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Sicklepedia: Online Sickle Cell Encyclopedia

Sickle Cell, A Blood Disorder

Overview

Sickle cell is a blood disorder passed down from parents to children. It is characterized by sickle or crescent-shaped red blood cells that are unable to carry oxygen sufficiently through the body, causing a range of complications.

 

Sickle cell is caused by certain changes in the DNA code or a mutation. All people with sickle cell disease inherited a specific mutation that changes the way some of their blood cells function. Normally, red blood cells are round and flexible and can travel easily through blood vessels; however, in people with sickle cell disease, their red blood cells transform into brittle, sticky and crescent (or sickle) shaped cells called sickle cells.

 

Due to their shape and consistency, sickle cells become unable to move freely through small blood vessels, which can block or slow down blood flow to all of the tissues beyond that point, this is called vaso-occlusion, or a vaso-occlusive pain crisis. Your blood flows all throughout the body, therefore any organ (like the kidneys) or tissue (like muscles) could be affected. 

 

This loss of blood flow causes a shortage of oxygen to the affected body parts and organs. When the oxygen level is too low, injuries and even cell death occurs. This complication causes damage that builds up as time goes on. In addition to the loss of blood flow, sickle cells break down very easily and rapidly (called hemolysis) in the bloodstream, causing a shortage of blood cells, or anemia, and releasing content that can be toxic in high levels. 

 

All of these events inside the body can cause extreme pain, damage to organs and several other complications that contribute to the negative impact of sickle cell disease.

 

Genetic Inheritance

 

Genes hold information that determines your traits or characteristics. They are passed down from parents to each of their children. This means that you receive two “copies” of most genes. Small differences in the code can have a major positive or negative impact. Many of your noticeable characteristics, such as eye color, height and hair texture, are inherited from your parents– such is the same for sickle cell disease. Sickle cell disease can only be passed down from generation-to-generation in the DNA. This means sickle cell

disease is not contagious and it cannot be caught or transferred through contact– only through genetic inheritance.

The following is the likelihood of parents passing sickle cell on to each child:

 

If both parents have sickle cell disease, there are no unaffected genes available to pass on. There is

  • 100% chance of sickle cell disease with each pregnancy 

 

If one parent has sickle cell disease and the other parent does not have the disease or the trait, with each pregnancy there is

  • 100% chance that each child will receive one copy of the sickle gene (sickle cell trait)

  •  0% chance of having a child with sickle cell disease

 

 

If each parent has sickle cell trait, inheritance patterns are more complex. With each pregnancy, each parent could pass down a disease-linked allele (S) or a standard beta globin allele (A). The combinations could result in a baby with sickle cell disease, sickle cell trait, or an unaffected child. Every single pregnancy has these three potential outcomes. If you compare the chances of each combination there is

  • 25% chance of sickle cell disease

  • 50% chance of one copy of the sickle cell gene (sickle cell trait)

  • 25% chance of no sickle cell gene 

 

Hemoglobin (pronounced heem-oh-glow-bin) is the protein in red blood cells (RBCs) that captures oxygen in the lungs and carries it throughout the body and releases it. Unaffected hemoglobin is labeled with the letter A. Variant forms of hemoglobin function in unexpected ways, like in sickle cell. The sickle cell gene variant is labeled ‘S’. You receive a copy of each gene from your biological mother and one copy from your biological father; therefore, your genes are labeled with two letters. This is called your genotype. For example,

 

  • AA means a person is unaffected by sickle cell disease. They inherited two normal hemoglobin genes, one from each parent.

  • AS means a person has one unaffected gene and one sickle cell gene. This is sickle cell trait.

  • SS means a person has two sickle cell genes, one from each parent. This is sickle cell disease.

  • SC means a person has one sickle cell gene and another hemoglobin mutation. This is sickle cell disease.

 

Example: “I have sickle cell anemia. My genotype is HbSS.”

 

Types of Sickle Cell Disease​

 

There are many types of sickle cell disease, however, the most common types of sickle cell disease are sickle SS disease or sickle cell anemia (hb SS), sickle SC disease (hb SC), sickle beta-plus thalassemia (hb Sβ+ Thal) and sickle beta-zero thalassemia (hb Sβ0 Thal).

 

Any hemoglobin gene mutation paired with the sickle cell gene causes sickle cell disease. Sickle cell anemia (hb SS) is the most common form of sickle cell disease followed by sickle SC disease and sickle beta thalassemia.

 

Other rare types of sickle cell disease include sickle SD disease, sickle SE disease, and sickle SO disease. There are thousands of hemoglobin mutations, which means new, but rare forms of sickle cell disease will be discovered.

 

Who Is Affected

 

Global

Sickle cell disease and trait affects millions of people globally and is particularly common among those whose ancestors come from sub-Saharan Africa. Sickle cell is also more common in:

 

  • Hispanics from Central, South America and the Caribbean

  • People of Middle Eastern (Saudi Arabia, Bahrain and Oman) descent

  • People of Mediterranean (Turkey, Greece and Italy) descent

  • People of Southeast Asian (India) descent

Did You Know

There is a common misconception that sickle cell disease only affects those of Africans descent.

 

Due to migration, slavery and

other factors, sickle cell can be found in all races and ethnicities across the world, which makes

it a global health issue.

About 5% of the world’s population carries a hemoglobin mutation gene, the majority of them being sickle cell and thalassemia. These conditions are common in regions that have widespread malaria. There are twice as many babies born with sickle cell anemia (SS) than all of the major thalassemia types combined.

United States

In the United States, the CDC estimated that:

 

  • SCD affects approximately 100,000 Americans.

  • SCD occurs among about 1 out of every 365 Black or African-American births.

  • SCD occurs among about 1 out of every 16,300 Hispanic-American births.

  • SCD occurs among about 1 out of every 100,000 Caucasian births.

  • About 1 in 13 Black or African-American babies is born with sickle cell trait (SCT).

Did You Know

The average lifespan of a normal red blood cell is about 120 days compared to sickle cells which

last about 10 to 20 days or less.

 
 
 

History​

 

It is hypothesized that the sickle cell gene has been present in Africa for as long as 7,000 years. Although sickle cell disease was widely known in Africa, it wasn’t discovered in Western medicine until 1910.

 

Walter Clement Noel was the first person described with sickle cell disease. Noel was a dental student from Grenada, who studied in Chicago. When experiencing a pain episode, Noel sought out medical care at a neighborhood hospital. Noel was assigned to Dr. Ernest Irons who was a medical resident of cardiologist Dr. James Herrick.

 

When Irons looked at Noel’s blood under a microscope, he saw red blood cells shaped like a ‘sickle’ as medical literature describes. Herrick later published the first paper entitled, “Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia”. Irons continued to care for Noel until he returned to Grenada, where he died in May 1916 at the age of 32 years from acute chest syndrome.

 

In 1951, Dr. Linus Pauling and Dr. Harvey Itano were the first to coin the term “molecular disease”, a disease caused by proteins with abnormal structures, like the hemoglobin molecules that cause sickle cell disease.

Did You Know

In 1949, sickle cell disease was the first molecular disease discovered in history.

In 1956, Dr. Vernon Ingram and Dr. J.A. Hunt showed that a mutation replacing one amino acid with another was the underlying cause for the abnormal hemoglobin and distorted shape of red blood cells in sickle cell disease.

In 1983, the first successful cure for sickle cell disease was reported when a bone marrow transplantation meant to cure a child with acute leukemia also cured her sickle cell disease.

Complications​

 

Sickle Cell Disease

Signs and symptoms of sickle cell disease are different from person to person and can range from mild to severe. There are many factors that influence the severity of sickle cell disease– even siblings may not have the same degree of severity.

 

Sickle cell complications commonly start in early childhood at around four to six months of age. One of the first signs a baby has sickle cell disease is dactylitis, the swelling of their hands and feet. However, in the United States all newborns are screened for sickle cell disease.  In countries where there is no screening dactylitis, severe infections, and anemia often lead to the diagnosis of sickle cell disease.

 

Many of the complications found in sickle cell disease are the result of hemolysis; the rapid breakdown of red blood cells, other complications of sickle cell disease are due to the stickiness of red cells, white and anemia; the decreased number of red blood cells. Complications can be acute which typically develop suddenly or chronic which develop over time.

Did You Know

Fetal hemoglobin, which is found in high amounts in babies, has anti-sickling properties because it is good at carrying oxygen.

Acute or sudden complications include:

  • Pain crises (vaso-occlusive episodes)

  • Infections

  • Acute chest syndrome

  • Stroke​​

 

  • Splenic sequestration

  • Severe anemia caused by parvovirus B19

  • Priapism

  • Dactylitis (Hand-Foot Syndrome) (infants)

Chronic or complications that occur over a longer period of time include:

  • Anemia due to the increased breakdown of blood cells

  • Pulmonary hypertension

  • Avascular necrosis

  • Leg ulcers

  • Eye complications (retinopathy)

  • Chronic kidney disease

  • Heart disease

  • Iron overload from blood transfusions

  • Liver disease/gallstones

 

 

Sickle Cell Trait

Under extreme conditions like low oxygen levels in the air, dehydration, and high altitude and increased pressure in the atmosphere, red blood cells of individuals of sickle cell trait can sickle and lead to medical complications. Additionally, chronic kidney disease and a very rare form of kidney cancer (renal medullary carcinoma) are also associated with sickle cell trait.

Diagnostic Testing

 

During pregnancy:

 

Testing for sickle cell can be performed during pregnancy. A prenatal test can be conducted to find out if the fetus has sickle cell disease or sickle cell trait by collecting a sample of the amniotic fluid, the fluid around the baby. Chorionic villus sampling, a DNA test, is an additional way to test the baby’s sickle cell genetic status. Additionally, there is also ongoing research to test maternal blood for fetal DNA.


 

Newborn Screening:

 

Newborn screening consists of a heel-prick blood sample that is then analyzed for abnormal hemoglobin. This test can identify both sickle cell disease and sickle cell trait. Universal newborn screening for sickle cell is required in every state in the United States. In the European Union not all countries screen for sickle cell disease.  In sub-Saharan Africa, there is very little screening.


 

Blood Test:


For children and adults who are unsure if they have the sickle cell gene or any abnormal hemoglobin, they can find out with a simple blood test, provided by a healthcare provider. A hemoglobin electrophoresis test can determine if an abnormal hemoglobin gene is present, however, if a rare abnormal hemoglobin gene is detected, additional tests may be needed to confirm genetic status.

Treatments

 

Treatment options for sickle cell disease vary based on resources available and the associated complications. Below are some commonly recommended treatments and preventative measures for sickle cell disease complications.

 

 

Preventative care

 

Antibiotics

It is recommended that babies diagnosed with SCD should begin taking penicillin as early as two months of age to prevent life-threatening infections.

 

Vaccinations

Another way to prevent infection is to stay up to date with vaccinations.

 

Blood Transfusions

 

Simple blood transfusion: A simple blood transfusion adds healthy blood to the body to dilute sickle cells.

 

Chronic transfusion: Simple transfusions scheduled generally every two to four weeks. This therapy is usually for individuals with sickle cell disease that have a high stroke risk or other life-threatening complication of sickle cell disease.

 

Exchange transfusion: Sickle cell affected blood is removed and replaced with healthy blood cells, this can be done manually by a nurse or with a machine which performs an automated red cell exchange.

 

 

FDA Approved Drugs

 

Hydroxyurea

Boosts the production of fetal hemoglobin, which prevents the formation of sickle cells. Hydroxyurea was FDA approved in 1998 and is a recommended treatment option for sickle cell disease.

 

The FDA approved hydroxyurea for children as young as 2 years in 2017.  Some centers that start hydroxyurea earlier than two years.

 

 

L-glutamine

Regulates and prevents oxidative damage in red blood cells. L-glutamine was FDA approved in 2017.

 

Pain Management

 

  • Opiates (orally or by IV)

  • NSAIDS

  • Over the counter painkillers such as ibuprofen and for very young children acetaminophen

  • Alternative treatments such as heat therapy, meditation, and/or cannabis

 

 

Additional treatments

Folic acid

Can boost red blood cell production to help with anemia symptoms if there is folate deficiency.

 

 

Curative

Bone marrow transplant: This is currently the only known cure for sickle cell disease and is also referred to as stem cell transplant. This is currently the only known cure for sickle cell disease and is also referred to as stem cell or progenitor cell transplant. An HLA matched donor, usually a sibling is required, however, there is a study in adults to use a relative who is a “half” match, like a parent, for the stem cells.  

 

Studied Therapies

Gene therapy: Scientists are testing three key methods to modify stem cells for sickle cell disease, which are still in the study phase and you would have to enroll to have the procedure.

  • A virus is used to insert a viable copy of the hemoglobin gene into the stem cell.

  • Block the gene that turns off fetal hemoglobin and turns on adult hemoglobin allowing patients with sickle cell disease to produce fetal hemoglobin instead.

  • Gene editing with CRISPR, a tool that lets scientists snip out parts of genes and paste in new sections.

 

 

Additional studied therapies:

  • Voxelotor: An oral drug being studied that prevents red blood cells from transforming into sickle cells. This decreases hemolysis and anemia and increases oxygen delivery.

  • Olinciguat: An oral drug that replenishes the amount of nitric oxide. Low amounts of nitric oxide in sickle cell disease causes inflammation, stickiness in blood vessels, causes blood vessels to close, blocking blood flow, and decreasing blood supply to organs.

  • IMR 678: An oral drug that reduces sickling and blockages caused by sickle cells within blood vessels.

  • Crizanlizumab & Rivipansel: An drug administered through monthly IV infusions, that prevents adhesion or the clumping of sickle cells within blood vessels, preventing pain or vaso-occlusive crises.
     

It is always highly recommended that a patient consults with their primary care provider or hematologist to ensure the right and best treatment options, preventative options, and clinical studies are right for them individually.

Resources

 

Below are some resources those living with sickle cell disease and their loved ones.

 

Digital Informational Resources

 

Sickle Cell 101

A nonprofit organization dedicated to providing patient-friendly educational material globally for sickle cell disease and trait through its digital platforms including its website, social media pages and dissemination of literature. Visit http://sc101.org | Literature downloads

 

oneSCDvoice

An online platform that brings educational resources to those with sickle cell disease. It connects people with other patients as well as doctors. Visit http://onescdvoice.com

 

Sickle Cell Information Center

A website that provides sickle cell patient and their families and health care providers with professional education, news, research updates and access to sickle cell resources worldwide. Visit http://scinfo.org

 

A Parent’s Guide to Sickle Cell Disease

A guide by the New England Newborn Screening Program. This resource is for parents of children born with sickle cell disease. It includes tips on how to manage their health, organizing your child’s care, and special treatments for sickle cell disease. View PDF

 

National Resource Directory by State

A CDC compiled list of community-based organizations groups for sickle cell disease patients and families in each state. Visit directory