.doi.org/10.1159/000350283

Bandeira, I., Rocha, L., Barbosa, M., Elias, D., Querioz, J., Freitas, M., & Gonçalves, R. (2014).

Chronic inflammatory state in sickle cell anemia patients is associated with HBB*S

haplotype. Cytokine, 65(2), 217-221. http://dx.doi.org/10.1016/j.cyto.2013.10.009

“Complications and treatments”. (2016). CDC. Retrieved from

https://www.cdc.gov/ncbddd/sicklecell/treatments.html

Gould, B. & Dyer, R. (2011). Pathophysiology for the health professions (1st ed.). St. Louis, Mo:

Saunders Elsevier.

Hounkpe, B., Fiusa, M., Colella, M., Nilkenes Gomes da Costa, L., Benatti, R., & Olalla Saad, S.

(2015). Role of innate immunity-triggered pathways in the pathogenesis of sickle cell

disease: A meta-analysis of gene expression studies. Scientific Reports, 5, 17822.

http://dx.doi.org/10.1038/srep17822

Labie, D. & Elion, J. (1999). Molecular and cellular pathophysiology of sickle cell anemia.

PubMed. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10081773

Loiselle, K., Lee, J., Szulczewski, L., Drake, S., Crosby, L., & Pai, A. (2015). Systematic and

meta-analytic Review: Medication adherence among pediatric patients with sickle cell

disease. Journal of Pediatric Psychology, 41(4), 406-418.

http://dx.doi.org/10.1093/jpepsy/jsv084

Moscou-Jackson, G., Allen, J., Kozachik, S., Smith, M., Budhathoki, C., & Haywood, C. (2016).

Acute pain and depressive symptoms: Independent predictors of insomnia symptoms

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among adults with sickle cell disease. Pain Management Nursing, 17(1), 38-46.

http://dx.doi.org/10.1016/j.pmn.2015.09.002

Sickle-cell disease and other hemoglobin disorders. (2011). World Health Organization.

Retrieved from http://www.who.int/mediacentre/factsheets/fs308/en/

Skidmore-Roth, L. (2015). Mosby's drug guide for nursing students. St. Louis: Elsevier Mosby.

Stettler, N., McKiernan, C., Melin, C., Adejoro, O., & Walczak, N. (2015). Proportion of adults

with sickle cell anemia and pain crises receiving hydroxyurea. JAMA, 313(16), 1671.

http://dx.doi.org/10.1001/jama.2015.3075

Strouse, J. (2016). Cerebral oxygenation and transfusion for severe anemia. JAMA Pediatrics,

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“Symptoms and causes” (2016). Mayo Clinic. Retrieved from

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20303269

Yawn, B., Buchanan, G., Afenyi-Annan, A., Ballas, S., Hassell, K., & James, A. (2014).

Management of sickle cell disease. JAMA, 312(10), 1033.

http://dx.doi.org/10.1001/jama.2014.10517