Sickle Cell Anemia: a Case Study

Case Study

A 19-year-old African-American female, hereafter referred to as “AP”, presents to her primary care physician with fatigue, fever, and right upper quadrant (RUQ) abdominal pain for 3 days. AP has a significant medical history of sickle cell anemia (SCA). AP also complains of generalized “bone-crushing” pain rated 10/10 intermittently, with notable swelling to bilateral hands and feet. Sickle cell disease (SCD) affects an estimated 70,000 to 100,000 Americans. One to three million Americans are estimated to be carriers of the sickle cell trait. This disease is usually diagnosed in early childhood and associated symptoms can be debilitating. The purpose of this paper is to discuss SCA in general, and as it pertains to the above case study.

Pathophysiology

Sickle cell disease is an autosomal recessive disorder located on chromosome 11p15.5 affecting the functioning of red blood cells. Worldwide, sickle cell affects millions of lives and is most often seen in people with ancestors from Africa, although individuals with backgrounds from Mediterranean countries, Arabian Peninsula, South America, Central America, and the Caribbean may also be affected. Sickle cell disease is an umbrella term for individuals who express an abnormal gene that causes the body to make hemoglobin (Hb) S. The different types of SCD are Hb SβO thalassemia, Hb Sβ+ thalassemia, HbSC, HbSD, HbSE, and HbSS (NHLBI, n.d.). AP has HbSS which is the most common and most severe form of SCD. Other types of SCD are not as common. AP inherited one abnormal Hb gene from each parent in order to have SCD (NHLBI, n.d.). AP’s parents may have either had SCD themselves or sickle cell trait to pass it on to their children. Individuals with sickle cell trait may not know they have it unless it is tested through newborn screening or their parents are aware of their own status. Individuals with sickle cell trait are rarely symptomatic due to other types of Hb in the cell.

Sickle cell disease is characterized by the irregular shape of Hb, causing rigidity in red blood cells and “C” or sickle-shaped red blood cells. The sickle shape of the red blood cells is due to Hb S being less soluble when deoxygenated which causes it to precipitate and polymerize at a faster rate. Oxygen is moved throughout the body with the assistance of Hb, a protein found in healthy red blood cells (ASH, 2018). Injury to the red blood cell causes hemolytic anemia, microvascular occlusions, derangement and tissue damage which may lead to organ failure. Hemoglobin S polymerization, impaired blood flow caused by vascular occlusion, hemolysis-mediated endothelial dysfunction, and activation of sterile inflammation are four major developments involved in a vicious cycle that makeup SCD.

Individuals with SCD and sickle cell trait are found to have resistance to falciparum malaria and exhibit lower parasite counts (Serjeant, 2013). Although there are different theories as to why individuals with sickle cell trait are found to have a resistance to malaria, one theory states that when an individual is infected with malaria, the abnormal Hb tends to sickle with the malaria parasite and is then subsequently removed by macrophages. AP has not travelled out of the country recently, and therefore malaria is not included in the differential diagnosis.

Manifestations and Diagnosis

AP is referred to the emergency room to be evaluated for sickle cell crisis and possible cholecystitis.

Physical Exam

AP appears to be in severe distress. AP describes her pain as intermittent generalized pain but worsened in her arms, feet and RUQ of the abdomen. AP reports she is currently going through major stress at school. AP states that this feels like “a crisis” but her abdomen doesn’t usually hurt “this bad” and is now experiencing nausea. AP states pain has been going on for 3 days and is worse after she eats. AP has brought a copy of her medical records with her. It is noted that she has the genotype HbSS, also known as SCA. Hands and feet are noted to be swollen, and AP reports “pain worsens with joint movement.” In addition, lower extremity ulcerations are noted, which may be a chronic manifestation of sickle cell disease (Linder & McCance, 2019). Initial vital signs for AP are: pulse 115 bpm, respirations 24, blood pressure 120/79, temperature 100.9, pulse ox 96% on room air.

On exam, her abdomen is mildly distended and tender to palpation on the RUQ with a positive Murphy sign. Since acute chest syndrome (ACS) can be a life-threatening complication seen in vaso-occlusive crisis, it is important to evaluate the patient and recognize the most common signs and symptoms associated with this condition such as cough, hemoptysis, shortness of breath, chest pain, low oxygen saturation, wheezing or other abnormal lung sounds. Acute chest syndrome is the number one cause of premature death in patients with SCD, therefore thorough examination is needed when patients present with fever, hypoxia or new onset infiltrate in chest x-ray. An acute drop of Hg in patients with SCD may indicate worsening disease or the presence of other complications such as ACS, hepatic or splenic sequestrations (Simon et al., 2016). In this case, AP does not appear to have labored breathing, her oxygen saturation is normal, lung sounds are clear bilaterally and she denies any cough, shortness of breath, or radiating pain to her chest. AP also denies any previous history of ACS. However, further testing is needed to rule out ACS. The differential diagnosis for AP is: vaso-occlusive crisis, acute chest syndrome, infection due to impaired splenic function, cholecystitis, acute sickle hepatic crisis.

Lab Work and Diagnostics

A CBC, liver function panel, coagulation studies, type and screen, a chest x-ray, RUQ ultrasound (US) and continuous oxygen monitoring are indicated. Leukocytosis with a left shift is noted. Hemoglobin is 6.5g/dL and hematocrit is 25%, which are consistent with previous lab values during crisis for AP according to her medical records. Liver function, coagulation studies and chest x-ray are within normal limits. Oxygen saturation on room air continues to be >95%. Right upper quadrant ultrasound shows gallbladder wall thickening and pericholecystic fluid.

Since abdominal pain is common in patients with SCD, it is important to identify the cause. In this case, pain is localized to the RUQ, therefore diagnostic tests are needed to differentiate between cholecystitis, cholelithiasis, or acute sickle hepatic crisis. Clinical presentation of acute cholecystitis includes RUQ pain, fever, nausea and vomiting, laboratory and imaging studies may show elevated white count, elevated transaminase, gallbladder wall thickening, pericholecystic fluid, or dilation of the common bile duct (Simon et al., 2016). Acute sickle hepatic crisis tends to have similar presentation as cholecystitis, however hepatomegaly is seen in acute sickle hepatic crisis. In addition, it is recommended to obtain previous laboratory analyses in order to establish a baseline of a patient’s Hb levels and liver function and thus identify acute processes. In the present case study, AP was diagnosed with vaso-occlusive crisis complicated with cholecystitis.

Treatment

AP was then admitted to the hospital for treatment of vaso-occlusive crisis and cholecystitis. Due to the crisis and the high probability of impending surgery, treatment of the patient would include a blood transfusion. A blood transfusion would contain normal Hb, which would then survive longer in the circulatory system decreasing blockage risk and increasing oxygen supply to tissues (NHLBI, n.d.). Prior to surgery, patients with sickle cell anemia can receive blood transfusions to prevent further complications post-operatively.

Medication management would be initiated for AP to prevent further sickling and complications of tissue damage. With episodes of severe pain, interventions would include pain management, hydration, and possibly the use of anti-inflammatory agents. Frequent pain assessments and management would be needed for AP. A multidisciplinary approach would be appropriate for pain management. Often, patients out of the hospital treat their pain with ibuprofen or aspirin found over the counter, but due to the severity of AP’s pain an opioid analgesic will be needed. The medication hydroxyurea is an example of a home medication used to prevent crisis in SCD patients. Hydroxyurea stimulates fetal Hb to be produced which prevents the production of sickle cells. AP does not take hydroxyurea as a home medication. AP states she “stopped taking it a year ago because she would forget to take it due to stress of school.”

Since AP presented with the complicating signs of cholecystitis, an operation may be needed. The most standard procedure would be a laparoscopic cholecystectomy. The use of prophylactic antibiotics for AP would be needed because patients with SCD are more susceptible to infection due to either abnormal or absent function of the spleen. Broad spectrum antibiotics, such as cephalosporins alone or in combination with gentamicin, may be a treatment option for AP. During AP’s cholecystectomy, special intraoperative care needs to be provided to keep AP warm and prevent further occlusion. A thermal cover may be used in order to keep the patient warm. Post-operatively AP would need oxygen therapy, adequate pain control, and fluids may need to be continued for up to 1-2 days. Frequent assessments and lab monitoring would be needed to evaluate for signs and symptoms of infection and further complications.

Complications

Sickle cell disease, or sickle cell anemia, can increase risk of complications including: stroke, pulmonary hypertension, organ damage, blindness, vascular damage, gallstones, etc. For the purposes of this case study, AP will need to be monitored specifically for pulmonary, vascular, and neurological complications. Pulmonary complications include acute chest syndrome and pulmonary hypertension. Acute chest syndrome is the second most common reason for hospitalization of sickle cell patients. Due to the sickling of the red blood cells, occlusions will occur in organ systems, including the lungs, and this damage leads to increased pressure in the lungs. Pulmonary hypertension affects around 10% of adults with SCD, specifically pulmonary arterial hypertension. Vascular complications related to hemolysis in SCD can include ulcers in the legs and priapism (Dubert et al., 2016). Complications related to low Hb levels in SCD include albuminuria and leg ulcers (Dubert et al., 2016). As previously stated, sickling of the red blood cells can cause clumping in the vessels and lead to vascular occlusion, leading to further complications.

Neurological complications can occur in SCD because sickled cells can damage vessels when they cluster together. Risk of stroke is the most severe of these neurological complications. It has been shown that infarctions and brain atrophy are seen in SCD patients, children included, and that this can result in cognitive decline (Venkataraman & Adams, 2014). Prevention includes screening by age 2 and if deemed high risk, giving regular blood transfusions. Prevention in adults is not yet developed. AP has eluded any major complications. AP tolerated the surgery and blood transfusions well, and has recovered over 2 days on a Med-Surg unit. Her pain has decreased to a 5/10 generalized, and is managed with anti-inflammatory medications. AP remains afebrile and is tolerating soft foods well without any complaints of nausea. AP is now ready for discharge planning, which includes discharge instructions and education.

Education

Education for AP will focus on post-cholecystectomy instructions, future infection prevention, and stress and health management with SCD. The Centers for Disease Control and Prevention website (CDC, 2018a) has several educational handouts for patients with SCD and could be utilized as a free online resource. Post-cholecystectomy, AP will need to follow a specific diet to decrease risk of diarrhea or other gastrointestinal (GI) symptoms. To decrease risk of GI symptoms, AP should be encouraged to eat a low-fat diet for at least one-week post-op. Patients with a history of SCD should be encouraged to drink 8-10 glasses of water daily. This would also help prevent dehydration if AP experiences diarrhea. To help prevent infection, AP is instructed to wash her hands frequently, especially before preparing or eating food and after going to the bathroom (CDC, 2018c). AP is educated that use of hand sanitizer is acceptable, but that hand washing to prevent pathogen transmission is best practice. AP would be instructed to continue taking any prescribed antibiotics until they are gone, to monitor the surgical incision sites for inflammation or drainage, and to immediately report any signs of infection to their physician. If a patient experiences any future complications with SCD, such as sudden uncontrolled pain, chest pain, severe headache, or vision problems they should seek medical attention. To help prevent future SCD crisis, stress and health management should be a priority. As a college student, AP previously stated she was “going through major stress at school.” To specifically manage stress, some interventions can include: scheduling times to rest during daily activities when possible, creating an on-campus support network of people who are aware that AP has SCD and can be supportive if she is overwhelmed, establishing a working relationship with an academic advisor to advocate for AP in the event of an emergency, and joining a support group with other college students with SCD (CDC, 2018e). AP was already practicing some of the recommendations to increase quality of life with SCD, by seeking medical attention when having symptoms and carrying a copy of her medical record with her. Other considerations AP would be encouraged to do is to stay active with exercise that will not make AP too hot or cold or fatigued, eat a healthy diet with plenty of fruits and vegetables, increase water intake, and to consistently follow up with her primary care physician or hematologist to manage SCA.

Conclusion

In summary, AP was evaluated and treated for vaso-occlusive crisis and cholecystitis related to her history of SCA. She tolerated pain management, IV hydration and surgical treatment well, and was discharged from the hospital. At follow up with her hematologist, AP states she finished her antibiotics, has had less loose stools recently, and denies abdominal pain. AP denies fever or signs of infection, and states she has been trying to drink plenty of water. AP states her pain is controlled at home with anti-inflammatory medications. AP has reorganized some of her school schedule and will finish the semester successfully with her stress better managed. AP states she will consider restarting her prescribed hydroxyurea, which is encouraged by her hematologist. Sickle cell disease can be a painful and debilitating, but with proper management of symptoms a patient can have the possibility to live a full life.

References

1. Al Talhi, Y., Shirah, B. H., Altowairqi, M., & Yousef, Y. (2017). Laparoscopic cholecystectomy for cholelithiasis in children with sickle cell disease. Clinical Journal of Gastroenterology, 10(4), 320-326. doi:10.1007/s12328-017-0750-3
2. American Society of Hematology [ASH]. (2018). Sickle cell disease [Website]. Retrieved from https://www.hematology.org/Patients/Anemia/Sickle-Cell.aspx
3. Bender, M. A. (2017). Sickle cell disease. Retrieved from https://www.ncbi.nlm.nih.gov/sites/books/NBK1377/
4. Centers for Disease Control and Prevention [CDC]. (2017). Complications and treatments of sickle cell disease [Website]. Retrieved from https://www.cdc.gov/ncbddd/sicklecell/treatments.html#Pain
5. Centers for Disease Control and Prevention [CDC]. (2018a). Sickle cell disease (SCD) [Website]. Retrieved from https://www.cdc.gov/ncbddd/sicklecell/materials/factsheets.html
6. Centers for Disease Control and Prevention [CDC]. (2018b). Living well with sickle cell disease [PDF Document]. Retrieved from https://www.cdc.gov/ncbddd/sicklecell/documents/tipsheets_living.pdf
7. Centers for Disease Control and Prevention [CDC]. (2018c). 5 Tips to help prevent infection [PDF Document]. Retrieved from https://www.cdc.gov/ncbddd/sicklecell/documents/tipsheets_5.pdf
8. Centers for Disease Control and Prevention [CDC]. (2018d). Emergency Guide: When to see the doctor [PDF Document]. Retrieved from https://www.cdc.gov/ncbddd/sicklecell/documents/tipsheets_guide.pdf
9. Centers for Disease Control and Prevention [CDC]. (2018e). 9 Tips to living well with SCD in college [PDF Document]. Retrieved from https://www.cdc.gov/ncbddd/sicklecell/documents/SCD-factsheet_9steps.pdf
10. Dubert, M., Elion, J., Tolo, A., Diallo, D. A., Diop, S., Diagne, I., … & Ranque, B. (2016). Degree of anemia, indirect markers of hemolysis and vascular complications of sickle cell disease in Africa. The American Society of Hematology, 130, 2215-2223. doi:10.1182/blood-2016-12-755777
11. Ghosh, S., Adisa, O., Chappa, P., Tan, F., Jackson, K., Archer, D. R., & Ofori-Acquah, S. F. (2013). Extracellular hemin crisis triggers acute chest syndrome in sickle mice. Journal of Clinical Investigation, 123(11), 4809-4820. doi:10.1172/JCI64578
12. Gordeuk, V., Castro, O. & Machado, R.F. (2016). Pathophysiology and treatment of pulmonary hypertension in sickle cell disease. Blood, 127, 820-828. doi:10.1182/blood-2015-08-618561
13. Howard, J., Hart, N., Roberts‐Harewood, M., Cummins, M., Awogbade, M., Davis, B., . . . the BCSH Committee. (2015). Guideline on the management of acute chest syndrome in sickle cell disease. British Journal of Haematology, 169(4), 492-505. doi:10.1111/bjh.13348
14. Linder, L. A. & McCance, K. L. (2019). Alterations of hematologic function in children. In K. L. McCance & S. E. Huether (Eds.), Pathophysiology: The biologic basis for disease in adults and children (8th ed.) (pp. 992-1016). St. Louis, MO: ELSEVIER.
15. Luzzatto, L. (2012). Sickle cell anemia and malaria. Mediterranean Journal of Hematology and Infectious Diseases, 4(1). doi:10.4084/mjhid.2012.065
16. Mayo Clinic. (2018). Sickle cell anemia [Website]. Retrieved from https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/symptoms-causes/syc-20355876
17. National Heart, Lung, and Blood Institute [NHLBI]. (n.d.). Sickle cell disease [Website]. Retrieved from https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease
18. Oneal, P.A., Schechter, G.P., Rodgers, G.P., & Miller J.L. (2019). Hemolytic Anemia. In Rodgers G.P.The Bethesda handbook of Clinical Hematology. Philadelphia, PA: Wolters Kluwer.
19. Serjeant, G. R. (2013). The Natural History of Sickle Cell Disease. Cold Spring Harbor Perspectives in Medicine, 3(10). doi:10.1101/cshperspect.a011783
20. Simon, E. Long, B. & Koyfman, A. (2016). Emergency medicine management of sickle cell disease complications: An evidence-based update. Journal of Emergency Medicine, 51(4), 370-381. doi:10.1016/j.jemermed.2016.05.042
21. Sundd, P., Gladwin, M. T., & Novelli, E. M. (2019). Pathophysiology of Sickle Cell Disease. Annual Review of Pathology: Mechanisms of Disease, 14(1), 263-292. doi:10.1146/annurev-pathmechdis-012418-012838
22. Venkataraman, A. & Adams, RJ. (2014). Neurologic complications of sickle cell disease. Handbook of Clinical Neurology, 120, 1015-1025. doi:10.1016/B978-0-7020-4087-0.00068-1
23. Yueh, T., Chen, F., Lin, T., & Chuang, M. (2014). Diarrhea after laparoscopic cholecystectomy: Associated factors and predictors. Asian Journal of Surgery, 37(4), 171-177. doi:10.1016/j.asjsur.2014.01.008