Sickle Cell Disease Management: The Role of SLPs and Audiologists, Part 1

Editor’s Note: This text is a transcript of the course, Sickle Cell Disease Management: The Role of SLPs and Audiologists, Part 1, presented by Candice J. Adams-Mitchell, SLP.D, CCC-SLP.

Learning Outcomes

After this course, participants will be able to:

• Define the various types of Sickle Cell Disease.
• Describe the communicative, neuropsychological and audiological implications of Sickle Cell Disease.
• Describe current treatment options for Sickle Cell Disease.

Introduction

This course is Sickle Cell Disease Management: The Role of SLPs and Audiologists. Some might think, "Oh, I know a person who has sickle cell disease," or some of you might have the disease yourself. But sickle cell disease is a group of inherited red blood cell disorders affecting millions of individuals throughout the world. The CDC estimates that approximately 300,000 people worldwide have sickle cell disease, with about 100,000 in the United States. Sickle cell disease is associated with an increased risk of early death and has adverse clinical complications impacting various organ systems. In turn, patients with sickle cell disease and their families report significantly diminished quality of life from childhood to adulthood. 

What exactly is sickle cell disease? Here is a simple explanation. Our red blood cells contain a special protein called hemoglobin which carries oxygen from the lungs to all parts of the body. A person who has sickle cell disease has the substance amino acid valine instead of glutamic acid.  This small adjustment is in a place where there should be glutamic acid. While that seems like a small adjustment, this change causes the chemicals in your red blood cells to form long strings causing the red blood cells to be deformed into a sickle-like shape. When sickle red blood cells give up their oxygen, that causes them to clump together and become very sticky. Essentially, it forms long, red rods inside the red blood cells. Those red blood cells, in turn, become very rigid and inflexible, and that sickle-like shape cannot squeeze through small blood vessels and creates a blockage. That blockage causes less oxygen to reach the tissues in the body. 

Those blood cells last only 20 days, compared to 120 days for normal red blood cells. After recurrent episodes of sickling, damage starts to occur, and those cells cannot resume their normal biconcave disc shape.  Persons with sickle cell disease remain in a chronic state of anemia because their bodies cannot attain adequate oxygen from their red blood cells.

History of Sickle Cell Disease

Sickle cell disease was first introduced to modern medicine in 1910 when physician James Herrick discovered sickle cell anemia in the Western world while treating a 20-year-old patient from the West Indies.  It wasn't until 1922 that the term 'sickle cell anemia' was coined when physicians were treating patients with this disorder.  It was obviously based on seeing these peculiar sickle-shaped red blood cells.  Today, sickle cell disease refers to sickle cell anemia, sickle cell variants, and sickle cell trait, which is why I referred to it as a group of blood disorders earlier. 

The historical background of sickle cell disease is one that many people don't know about and one that I think is important to explain whenever I talk about sickle cell disease. Sickle cell disease came about because of an error in our hemoglobin gene resulting from a genetic mutation that occurred thousands of years ago in parts of Africa, the Mediterranean basin, the Middle East, and India. A deadly form of malaria was very common at the time. And malaria epidemics were causing a great number of deaths. In areas where malaria was a problem, children who had inherited one sickle hemoglobin gene and carried the sickle cell trait had a survival advantage unlike children who had the normal hemoglobin genes who were type AA. These children who had that sickle cell trait survived the malaria epidemics. Those children grew up, had their own children, and passed on the sickle hemoglobin gene to their children.

As populations migrated, the sickle cell mutation spread to other Mediterranean areas. It spread further into the Middle East and eventually into the Western hemisphere. In the United States and other countries where malaria is not a problem, the sickle hemoglobin gene no longer provides that survival advantage it once provided for those individuals. Instead, it's a serious threat to the carriers' children. A person with sickle cell trait is a threat to their children because those individuals may inherit two abnormal sickle hemoglobin genes and, as a result, have sickle cell anemia.

As I previously stated, sickle cell disease is caused by a mutation in your hemoglobin. That mutation is in the hemoglobin beta (HbB) gene inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one from the father and one from the mother.  Recessive genetic disorders occur when an individual inherits the same altered gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, that person will be a carrier for the disease but usually won't show any symptoms. The risk comes into play when two carrier parents pass the altered gene onto their children. When this happens with sickle cell disease, that means that for each pregnancy, there is a one in four chance that those parents will have an affected child with sickle cell disease.  If two parents have the sickle cell trait, there is a 25% chance that they will have a child who has sickle cell disease. The risk of having a child who is a carrier or has sickle cell trait like the parents with each pregnancy is 50%. And the chance of a child receiving normal genes (i.e., type A hemoglobin from both parents) is one in four.  Again, for each pregnancy, there is a one in four chance that the parents will have a child with sickle cell disease, a one in two chance that they will have a child who carries a sickle cell trait, and a one in four chance that they will have a child who has type AA hemoglobin and is not a carrier for the disease.

Sickle Cell Trait

Sickle cell trait means there are two genes for hemoglobin. One is inherited from each parent. If one is a normal gene and one is an abnormal gene passed on by each parent, only half of that individual's hemoglobin will be produced abnormal. Therefore, that individual is considered a carrier for the abnormal gene. In terms of sickle cell, this is commonly referred to as having the trait of the disease. Sickle cell trait is present in one out of 10 African Americans.

In sickle cell trait, about half of the hemoglobin in the red blood cell is sickle-shaped, and the cell will exhibit sickling only under severe conditions. So, most people with sickle cell trait don't have any symptoms of sickle cell disease. In rare cases, people with sickle cell trait might experience complications of sickle cell disease, such as pain crisis, in their extreme form. Also, in rare cases, certain conditions can be harmful to persons with sickle cell trait.  For example, anytime they're in an area with increased pressure in the atmosphere, such as scuba diving, or when there's less oxygen in the air (e.g., mountain climbing or exercising extremely hard), that could be problematic for a person with sickle cell trait. Being dehydrated and having very little water in the body can be an issue for an individual with sickle cell trait. And lastly, if a person is in a place with a high altitude, that can be problematic for individuals with sickle cell trait.  More research is needed to understand why some individuals have sickle cell trait and don't experience any complications and why some individuals experience similar complications even though they have the full-fledged disease.

Variants of Sickle Cell Disease

Understanding the different variants of sickle cell disease is important. Suppose you have a patient that you are treating at a hospital or in a school setting. In that case, you need to understand what they might be experiencing based on their variant of sickle cell disease and how that may impact clinical treatment or what you're doing with that patient.

There are several types of sickle cell disease. The most common ones are:

• Hemoglobin SS (Sickle cell anemia)
• Hemoglobin SC (Sickle C disease)
• Hemoglobin SB + (Sickle beta thalassemia)
• Hemoglobin SB 0 (Sickle beta zero thalassemia)
• Hemoglobin SD, SE, SO (Sickle D, E, or O disease)

Sickle cell anemia, type SS, occurs when a child inherits one substitution beta-globin gene, the sickle gene, from both parents. This child has what is commonly called sickle cell anemia. Populations with a high frequency of sickle cell anemia are of African and Indian descent. This is considered the most severe type of sickle cell disease because the person has both SS genes. They experience severe anemia and severe pain because most of the red blood cells in their body are sickle-shaped. 

The next variant is Hemoglobin SC. These individuals have sickle hemoglobin C. They have a slightly difference substitution in their beta-globin gene that produces both hemoglobin C and hemoglobin S. Sickle hemoglobin C disease may cause similar symptoms as sickle cell anemia but because they don't have both SS genes, there is less anemia. Populations with a high frequency of sickle hemoglobin C disease are those of West African, Mediterranean, and Middle Eastern descent.

Individuals with sickle beta thalassemia disease, both + and 0, have substitutions in both beta-globin genes. The severity of this disease will vary in patients according to the amount of normal beta-globin they can produce. When no beta-globin is produced, these patients' symptoms will be identical to sickle cell anemia, with the most severe cases needing chronic blood transfusions. Populations with a high frequency of sickle beta thalassemia are of Mediterranean and Caribbean descent.

Sickle hemoglobin O disease is another substitution in the beta-globin gene that interacts with sickle hemoglobin. Why is that important? Because even if you don't have the sickle trait but have hemoglobin O and you have a child with someone who does have the sickle trait, the hemoglobin O interacts with that sickle hemoglobin. So, individuals with sickle hemoglobin O have similar symptoms of sickle cell anemia. Populations with a high frequency of sickle hemoglobin O disease are of Arabian, North African, and Eastern Mediterranean descent.

With sickle hemoglobin D disease, a different substitution of the beta-globin gene has been found to interact with the sickle hemoglobin gene. Individuals with sickle hemoglobin D have moderately severe anemia and occasional pain episodes. Populations with a high frequency of sickle hemoglobin D are those of Asian and Latin American descent.

How is Sickle Cell Diagnosed? 

Three tests are used to diagnose sickle cell disease: hemoglobin electrophoresis, sickle solubility test, and hemoglobinopathy. Sickle cell disease is usually found at birth with a blood test during routine newborn screenings.  Hemoglobin electrophoresis is a second blood test used to confirm the diagnosis.

Sickle cell disease can actually be diagnosed before a baby is born with a test for amniotic fluid or sample tissue from the mother's placenta, but there is a risk of miscarriage.  Electrophoresis, sickle solubility test, and hemoglobinopathy can be done after the baby is born. These tests are different ways to extract blood and detect the presence of hemoglobin in that individual's blood. Chemicals are added to isolate how much oxygen is present in that newborn red blood cell, which allows them to see if it's going to sickle, resume back to its normal red blood cell shape, sickle, and then does it stay.

Once you can see the percentage of how many sickled cells the baby has, that allows them to determine what type of sickle cell the child might have. They can look at the different types, the shapes of the sickled cells, and the shapes of the red blood cells. We know that children who have sickle beta-thalassemia are sometimes larger in nature. So they can determine the variant the child possibly has and if the child has sickle cell disease.

Prevalence of Sickle Cell Disease

We know that sickle cell disease affects primarily African Americans.  Around 100,000 Americans in the United States probably have sickle cell disease. And it occurs in about one out of every 365 African American births. One out of 10 of those births will be born with sickle cell trait. Continuing to break it down, one in 600 of those newborns will have sickle cell anemia or HBSS. One in 1500 will have type SC, and roughly one in 350 will have either SC, sickle beta thalassemia zero, or HBSS.

Hispanic Americans are the next population with the highest prevalence of sickle cell disease in the United States, with one in 172 having the sickle cell trait, and 1 in 1000 having sickle cell disease or a variant of it.

Sickle Cell Disease Complications

Anemia

Anemia is one of the main complications because the red blood cells only live for about 20 days as opposed to 120 for a person who doesn't have sickle cell disease. Because those red blood cells are dying early, there are not enough healthy red blood cells to carry oxygen throughout this person's body. As a result, the person will appear tired, irritable, possibly dizzy, lightheaded, have a fast heart rate all the time, possibly has difficulty breathing, and pale skin color. Although that is not always a good indicator because the person may never look pale depending on their skin tone. Jaundice (yellowing of the eyes), slow growth, and delayed puberty are complications of anemia because of the lack of adequate oxygen needed for organs and the other tissues in the body.

Musculoskeletal

Anemia and pain occur with sickle cell disease.  These are the two complications that are usually associated with the disease.  But sickle cell disease impacts multiple organs in the body. So, it is more than just a pain disease.

How do we get to this point? A baby is born with fetal hemoglobin (HbF).  Babies don't start to lose that fetal hemoglobin until around a year or so. Humans possess predominantly hemoglobin F in their fetal life. But then, about 12 weeks after birth, the body shuts off fetal hemoglobin and replaces it with hemoglobin A (HbA). In individuals who don't have a blood disorder such as sickle cell disease, when your fetal hemoglobin shuts off, it's making hemoglobin A. However, for a person who has sickle cell disease, when their body shuts off hemoglobin F, they start producing hemoglobin S (HbS). As a result, there is increased pain because the infant has vaso-occlusive pain crises. Vaso-occlusive crises occur because of the sickle-shaped cells. Remember, they're rigid. They're like wood. They're sticky and clumped together. They're trying to move through those small vessels, and they're getting obstructed. This causes ischemic injury to the organ that it's trying to supply blood to. And as a result, it causes excruciating pain for this population.

Vaso-occlusion is one of the main clinical complications of sickle cell disease. It results in pain, syndromes, stroke, leg ulcers, spontaneous abortions, and renal insufficiency. The sickle shape cells are trying to push through those areas and acute pain occurs because of ischemic tissue injury. However, these individuals are also impacted daily with chronic pain because of the destruction of their bones, joints, and other visceral organs due to their recurrent crisis. A vaso-occlusive crisis mostly involves the back, legs, knees, chest, and abdomen.  Avascular necrosis is another complication, which is the death of bone tissue due to the lack of blood supply.

Growth Retardation and Atypical Skeletal Development

Children with sickle cell disease often experience growth impairment and skeletal immaturity. These complications are related to bone marrow hyperplasia and subsequent ischemia due to localized anoxic events resulting in long bone asymmetry. Children and adolescents with sickle cell disease tend to be shorter and weigh less than their non-affected peers. The anemia causes infants to feed poorly due to fatigue and results in poor nutritional intake, impacting their overall growth. There are medications, hydroxyurea, and other medications that are used to decrease crises in individuals who have severe sickle cell disease and can support growth and development in these school-aged children when they need it.

Central Nervous System

The next complication is with the central nervous system. This is a big one. From the below list of complications, I have highlighted silent cerebral infarcts, ischemic stroke, and hemorrhagic stroke.

• Silent Cerebral Infarcts (39% by 18 years)
• Headache (both acute and chronic: 36% in children with sickle cell anemia)
• Ischemic Stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but 11% in children with SCA without screening)
• Hemorrhagic Stroke (3% in children with SCA and 10% in adults with SCA)
• Moyamoya Syndrome
• Posterior Reversible Encephalopathy syndrome
• Cerebral Fat Embolism
• Cerebral Venous Sinus Thrombosis

Sickle cell disease impacts the central nervous system. The misshapen cells block the major blood cells supplying oxygen to the brain resulting in severe brain damage. If a person has one stroke from sickle cell anemia, they're more likely to have a second and third stroke. The literature states that silent cerebral infarcts occur in approximately 39% of children. They've experienced a silent cerebral infarct by 18 years old, meaning they don't even know that these things are going on. If you look at the brain imaging of an individual with sickle cell disease, you will see that many of them have had multiple silent cerebral infarcts.

Ischemic stroke is as low as 1% in children with effective screening and prophylaxis. But it's about 11% in children who do not undergo the necessary screening. And, finally, hemorrhagic stroke occurs in about 3% of children who have sickle cell anemia and 10% of adults who have sickle cell anemia. 

Sickle Cell Disease Stroke Management: Transcranial Doppler.  What can we do about stroke management? Years ago, there was a push for stroke prevention. The program is called STOP, stroke prevention in sickle cell anemia.  As a result, this program has demonstrated that children who have transcranial dopplers done at least once a year can stop them from having a stroke. Transcranial doppler is a test similar to an ultrasound, which measures the velocity or the speed of blood flow through the blood vessels in the brain. It is a predictor for stroke risk and is performed annually on children with sickle cell disease.

Acute Chest Syndrome

While several complications of sickle cell disease affect the cardiopulmonary system, I will focus on acute chest syndrome because it's one of the most severe and fatal complications for persons who have sickle cell anemia. Acute chest syndrome is any new pulmonary infiltrate seen on a chest radiograph. It is usually accompanied by a fever and other respiratory symptoms, such as cough and chest pain.

Essentially, the sickling is happening in the chest. The person is having what might be considered a crisis in their chest. Because their sickling is happening in those small blood vessels in the lungs, which causes a pulmonary infarction or emboli, it's exacerbated if the person has viral or bacterial pneumonia. It is the second most common cause of hospitalization in patients who have sickle cell disease and is responsible for about 25% of death. Interestingly, there is a strong correlation between acute chest syndrome and neurological complications in these patients with sickle cell disease.

Hepatopathy

The liver is also affected by sickle cell disease. In addition to vascular complications from the sickling process, patients with sickle cell disease often receive multiple transfusions, which place them at risk for viral hepatitis, iron overload, and a combined effect of chronic hemolysis. These individuals could have pigment gallstones and other factors contributing to liver disease.  They can experience frequent right upper quadrant pain, nausea, vomiting, and fullness after meals.  Until they can get rid of the gallstones, they are in pain and aren't eating. So, you must figure out how to get adequate nutrition in these compromised patients.

Acute Splenic Sequestration

Acute splenic sequestration is another complication of sickle cell disease. The spleen is a small organ located in the upper left of the abdomen, under the rib cage. The spleen is at particular risk for complications from sickle cell disease because it filters blood. Sickled cells get trapped in the blood cells leading in and out of the spleen, and normal blood flow is blocked. That is called sequestration. The blood stays inside the spleen instead of flowing through it, and as a result, the spleen becomes enlarged. 

Babies and young children with sickle cell anemia are at the greatest risk of splenic sequestration. Those complications can occur from two months of age up to five years. After five, the spleen becomes smaller and, in most cases, can't enlarge anymore. However, children with sickle cell disease can experience complications anytime after age five. Ultimately, they will need a splenectomy, which is effective at preventing recurrent sequestration events. But it does put the child or adult at risk for infectious complications. So, these children are not in school, which we know will impact educational attainment. These are adults who aren't able to make it to work.

Dactylitis

Dactylitis is severe pain in both hands, feet, or both simultaneously. It is one of a baby's first symptoms of sickle cell disease and is caused by blocked blood circulation. Symptoms include extreme pain and tenderness, usually with swelling. A child can have an episode for one to four weeks. As you can imagine, fine motor skills are often affected due to pain and swelling of the hand.  Their writing can look very immature. (We will discuss our role in managing these patients with sickle cell disease in Part 2.

Genitourinary

You may see some issues with the genitourinary system that we don't necessarily deal with, such as priapism which is a prolonged erection of the penis. It can happen in children as well as adults.  This is an erection that is not caused by sexual stimulation but by poor blood flow through that organ. Children with sickle cell disease usually grow and develop more slowly and go through puberty about one to two years later than their peers.

Adults with sickle cell disease are often shorter and thinner than the general population. What does this mean for us as SLPs?  It might mean that males' voices don't match their age which can result in self-esteem and confidence issues.

Asthma

Asthma is a common comorbid factor in sickle cell disease because the incidence rates are much higher than expected compared to rates in the general population. So, whether asthma and sickle cell disease are purely related to genetic or environmental factors or a consequence of the underlying poor circulation, hemolytic and inflammatory state that's up for debate. Regardless of the etiology, we know that hypoxemia is induced by bronchoconstriction and inflammation. These individuals will have recurrent pain crises because asthma predisposes them to pain, acute chest syndrome, stroke, and increased mortality. Their breathing is very impaired compared to individuals in the general population who don't have asthma. So, this is a big deal for this population, especially when considering respiratory swallow coordination, etc.

Vision

As I mentioned, this is not just a pain disorder. As with all other complications,  blood cells can't move through and get trapped in the eyes. And, because they're sickling, they're getting stuck in the retina, which can cause vision problems. The worst-case scenario is the retina can loosen and lead to permanent blindness. This can happen to individuals without warning. 

Jaundice

Jaundice is a yellowing of the skin and eyes or the mouth. It's very common in sickle cell disease because those sickle cells don't live as long as normal red blood cells. Therefore, they're dying faster than the liver can filter them out. Bilirubin causes the yellow color from those broken-down cells. It starts to build up in their system, which causes that jaundice.

Immunological

There is a high incidence of immunological and bacterial infections in sickle cell disease, such as pneumonia, urinary tract infections, and septicemia. These infections occur mainly in our younger patients because of the spleen. Any infection in a child with sickle cell anemia is always treated as an emergency. Most of them are treatable and allow for complete recovery.

But keep in mind that these are children who don't have spleens. You might be seeing them every day in your school setting. You might be seeing them on your caseload. They may not be in pain, but they might be constantly sick if they don't have a spleen. So, once again, this impacts educational attainment.

Aplastic Crisis

Without going into detail, aplastic crisis simply means that the body stops making red blood cells. The body stops making red blood cells, and the child or adult will experience a very low drop in their hemoglobin. It usually happens in children who are under the age of 16. The only way to increase their blood count is through blood transfusions.

Treatment for Sickle Cell Disease

There is no cure for sickle cell disease. It is a very debilitating disease. But there are a few available treatments.

Blood Transfusions

One treatment is a blood transfusion. With a blood transfusion, a person with sickle cell disease is given healthy blood from another person (i.e., a donor).  Blood transfusions can help with anemia. They can also help when a person is in severe pain and has vaso-occlusion. Unfortunately, blood transfusions can't be done with everyone. When a person is exposed to several blood transfusions, they collect too much iron and can go into iron overload. The only way to get rid of iron is through iron chelation medication, which can help eliminate that excess iron.

A person can also develop antibodies to donors' blood and have a horrible allergic reaction to that person's blood. Iron chelation medications are important for removing excess iron from the blood, but they are considered ototoxic medications. 

Hydroxyurea

Hydroxyurea is a chemotherapy medication that increases hemoglobin F which makes red blood cells bigger, rounder, and more flexible, and hopefully less likely to return to their sickle shape.

Hydroxyurea has also been shown to prevent damage to the organs, and it causes fewer pain crises and acute chest syndrome. Once again, though, it's a chemotherapy drug. So, when you think about the patients you treat on chemotherapy drugs, they have vomiting and an upset stomach because it's an ototoxic medication. It causes chemotherapy-like symptoms for these patients and can also be problematic.

Bone Marrow Transplants

Lastly, bone marrow transplants can be used for treatment.  In a person with sickle cell disease, their bone marrow produces red blood cells that contain hemoglobin S. This will lead to complications for a person with sickle cell disease. The new bone marrow produces healthy red blood cells because they don't contain a lot of hemoglobin S. They wouldn't contain any HbS if they had a transplant from someone with normal hemoglobin. But for the patient who gets it from a person who has sickle cell trait, they could still produce S hemoglobin, but just a smaller amount.

But, an adult or child preparing for or having undergone a bone marrow transplant will not be in school or at work for a long time. It's very similar to those who undergo bone marrow transplants for cancer.  They are out of school or work for 6-7 months, they aren't around family, they are immunocompromised.  They undergo strong chemotherapy so their bodies don't fight the transplant.  Their speech and language, et cetera, mimic what we see in a person who has cancer. 

Gene Editing

Finally, there is an experimental treatment called CRISPR which is gene editing.   We don't know what it will do or if it will finally cure patients who have sickle cell disease. Essentially, cells are edited from two regions in the person's genome - HBG1 and HBG2.  The purpose of gene editing is to increase the production of fetal hemoglobin and red blood cells. Once again, the hope is the same as with any medication being provided to a person with sickle cell disease. If we increase the production of fetal hemoglobin, that will provide long-term benefits to those who have sickle cell disease. It will also improve blood flow, which will help with anemia, growth, nutrition, et cetera. As a result, these individuals will have fewer pain crises. Unfortunately, I think only three individuals have undergone gene editing, but that is not enough of a sample size to say it is promising for individuals with sickle cell disease. Cost also needs to be considered for this treatment.

Questions and Answers

Would you recommend two African American potential parents get tested before having children? Excuse me.

Yes. I definitely would because it is about those reproductive choices. For some, it may not matter if you have a child with sickle cell disease. For others, it's more about informed reproductive choices. I'm not saying, "Don't have children." But I do think parents should be informed that, "I carry this trait. My husband carries this trait." Even if it's not type S for both of you. I would definitely encourage parents to know their sickle status. And there are several platforms out there for persons who are carriers and desire not to have children with sickle cell disease.

Is there a universal screening that is done when babies are born?

We have implemented a newborn screening. Unfortunately, most individuals who probably were born in the '80s in a state where newborn screenings were not a theme. So, those individuals might not know their sickle status. But now it's a standard and part of the normal newborn screening. Those individuals with abnormal hemoglobin receive a letter stating that they need to follow up, that there is a deficiency or it's believed that they have a red blood cell disorder. They do not address whether or not it's sickle cell or not. They advise you to follow up with your physician and your pediatrician. And that's where they perform electrophoresis to determine if it is indeed sickle cell disease.

What type of pain meds are prescribed for sickle cell survivors?

These are patients who are on chronic pain medications. They are on the heavy, heavy narcotics and are often called "drug seekers" which is not true. These patients are on morphine and other heavy narcotics to try to help them manage the pain. But these patients have been in chronic pain all their life, so they have been on these heavy doses of pain meds pretty much all of their lives. And as a result, they don't have the effect that they might have on someone who only has to take them once or even occasionally.  Obviously, these pain meds can also cause impairment. 

Regarding some of the treatments you described at the end, such as a bone marrow transplant, do they have to have that multiple times? Or is it assumed that if they go through it once, that should be enough to get the red blood cells, and so they wouldn't have to do the procedure again? 

That is a wonderful question. The assumption is that once an individual undergoes a bone marrow transplant, they would only have to undergo it once. However, they do fail. And that's why it is not a cure. These are individuals whose immune systems have been wiped out.  They may be infertile.  So, there is a lot to consider for a bone marrow transplant. For children who undergo bone marrow transplants, parents have to think about all of that. In an effort to save their lives, there is a good chance that you're robbing them of the ability to produce life later because of the strong chemotherapy medications and things that they have to undergo. 

What is the life expectancy for someone with sickle cell disease?

It is a lot better than it used to be. I think we usually say between 50 to 60 years old. But you can still see patients who are 80 years old who have sickle cell disease. That's why I think it's important for us to get involved because other than normal aging processes that our bodies undergo, these individuals have had their body wreaking havoc on itself for their entire life, and they're living a lot longer than they used to. Nobody has thought about what their hearing looks like when they've been on iron chelation medications all their life or when they've been on hydroxyurea since ten months old because that's a chemotherapy drug. Nobody has been looking at those things or talking about those things. So, we need to be looking at what is our role now that these patients are living a lot longer than they used to.