© 2018 by Janelle E. Letzen, PhD

 
Sickle Cell Disease
What is Sickle Cell Disease (SCD)?

SCD is a group of genetic red blood cell disorders that can result in serious health complications and reduced quality of life. It affects millions of people worldwide. Importantly, SCD research is under-funded, stressing the need for lots of public awareness to make SCD a global health priority.

Why does SCD result in health consequences?
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When you think of red blood cells (RBCs), you might imagine bouncy disks flowing steadily through blood vessels. These RBCs contain a protein, called hemoglobin, that helps carry oxygen around the body to our organs. What is this oxygen transportation important? Well, just like humans need to breathe oxygen to survive, tissue around the body needs oxygen to stay healthy. 

In some people, RBCs look like someone squished the disk, resulting in a “sickled” shape. Because of this shape, sickled RBCs don’t flow smoothly through blood vessels. Instead, they can get trapped, reducing healthy blood flow carrying oxygen to organs around the body. As a result, these individuals can experience life-threatening medical problems and episodes of terribly high pain.

SCD Pain

Episodes of intense SCD pain are called "vast-occlusive crises." Crises can start 

or build quickly. Although a lot of people living with SCD know certain triggers for these pain episodes (like cold weather causing blood vessels to constrict), the episodes can also happen out of nowhere. Crises are one of the main reasons that people with SCD need emergency care. During less severe crises, individuals can sometimes manage the pain at home.

 

Because sickled RBCs cause oxygen to be cut off from healthy tissue, other health complications can happen. Common complications include long-term eye damage, acute chest syndrome (a condition similar to pneumonia that can be life threatening), avascular necrosis (death of bone tissue), stroke (brain bleed), and chronic pain that is separate from severe pain crises. In fact, the average lifespan for people with SCD is about 30 years shorter than average. 

Health Complications
Who does SCD affect?

SCD is the most common inherited disease. This means that it is NOT contagious as once believed. Instead, the presence of SCD is based on genetics.

Think back to your high school biology class where your homework might have been to complete Punnett squares, or graphs of possible genetic outcomes for children given their parents’ alleles, or gene variation. At the most basic level, dominant alleles show 

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their parents’ alleles, or gene variation. At the most basic level, dominant alleles show their associated traits even when the person only has one of them. Recessive alleles show their associated traits only when the person has 2 recessive alleles.

SCD is inherited through recessive genes. This means that a person must have one SCD allele from each parent in order to have the full symptoms of SCD. On the other hand, a person who inherits only one SCD allele does not experience the full array of SCD symptoms but does carry the allele

genetically. If he/she has children with a partner who either has SCD or also has the trait, their child can have SCD.  

Importantly, SCD is considered a minority health condition, meaning it is a disease that mostly affects people from a racial or ethnic minority. SCD can affect people from all races but is overwhelmingly experienced by Black individuals. Research suggests that people with SCD typically experience poorer quality healthcare than other patient populations. Given this disparity in healthcare, it is vital to raise awareness about SCD personal experiences and gaps in research.
 

What is it like to live with SCD?

Living with SCD can be challenging and exhausting. Most people with SCD have to manage symptoms of SCD (like acute pain episodes) and medical complications (like eye damage and acute chest syndrome) their whole life. There are no obvious physical signs that someone has SCD. It is sometimes called an “invisible,” chronic disease because others around them do not know the extent of pain or other symptoms that they experience on a daily basis.

There is a solid amount of pediatric patient resources for children who suffer from SCD. Because SCD patients are now living longer than in the past, these resources become limited for adults. For example, many healthcare financial programs are no longer an option for adults. So, on top of self-managing the symptoms listed above, adults with SCD must deal with high medical expenses and still try to do all of the home and work tasks that people without SCD do (e.g., take care of kids, hold a steady job). Understandably, these stressors can increase the risk of depression, anxiety, and sleep problems among people with SCD, which can in turn make their SCD symptoms worse.  

Some things that can help improve the quality of life in people with SCD include staying hydrated, using mindfulness strategies, taking folic acid supplements, avoiding extreme temperatures, exercising cautiously, and creating a support system. 

How is SCD treated?

Can we cure sickle cell disease (SCD)? For some very lucky people in who all of the stars align, the answer is yes! Allogeneic marrow transplants (aka stem cell transplants) are actually curative. What does bone marrow have to do with blood? Bone marrow is the tissue inside of bones where blood system stem cells live. Stem cells in bone marrow go through a process called “hematopoiesis,” becoming RBCs, white blood cells, and platelets. Because of these “hematopoietic” stem cells, bone marrow is the main site for blood system cell production. In an allogeneic bone marrow transplant, donor bone marrow replaces marrow in someone with SCD. The Warrior now has hematopoietic stem cells that produce bouncy RBCs daily instead of sickled RBCs. 

 

There are lots of barriers and risks to transplant. For example, donors must have a very close match on genes that help the immune system recognize foreign proteins. It’s estimated that <14% of Warriors have a match. Without a match, the transplant will be rejected, causing serious health risks. Also, transplants are only available in developed countries. As a result, these transplants are not usually an option.

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For most people with SCD, strongly recommended treatments include hydroxyurea and transfusion therapy. First, hydroxyurea is one of the only approved medications for SCD (sickle cell anemia subtypes). Remember how SCD is primarily a problem with hemoglobin? Well, hydroxyurea works to raise levels of hemoglobin, resulting in a higher ratio of healthy RBCs to sickled RBCs.

 

Blood transfusion therapy can also increase the number of healthy RBCs in blood temporarily, but is mainly recommended for people with worsening symptoms because of iron overload risk. In the most common transfusion method, sickled RBCs are removed from blood and replaced with healthy RBCs from a donor. Why can't we use donated blood to cure SCD? The human body needs about 100 billion blood system cells daily. That means lots of new donated blood each day! Donated blood is limited in supply and can lead to a buildup of iron in the body or immune system rejection. Although Warriors with severe risks (like reduced blood flow to the brain or lungs) rely on blood transfusions, it’s only a temporary treatment.

Other treatments include symptom management strategies. These strategies are things like medications and evidence-based psychotherapies teaching coping skills for pain, depression, anxiety, and insomnia. As you can imagine, all of these treatments take lots of time and money, which can be very burdensome for people living with SCD!

References

[1] US Center for Disease Control

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[3] Smith, L. A., Oyeku, S. O., Homer, C., & Zuckerman, B. (2006). Sickle cell disease: a question of equity and quality. Pediatrics, 117(5), 1763-1770.

[4] McGann, P. T. (2016). Time to invest in sickle cell anemia as a global health priority. Pediatrics, e20160348

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[7] Miko, I. (2008) Genetic dominance: genotype-phenotype relationships. Nature Education 1(1):140

[8] Berg, J. M. (2002). Tymoczko JL, Stryer L. Biochemistry. Hemoglobin transports oxygen efficiently by binding oxygen cooperatively. p. 155.

[9] Brandow, A. M., Zappia, K. J., & Stucky, C. L. (2017). Sickle cell disease: a natural model of acute and chronic pain. Pain, 158(Suppl 1), S79

[10] Quinn, C. T. (2016). Minireview: clinical severity in sickle cell disease: the challenges of definition and prognostication. Experimental biology and medicine, 241(7), 679-688

[11] Chaturvedi, S., & DeBaun, M. R. (2016). Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years. American journal of hematology, 91(1), 5-14.

[12] McClish, D. K., Smith, W. R., Levenson, J. L., Aisiku, I. P., Roberts, J. D., Roseff, S. D., & Bovbjerg, V. E. (2017). Comorbidity, pain, utilization, and psychosocial outcomes in older versus younger sickle cell adults: the PiSCES project. BioMed research international, 2017.

[13] Matthie, N., Hamilton, J., Wells, D., & Jenerette, C. (2016). Perceptions of young adults with sickle cell disease concerning their disease experience. Journal of advanced nursing, 72(6), 1441-1451.

[14] Jonassaint, C. R., Jones, V. L., Leong, S., & Frierson, G. M. (2016). A systematic review of the association between depression and health care utilization in children and adults with sickle cell disease. British journal of haematology, 174(1), 136-147.

[15] Mayo Clinic “Sickle Cell Disease – Lifestyle and home remedies; Coping and support"

[16] Bolaños-Meade, J., & Brodsky, R. A. (2014). Blood and marrow transplantation for sickle cell disease: Is less more?. Blood reviews, 28(6), 243-248.

[17] Yawn, B. P., Buchanan, G. R., Afenyi-Annan, A. N., Ballas, S. K., Hassell, K. L., James, A. H., ... & Tanabe, P. J. (2014). Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. Jama, 312(10), 1033-104.

[18] McGann, P. T., & Ware, R. E. (2015). Hydroxyurea therapy for sickle cell anemia. Expert opinion on drug safety, 14(11), 1749-1758.

[19] Chou, S. T. (2013). Transfusion therapy for sickle cell disease: a balancing act. ASH Education Program Book, 2013(1), 439-446.