Maedbh Lillis

CHEM 349

Case Study #5 Report - Sickle Cell Anemia

ABSTRACT

This paper explores the biochemical processes driving sickle cell anemia and the medical, ethical

and public health implications of a the sickle cell trait. Due to improvements in medical

technology, sickle cell anemia is now viewed as manageable condition that does not preclude a

person from leading a relatively normal life. Research has shown that taking prescribed opioid

medications and regularly consulting a with medical professional prevent the occurrence of acute

and life-threatening compilations such as stroke and acute respiratory syndrome.

INTRODUCTION

Sickle cell anemia is one of the most common monogenic blood disorders in the world,

with approximately 100,000 Americans living with the disease. Sickle cell disease is caused by a

mutation in the hemoglobin-beta (HBB) gene located on chromosome 11. Normal Red blood

cells with hemoglobin-alpha (HBA) are round and smooth with the ability to flow through blood

vessels easily and transport oxygen throughout the body. People with sickle cell disease have

abnormal hemoglobin molecules shaped like long rods, which causes the erythrocytes to stiffen

and take on a sickle shape. The irregular shape of the red blood cells causes them to pile up in

the vessels, creating blockages and damaging tissues and organs (Samuel, 1997).

The sickle cell trait is inherited when a person receives a copy of the sickle cell trait from

each parent. A person who only inherits one copy of the altered gene is known as a carrier and

usually does not show clinical symptoms of the disease. There are approximately 2.5 million
sickle cell trait carriers in the United States (American Society of Hematology, 2017). Sickle cell

disease destroys erythrocytes at a rapid rate, and patients suffer from chronic anemia (low

hemoglobin levels). Left untreated, sickle cell disease can cause chronic pain and life-threatening

complications secondary to major organ damage (American Society of Hematology, 2017).

What research is being done to better understand the sickle cell trait?

Sickle cell disease has a highly variable clinical presentation - some patients live

relatively normal lives with mild symptoms while others suffer from markedly shorter lifespans

due to severe complications (American Society of Hematology, 2017). Research suggests that a

persons genetic information alone cannot predict the severity or course of their illness.

CASE STUDY

In the original case report, the patient was a 25 year old African American male with

sickle cell anemia who had a history of vaso-occlusive crises. A vaso-occlusive crisis is a

painful complication of sickle cell anemia where the sickled erythrocytes obstruct the circulation

of blood vessels, causing ischemic (circulatory) issues. The patient reported good health for the

past several years and was prescribed oral analgesic for pain. He was admitted to the emergency

room after 4-5 days of back and flank pain that had gradually increased in severity. The patient

was afebrile and was treated with IV fluids and analgesics. His serum bilirubin value was 5.1

mg/dl (normal range is 0.3-1.2 mg/dl), the white blood cell was count 18,000/mm^3

(2,400-10,800/mm^3 is the normal range), and the hematocrit (the ratio of RBC volume to total

blood volume) was 37% (37.2-50.2% is the norm) (Samuel, 1997).

After being discharged with an oxymorphone prescription, the patient returned to the

emergency room a few days later complaining of severe generalized pain, fever, and sweats. He
was found to have pleuritic chest pain and mild dyspnea along with a temperature of 100.9F and

jaundice. The physical exam revealed rales (rattling sounds) heard in lungs upon auscultation and

The leukocyte count had risen to 26,000/mm3 with a serum bilirubin of 9.1 mg/dl. The chest

x-ray displayed showed a slightly enlarged heart with fluid in the right minor fissure in the lung,

which are findings consistent with pleural effusion. The electrocardiogram showed sinus

tachycardia with left ventricular enlargement.

The patients blood, throat, and urine cultures were collected for further lab analysis.

Initial treatment included cefotaxime (an antibiotic), meperidine (a narcotic analgesic), and 40

percent oxygen by facemask (Samuel, 1997). Within twelve hours, the patients fever had risen

to 102.7F and he had become tachypneic with a respiratory rate of 40 breaths per minute. An

arterial blood gas sample showed a PO2 (partial pressure of oxygen) of 41 torr (>79 torr is

normal) despite the supplemental oxygen administration, which was then increased to 100%. The

patient was transferred to the intensive care unit while the lab results came through.

Gram stains of the pleural fluid and sputum was negative for Legionella organisms.

Pneumonia could not be completely ruled out at this stage, so the antibiotics were switched to

ampicillin, gentamicin, and trimethoprim-sulfamethoxazole. The patients condition continued to

worsen over the next several days, with a constant fever and a leukocyte count that had now risen

to 46,000/mm^3. An endotracheal tube was inserted after four days when the partial pressure of

oxygen would not rise above 50 torr. The patient was given an exchange transfusion of 5 units of

packed erythrocytes, which raised his hemoglobin to 70%. Throughout his hospital stay, the

patient received transfusions as necessary to maintain his hematocrit above 70% (Samuel, 1997).
 After nine days in the ICU, the patients temperature returned to normal and his

endotracheal tube was removed after taking him off the ventilator. Lab cultures failed to provide

any evidence of an infectious cause of illness. The antibiotics were discontinued and he was

transferred to a general medical ward for another nine days for furthering monitoring. The

patient spent a total of 22 days in the hospital and the x-ray taken on day of discharge showed no

effusions. The discharge diagnosis was adult respiratory distress syndrome complicating sickle

cell vaso occlusive crisis.

DIAGNOSIS OF SICKLE CELL DISEASE

A routine blood test can be given to check for hemoglobin S, which is usually done in an

initial screening of a newborn at a hospital. In adults, a diagnosis is made by electrophoretic

analysis of lysed red blood cells drawn from the arm. The sickle cell mutation causes the

hemoglobin tetramer to lose two negative charges at pH 8.6 because the glutamic acid side chain

is negatively charged in this environment (Samuel, 1997). Consequently, the hemoglobin A

moves more rapidly towards the positive anode than hemoglobin S at pH 8.6 on cellulose

acetate.

BIOCHEMICAL PATHWAYS OF SCA

A vaso occlusive crisis is one of the hallmark symptoms of sickle cell disease that can be

triggered by dehydration, fever, hypothermia, or stress. Activated mast cells release neuropeptide

substance P and other mediators in the skin to sensitize peripheral pain receptors. Pain signals

travel from the periphery through the spinal cord to the brain. Sustained sensitization leads to

antidromic release of neuropeptides and pain mediators in the periphery, which causes pain to be
felt without a harmful stimulus (Aich, 2016). The result is a cyclic feed-forward pathway of

peripheral and CNS sensitization that accounts for the chronic pain found in sickle cell patients.

TREATMENT

Vasoocclusive crises are treated with hydration and analgesics. Pain control is best

achieved with opioids and opiate derivatives. Infection prevention also aids a patients chances

of survival, which explains the use of antibiotics in the case study. An allogeneic bone marrow

transplant can help a sickle cell patients body produce normal hemoglobin - the benefits may

outweigh the risks if the patients condition is severe. The case study patients worsening

condition in the ICU may have warranted a bone marrow transplant if his condition had

continued to deteriorate.
PATIENT OUTCOMES

Sickle cell patients can live normal lives - average life expectancies currently average

about 60 years for men and 68 for women. As with all people, a healthy diet, regular physical

activity, and good sleeping habits will improve quality of life. People with sickle cell disease are

prone to tiring more quickly than usual, so they must take care to avoid overexertion and

excessive stress. Circumstances that may trigger a vasoocclusive crisis include extreme heat or

cold, dehydration, and unpressurized cabins in airplanes. (American Society of Hematology.

2017). Taking medications as prescribed and keeping regular doctor appointments decrease the

incidence of acute problems.

SCREENING AND ETHICAL CONCERNS

Infants can be screened for sickle cell disease before they are born via amniocentesis. The

decision to terminate a pregnancy depends on a variety of personal and cultural considerations as

well have the health of the mother. Outcome for people living with sickle cell disease are

exponentially better than they they were 40-50 years ago, but one must consider the impact of

limited healthcare resources in the third world country. In a country such as Nigeria, scarcity of

resources and health care rationing may be more readily apparent. Parents may find themselves

in the position to decide if they could live with the consequences of a suffering child who may

not be able to get adequate treatment.

In developed countries, a procedure called preimplantation genetic diagnosis is intended

to prevent certain genetic disorder by identifying and eliminating embryos with genetic defects.

This practice is filled with its own moral pitfalls related to the destruction of embryos and the

eugenicist policies for the best genetic traits.

 The patient in the case study was treated according to the standard of care for a vaso

occlusive crisis. The incident appeared to be a recurring flare-up of a condition that had affected

him since childhood. The medical team could not have done anything differently other than

giving him a bone marrow transplant if appropriate and viable. The medical staff could have also

evaluated the patient's lifestyle and counseled him on healthy habits to improve- his quality of

life.

DISCUSSION

Sickle cell anemia is increasingly being viewed as a chronic condition that can be

managed with appropriate medication and lifestyle adjustments. The medical team left no stone

unturned in the diagnostic process, taking lab cultures to determine if pneumonia could be a

cause of the patient's pain and respiratory distress. Antibiotics were given as curative measure

against further complications when pneumonia could not be ruled out. The patients condition

worsened before slowly moving after after a stint in the intensive care unit that included IV

fluids, intubation, antibiotics, and pain medications. The cyclic feed-forward pain pathway that

causes suffering the sickle cell patients can be appropriately managed with medication and

hydration.

 References

American Society of Hematology. (2017). Sickle Cell Research Priorities. American Society

of Hematology, Retrieved From

http://www.hematology.org/Research/Recommendations/Sickle-Cell/3151.aspx

Anupam Aich, Alvin J Beitz and Kalpna Gupta (2016). Mechanisms of Pain in Sickle Cell

Disease, Sickle Cell Disease - Pain and Common Chronic Complications, Dr. Baba P.D. Inusa

(Ed.), InTech, DOI: 10.5772/64647. Available from:

https://www.intechopen.com/books/sickle-cell-disease-pain-and-common-chronic-complications

/mechanisms-of-pain-in-sickle-cell-disease

Samuel Charache. (1997). Sickle Cell Anemia. Clinical Studies in Medical Biochemistry. New

York: Oxford university Press. 78-90

Outline:

1. Intro- sickle cells

a. One of the most common monogenic blood disorders in the world

i. People with sickle cell disease have abnormal hemoglobin molecules

shaped like long rods

1. Causes the erythrocytes to stiffen and take on a sickle shape

2. Red blood cells causes them to pile up in the vessels, creating

blockages

ii. The irregular shape of the red blood cells causes a pile up in the vessels

1. This leads to blockages damaging tissues and organs.

b. The sickle cell trait is inherited when a person receives a copy of the sickle cell

trait from each parent

i. A carrier usually does not show clinical symptoms of the disease.

1. They destroy erythrocytes at a rapid rate that make patients suffer

from chronic anemia

ii. Anything left untreated, can cause chronic pain and life-threatening

complications

c. Sickle cell disease can cause chronic pain and life-threatening complications

d. Some patients live relatively normal lives with mild symptoms while others suffer

from markedly shorter lifespans

2. Vaso-occlusive crisis is a painful complication of sickle cell anemia

i. The sickled erythrocytes obstruct the circulation of blood vessels, causing

ischemic (circulatory) issue

ii. Patient example- treatable with IV fluids and analgesics

1. Treatment may revealed pleuritic chest pain and mild dyspnea

along with high body temperature jaundice.

2. Physical exam on patient revealed rales (rattling sounds) heard in

lungs upon auscultation

b. Patient experienced a slightly enlarged heart with fluid in the right minor fissure

in the lung

1. Resulted in findings consistent with pleural effusion

c. Patients blood, throat, and urine cultures were collected for further lab analysis.

i. Intensive care unit

ii. Initial treatment for symptom included antibiotics, and narcotic analgesic,

and 40 percent oxygen by facemask

3. Routine blood test can be given to check for hemoglobin S,

a. sickle cell mutation causes the hemoglobin tetramer to lose two negative charge

4. Vaso occlusive crisis is one of the hallmark symptoms of sickle cell disease that can be

triggered by dehydration, fever, hypothermia, or stress

a. Present schematic of this biochemical pathway what particular pathway is

affected in

b. Pain signals travel from the periphery through the spinal cord to the brain.
5. How patient condition fits into this larger biochemical pathway what particular part is

affected

6. Vasoocclusive crises are treated with hydration and analgesics.

a. Pain control

i. Achieved with opioids and opiate derivatives

b. Infection prevention also aids a patients chances of survival

i. Use of antibiotics.

c. An allogeneic bone marrow transplant can help a sickle cell patients body

produce normal hemoglobin

i. Benefits may outweigh the risks if the patients condition is severe

d. Average life expectancies currently average about 60 years for men and 68 for

women

i. A regular healthy lifestyle is beneficial to the patient

ii. Prone to tiring more quickly than usual

1. Overexertion and excessive stress is likely to be avoided

2. Must avoid extreme heat or cold, dehydration, and unpressurized

cabins in airplanes.

7. Infants can be screened for sickle cell disease before they are born via amniocentesis

a. Outcome for people living with sickle cell disease are exponentially better than

they they were 40-50 years ago

b. Take into effect the impact of limited healthcare resources in some countries
 i. Scarcity of resources and health care rationing may be more readily

apparent

ii. Preimplantation genetic diagnosis can identify and eliminate embryos with

genetic defects

8. Patient in the case study was treated according to the standard of care for a vaso occlusive

crisis

a. Medical team could not have done anything differently other than giving him a

bone marrow transplant if appropriate and viable

9. Sickle cell anemia is increasingly being viewed as a chronic condition that can be

managed with appropriate medication and lifestyle adjustments

a. medical team left no stone unturned in the diagnostic process

i. Taking lab cultures to determine if pneumonia could be a cause of the

patient's pain and respiratory distress.

ii. Antibiotics were given as curative measure against further complications

iii. The patients condition worsened before slowly moving after after a stint

in the intensive care unit that included IV fluids intubation, antibiotics,

and pain medications.