What is Sickle Cell Disease

Figure 1: Sickle Cell Disease. 

What is Sickle Cell Disease?^1,2,3
Sickle cell disease (SCD) is part of a group of disorders called sickle cell syndromes, which are characterized by a defect in the red blood cells (RBCs) that produces an abnormal sickle cell hemoglobin (HbS). There are many types of SCD including HcSC, HbSβ⁺-thal, and HbSβ⁰-thal, but the most common type is HbSS. The sickle cell trait (SCT) is caused by inheritance of one normal hemoglobin gene and one abnormal HbS gene, and carriers of the SCT do not have any signs of the disease.

The defective hemoglobin in SCD induces a “sickling” of the shape of RBCs, which causes cells to clump together or aggregate within small blood vessels, as seen in Figure 1. This causes blood flow to be blocked, also known as vaso-occlusion, and leads to acute painful episodes and irreversible damage to many organs. SCD is a chronic, lifelong condition that has a significant burden on patients and their families, so it is important for those with SCD to become aware of the potentially life-threatening complications of this disease.

Who is affected by SCD?^1,4

Figure 2: Inheritance of Sickle Cell Anemia.

This disease most commonly affects African Americans or those of African descent. This is due to the possibility of the SCT having developed as a protective factor against malarial infection in these areas of the world where malaria is endemic.

SCD is an inherited genetic disease, and Figure 2 depicts the chances of inheriting SCD for a child born to parents who both carry the SCT.  If both parents carry the SCT and physician concern is high for the potential of SCD in the unborn child, prenatal testing can be done safely and accurately at the end of the first trimester.

Other interesting statistics:

●      About 90,000 Americans are currently living with SCD

●     In the United States about 1 in 500 African Americans and 1 in 36,000 Hispanic Americans are born with SCD

●      About 2 million Americans have SCT

●      1 in 12 African Americans are born with SCT

The introduction of the pneumococcal vaccine in 2000 helped reduce the risk of pneumonia, a common complication of SCD.  The SCD mortality rates in African American children decreased by 42% from 1999 to 2002, due to the increased protection from this invasive infection.

How is SCD diagnosed?^1,3

Prenatal testing for SCD is not necessary in most cases, so SCD is usually identified by routine infant screening tests. Typically screening is performed by a simple blood test that is sent to an outside laboratory for processing. In the United States newborn screenings for sickle cell hemoglobin is required by most states, and this early diagnosis has allowed for timely comprehensive care in newborns who test positive for SCD.

What are the sign, symptoms, and complications associated with SCD?^1,3,5

v  Anemia: Patients with SCD have hemoglobin levels often ranging from 6 to 9 g/dL, well below the normal range of 13 to 15 g/dL. These patients will also have elevated levels of immature RBCs. RBCs undergo accelerated destruction with lifespans ranging from as little as 10 to 15 days, compared to the usual lifespan of 120 days. Patients with less severe forms of SCD will have lower rates of RBC destruction, and patients with infections may experience decreased hemoglobin levels due to suppression of the production of RBCs.

v  Vaso-occlusion: This is the most common and painful complication of SCD and is a major cause of morbidity and mortality associated with the disease. Vaso-occlusion is a result of the sickled RBC aggregation that can cause damage in many areas. Loss of blood supply can occur in small or large blood vessels.

o   Acute pain crises are the cause of most SCD-related hospitalizations and are typically localized to one area such as the chest, back, abdomen, or joints. Most pain events are triggered by a viral or bacterial infection. Many patients will be able to distinguish pain from SCD from pain due to any other cause because of the recurrent nature of these acute pain crises.

o   Acute chest syndrome (ACS) is a vaso-occlusive crisis that affects the pulmonary system and is the most common cause of death from SCD. Diagnosis of ACS is made by a combination of acute chest pain, abnormal substances in the lungs detected on a chest x-ray, and low levels of oxygen in the blood. ACS is most commonly caused by infection, and additional signs to monitor for include cough, fever, wheezing, shortness of breath, and hyperventilation. It is important to institute prompt and aggressive management of ACS to prevent progression.

o   Chronic organ damage occurs from the long-term effects of vaso-occlusive episodes and limited blood flow to these organs. Organ systems that may be damaged include the nervous system, heart, lungs, liver, reproductive system, urinary system, bones, skin, and eyes.

What is the treatment of SCD?^1,3,6,7

v  Oxygen is given to patients experiencing acute pain crises to minimize the risks of low oxygen levels in the blood, which can cause further sickling of the RBCs.

v  Antibiotics are given if doctors suspect a bacterial infection is present, since SCD patients are at a high risk of life-threatening bacterial infections. Some cases of ACS are difficult to differentiate between pneumonia, so patients with ACS will often be treated with antibiotics. Some patients are treated with penicillin as a preventative measure if they are viewed as a higher risk for developing future infections.

v  Pain management

o   This is an important aspect in the care of patients with SCD. The main goal of therapy is to relieve pain and allow patients to maintain maximal functional ability, and pain management regimens should be tailored to each patient.

o   Mild to moderate pain may be treated with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen. An opioid pain medication may be added if pain is persistent.

v  Hydroxyurea

o   The goal of therapy for SCD is to prevent the sickling of RBCs and increase the production of fetal hemoglobin (HbF) in the blood to inhibit abnormal RBC aggregation. HbF is a form of hemoglobin that comprises approximately 1% of total hemoglobin, although it is the predominant form of hemoglobin before birth. HbF helps reduce RBC aggregation due to its high affinity for oxygen in the blood. The higher the HbF levels, the less RBC sickling will occur, resulting in fewer pain crises.

o   Benefits of hydroxyurea therapy include increased hemoglobin levels, decreased destruction of RBCs, and a significant reduction in permanently sickled cells in the blood, all of which will help reduce the frequency of acute pain crises.

v  Exchange transfusion is a process that removes a patient’s blood and replaces it with blood without sickle cell hemoglobin. These transfusions are sometimes required during episodes of ACS to prevent progressive vaso-occlusion.

v  Stem cell transplant is a newer treatment option that is still being studied for its effectiveness and safety. It is the only potential curative option but comes with many risks and financial costs.

Where can I find more information on SCD?

v  Centers for Disease Control and Prevention

o   http://www.cdc.gov/ncbddd/sicklecell/index.html

o   Contains free materials and helpful patient tip sheets

v  American Sickle Cell Anemia Association

o   http://www.ascaa.org/

v  Sickle Cell Kids

o   http://www.sicklecellkids.org/

v  Sponsored by the Sickle Cell Disease Association of America

o   http://www.sicklecelldisease.org/

Written by:

Emily Kim, PharmD Candidate, 2015

UIC College of Pharmacy

References

1. Chan C, Frei-Jones M. Sickle Cell Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach. 9^th ed. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811488. Accessed August 26, 2014.

2. Benz EJ Jr. Disorders of Hemoglobin. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine. 18^th ed. New York, NY: McGraw-Hill; 2012. http://accesspharmacy.mhmedical.com/content.aspx?bookid=331&Sectionid=40726842. Accessed August 26, 2014.

3. Bunn H. Sickle Cell Disease. In: Bunn H, Aster JC. eds. Pathophysiology of Blood Disorders. New York, NY: McGraw-Hill; 2011. http://accessmedicine.mhmedical.com/content.aspx?bookid=676&Sectionid=44827775. Accessed September 2, 2014.

4. Sickle Cell Disease. Centers for Disease Control and Prevention website. http://www.cdc.gov/ncbddd/sicklecell/index.html. Updated July 14, 2014. Accessed September 2, 2014.

5. Schrier SL. Red blood cell survival: Normal values and measurement. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate; 2014. www.uptodate.com. Accessed September 26, 2014.

6. Preboth M. Practice guidelines: management of pain in sickle cell disease. Am Fam Physician. 2000;61(5):1544-1550.

7. NICE clinical guideline 143: Sickle cell acute painful episode: management of an acute painful sickle cell episode in hospital. National Institute for Health and Clinical Excellence website. http://www.nice.org.uk/guidance/cg143/resources/guidance-sickle-cell-acute-painful-episode-management-of-an-acute-painful-sickle-cell-episode-in-hospital-pdf. Published June 2012. Accessed September 2, 2014.