Sickle Cell Anemia

Updated October 3, 2019

This article was scientifically reviewed by Aishwarya Arjunan

We take the information we share seriously. Review our Editorial Policy Here.

A list of references is also included at the bottom of this article.

Sickle Cell Anemia or Sickle Cell Disease (SCD), is a genetic condition that affects the red blood cells and the ability to deliver oxygen to cells in the body.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic. Read More...

Over 100,000 people in the United States are affected with SCD 1.

At YourDNA, we want you to have the information you need to know to manage your condition at your fingertips.

What is Sickle Cell Disease?

Sickle Cell Disease is a genetic condition that results in the formation of abnormal red blood cells.

Red blood cells are made up of a molecule called hemoglobin which is responsible for oxygen transport from our lungs to the rest of the body

Normal blood cells are made up of hemoglobin A and these red blood cells are round in shape and can easily move through the blood vessels 2 3.

The red blood cells in individuals with sickle cell disease primarily contain abnormal hemoglobin that causes them to be misshapen.

These red blood cells are hard, sticky, and crescent “sickle” shaped and do not flow through the blood vessels as smoothly as normal red blood cells disrupting the blood flow.

Additionally, these sickled red blood cells also die prematurely which leads to the anemia that is a classic symptom of the condition.

Sickle cell disease is caused by mutations in the HBB gene 4. The hemoglobin molecule is made up of four protein subunits: two alpha globin subunits and two beta globin subunits.

The HBB gene is responsible for providing the instructions to make beta globin.

Mutations that cause abnormalities with the structure of the beta globin protein structure are responsible for sickle cell disease.

Hemoglobin S is the most common abnormal hemoglobin unit that is associated with sickle cell disease.

Mutations in HBB that cause a reduction in the amount of beta globin produced result in a different condition called beta thalassemia.

Individuals with at least one abnormal hemoglobin S unit in conjunction with a second pathogenic HBB mutation are considered to have sickle cell disease.

The types of sickle cell disease include 5:

  1. Hemoglobin Sβ0 thalassemia
  2.  Hemoglobin Sβ+ thalassemia
  3.  Hemoglobin SC
  4.  Hemoglobin SD
  5.  Hemoglobin SE
  6.  Hemoglobin SS

Collectively, disorders affecting hemoglobin are called hemoglobinopathies.

Since SCD impacts the flow of red blood cells throughout the entire body, the condition impacts many different systems of the body.

A hallmark symptom associated with the condition is anemia and chronic pain.

How Common is Sickle Cell Disease?

While sickle cell disease can be seen in individuals of all ethnic backgrounds, males and females, it is common in individuals of African, Mediterranean, Middle Eastern, Indian, Caribbean descent and in some regions of Central and South American.

Approximately 1 in 10 African Americans in the United States is a carrier for sickle cell disease also known as having sickle cell trait 6.

In the United States, 1 in every 1,1100 African American newborns is affected by SCD 7. According to the National Institutes of Health, over 100,000 people in the United States and 20 million people worldwide have sickle cell disease.

Typically, the condition is diagnosed shortly after birth as all newborns in the United States are screened for this condition along with a number of others within a few days of birth.

What Are the Symptoms of Sickle Cell Disease?

While SCD is present from birth, most newborns do not have any immediate complications. The severity of the symptoms of SCD varies from person to person.

Early symptoms of SCD are jaundice (yellowing of the skin), fatigue, delayed growth, and swelling of the hands and feet (dactylitis) 8.

Anemia

A hallmark complication with SCD is anemia due to the premature death of red blood cells.

The average lifespan of sickled red blood cell is 10-20 days compared to normal red blood cells with a lifespan of 120 days.

Without enough red blood cells, the body does not receive the oxygen it needs to produce energy causing fatigue 9.

Chronic Pain

Pain crisis is the most common complication of sickle cell disease and the primary reason individuals with SCD go to the hospital or emergency room.

Pain occurs when the sickled blood cells clump together and block blood flow through the vessels.

This pain can occur anywhere in the body, vary in intensity and last for a few hours to a few weeks.

While some individuals may only have a few pain episodes, others may experience a dozen or more a year 10 11.

Some preventive measures an individual can take includes ensuring adequate hydration, monitoring temperatures, limit exposure to high altitudes and taking a medicine called hydroxyurea.

Acute Chest Syndrome

Acute chest syndrome (ACS) can occur due to a lung infection or due to sickled cells blocking blood flow in the lung.

Patients with acute chest syndrome may present with chest pain, coughing, difficulty breathing and a fever 12.

Frequent Infections

The sickled red blood cells can damage the spleen which is the organ that is responsible for fighting infections 13.

When the spleen does not work properly, the immune system is impaired and can leave sickle cell patients at higher risk for infections.

Regular vaccinations, good hand hygiene, careful preparation of food and prophylactic antibiotics can help prevent life-threatening infections.

Splenic sequestration occurs when blood is trapped in the vessels of the spleen and causes the spleen to enlarge (splenomegaly) 14 15 16.

This can be a life-threatening complication of SCD. Regular blood transfusions may be used to help prevent this complication.

A splenectomy (or spleen removal) is considered if an individual has more than one episode of splenic sequestration.

Vision Problems

When the blood vessels leading to the eye get clogged by sickled cells, it can restrict blood flow to the eye and damage the retina 17.

Strokes

Strokes can occur if sickled cells block the blood flow to the brain.

Seizures, weakness of arms and legs, sudden speech difficulties and loss of consciousness are all signs of a stroke 18.

Approximately 10% of children with sickle cell anemia will have a stroke and can be fatal.

Pulmonary hypertension

Individuals with SCD can be at risk for developing high blood pressure in their lungs.

This is usually seen in adults and can be fatal. Shortness of breath and fatigue are symptoms associated with this complication 19.

Priapism

Males with SCD can have painful, unwanted, prolonged erections.

It occurs when blood flow from the penis is blocked by sickled cells.

It can cause permanent damage and potentially lead to impotence 20.

Deep Vein Thrombosis

Another serious complication of SCDis the development of a deep vein thrombosis or pulmonary embolism.

This is a blood clot within the deep veins which can lead to disability and even death.

Prevention includes close monitoring and taking medications such as heparin or warfarin, which thin out the blood and make it flow easier.

Pregnancy Complications

Pregnancy complications can occur in females with SCD who become pregnant.

They are at increased risk for high blood pressure and blood clots and SCD increases the risk for miscarriage, premature birth, and low birth weight in babies 21.

Other complications

Individuals with SCD can also experience gallstones, joint complications, kidney and liver problems, and leg ulcers 22.

How is Sickle Cell Disease diagnosed?

In the United States, diagnosis of sickle cell disease will generally come via newborn screening from a physician, generally a pediatrician or medical geneticist.

Hemoglobinopathies are included in every state’s newborn screening and measures the amount of normal hemoglobin present 23.

If low levels of hemoglobin are found then the test is repeated. If the repeat is also abnormal then a referral to a specialist is recommended.

It is important to remember that newborn screening is not diagnostic but will help identify babies that are at increased risk of having sickle cell disease and alert the pediatrician that additional diagnostic testing is necessary.

Diagnostic testing for sickle cell disease is completed by hemoglobin electrophoresis on a blood sample 24.

The hemoglobin electrophoresis will determine the specific type of abnormal hemoglobin present and the level at which it exists in the bloodstream.

If an individual is believed to have sickle cell disease then additional genetic testing is completed.

While carriers of sickle cell disease (also known as having sickle cell trait) are not affected with the condition, they will also have some amount of sickled cells present in the blood.

However, individuals with sickle cell trait have an adequate amount of normal red blood cells to compensate for the sickled ones and avoid complications associated with sickle cell disease.

Genetic Testing

Genetic testing for sickle cell disease is completed by obtaining a blood sample from the patient and sending for HBB analysis.

The test will look to see if there are any disease causing mutations in the HBB gene.

The presence of at least one Hemoglobin S causing mutation and another disease causing mutation in the HBB gene will help confirm the diagnosis of sickle cell disease.

How is sickle cell disease treated?

Sickle cell disease is a chronic, lifelong condition that requires ongoing monitoring and management by a specialist.

Most individuals with sickle cell disease are part of special sickle cell disease programs.

Bone marrow and stem cell transplants are the only therapies currently available to potentially cure sickle cell disease but are not an option for the vast majority of individuals with the disease because they are not able to identify suitable stem cell donors 25.

Generally, treatment for sickle cell disease is limited to symptom management and preventive measures.

Treatment options include childhood vaccinations, antibiotics, pain management, blood transfusions and hydroxyurea.

Monitoring

Certain blood tests may be performed to monitor the health of individuals with sickle cell disease.

Testing bilirubin levels can monitor and lower risk of developing gallstones and serum creatinine levels can help evaluate kidney function.

Blood oxygen levels, complete blood counts (CBCs) and serum potassium levels may also be checked to monitor and evaluate function 26.

Vaccinations

In order to reduce the risk of infections, people with SCD are encouraged to take prophylactic antibiotics and stay up to date on their vaccinations

Antibiotics such as penicillin are recommended along with the Haemophilus influenzae vaccine (Hib), Pneumococcal conjugate vaccine (PCV) and the Pneumococcal polysaccharide vaccine (PPSV) 27.

Pneumonia is a severe complication in young children and infants with sickle cell disease so along with prophylactic antibiotics and vaccinations, it is important for families to take precautions such as good hand hygiene.

Pain Management

The chronic pain associated with sickle cell disease can lead to many hospitalizations and is often managed by a combination of blood transfusions, pain medications and fluids.

Over the counter pain medication may be used to alleviate some pain but generally the pain experienced by sickle cell patients requires stronger pain medication that can only be administered in the hospital. Bloo

Transfusions

Depending on a patient’s symptoms, blood transfusions can help provide normal red blood cells allowing for more hemoglobin to flow freely in the body and deliver oxygen as needed.

These transfusions can help alleviate some of the symptoms associated with the condition as the transfused red blood cells will live longer in the body than the sickled red blood cells 28.

Risks of transfusions include iron overload in which excess iron from the transfused red blood cells build up and can cause damage to various organs.

Individuals with frequent blood transfusions may need to take medicine (chelation therapy) to remove the excess iron from their body 29.

The immune system of some individuals also react adversely to transfusions and may prevent individuals from receiving transfusions in the future 30.

And albeit rare, there is always the possibility of transmission of infections.

Hydroxyurea

Hydroxyurea is a medicine that stimulates the production of fetal hemoglobin (Hb F) which is generally only found in newborns.

Fetal hemoglobin help prevent red blood cells from sickling and has shown to reduce the complications associated with the condition.

Studies have shown that hydroxyurea can help lower sickle cell pain crises events, number of acute chest syndrome events and the number of blood transfusions.

Many sickle cell patients prefer taking hydroxyurea daily instead of having regular blood transfusions 31.

Bone Marrow Transplants

The only way to cure sickle cell disease is through bone marrow transplant/stem cell transplant.

During this transplant, a sickle cell patient will have their bone marrow replaced with a normal bone marrow.

However, finding a compatible matched donor is difficult and these transplants are not a viable option for many sickle cell patients 32.

Transplants also carry the risk for severe side effects that can potentially lead to death.

Because of these risks and limited availability of well-matched donors, it’s only performed in very severe cases of sickle cell disease where patients have organ damage, stroke or frequent pain crises.

Other treatment options

Some patients with sickle cell disease may also have surgery to remove the gallbladder, wound care to address leg ulcers, kidney dialysis or transplant therapies due to kidney disease, hip replacement surgery due to avascular necrosis of the hip (death of hip bone due to poor blood supply) and/or laser surgery to address vision problems 33.

What is the life expectancy of an individual with sickle cell disease?

While treatment for sickle cell disease has improved over the past decades, individuals with the condition have a reduced life expectancy of 42-47 years 34.

It is important to remember that individuals with sickle cell disease experience a variety of different symptoms with some having a more severe disease progression than others so the prognosis can be quite different depending on the severity of the condition.

How is Sickle Cell Disease Inherited?

Sickle Cell Disease is inherited in an autosomal recessive pattern. This means that people with sickle cell disease have inherited two copies of the defective (or mutated) SCD gene, one copy from each parent.

We have 46 chromosomes in each cell of our bodies. These chromosomes can be organized into 23 pairs.

One of each pair of chromosomes is inherited from each parent. Our genetic information, or our genes, is carried on the chromosomes.

Genes are instructions telling our bodies how to grow and develop.

While each person has two working copies of each gene, parents of children with cystic fibrosis will have one copy that has a mutation and one copy that is working without any problems.

Because they have one working copy of the gene, they do not have any signs or symptoms of SCD.

This is called “autosomal recessive inheritance”. Parents who have one copy with a gene mutation are called “carriers”.

For sickle cell disease specifically, carriers are referred to as having “sickle cell trait”.

As mentioned above, having sickle cell trait does not mean that one is affected with the condition.

However, because they have sickle cell trait, these individuals will also have some amount of sickled cells present in the blood.

However, individuals with sickle cell trait have an adequate amount of normal red blood cells to compensate for the sickled ones and avoid complications associated with sickle cell disease.

Credit: U.S. National Library of Medicine

SCD occurs when an individual inherits two mutations in the HBB gene.

When two parents with sickle cell trait have a child who inherits both copies with a gene mutation, one from each parent, the child will have SCD.

What are the chances that I will pass sickle cell disease to my child?

  • If neither parent has a disease causing gene mutation; that is, neither parent is a carrier, then it is highly unlikely that sickle cell disease will be passed down.
  • If only one parent has sickle cell trait, is a carrier for SCD, and the other parent has two normal working copies of the HBB gene, the children of that couple will each have a 50 percent chance (1/2) of having sickle cell trait like one of their parents.
  • If both parents have sickle cell trait, then there is a 1 in 4 or 25% chance in each pregnancy to have a child with SCD. This also means that there is a 3 in 4 or 75% chance in each pregnancy to not have a child with SCD.

Genetic Testing for Sickle Cell Disease

Blood testing via hemoglobin electrophoresis followed by genetic testing looking for disease causing mutations in the HBB gene can help establish a diagnosis of sickle cell disease.

Speak with your health care provider if you wish to learn more about genetic testing for sickle cell disease.

A referral to a genetic counselor can be helpful to discuss the various testing options for you and your family.

Is prenatal testing available?

Genetics play a very critical part in whether a person develops the disorder, or even if they are a carrier who can pass it onto their children.

If parents want to know their risk of having a child with sickle cell disease then they can consider getting carrier screening prior to or in the early stages of pregnancy.

Carrier screening will help identify whether an individual or couple are both carriers for cystic fibrosis and thus at risk of having a child with the condition.

If a couple is identified to both have sickle cell trait, then prenatal diagnosis via chorionic villus sampling (CVS) or amniocentesis can help determine whether the fetus is affected.

If carrier screening is done prior to pregnancy and a couple is identified to both be carriers for cystic fibrosis then that couple can explore other options such as pre-implantation genetic testing with IVF, using an egg or sperm donor, or adoption.

Speaking with a health care provider like a genetic counselor to help determine if this testing is right for you.

Where can I go to get genetic testing?

If you’re interested in getting genetic testing done, it’s recommended that you discuss options with your pediatrician or primary care physician

When considering any form of genetic testing, it can be helpful to speak with your healthcare provider to learn about the benefits and limitations of testing and testing options.

It is always advised to complete diagnostic testing under the guidance of a healthcare provider.

DNA Testing for Sickle Cell Disease: Strengths and Limitations

Genetic testing can a mix of benefits and limitations. There is no possibility of physical harm or any biological risk in getting tested aside from the general risk of a blood draw if a blood draw is completed.

Although deciding on testing is entirely voluntary, it can prove to be a complex decision that may raise new health concerns or anxieties.

For this reason, it’s best to seek genetic counseling to help discuss the emotional and social aspects of genetic testing, as well as get an educated interpretation of the results.

With that in mind, here is a short list of the strengths and limitations:

Benefits of Genetic Testing:

  1. Relief from any uncertainty about whether or not SCD is the appropriate diagnosis.
  2. In-depth understanding about the disease and how it impacts you and your health.
  3. You will be in a position to educate your family about the potential risk of passing down the condition or help diagnose other family members who may also have SCD.
  4. Knowing you are a carrier can help you make future family-planning decisions.

Limitations of DNA Testing:

  1. Your new knowledge will not lead to a cure, but will help empower you to make decisions about your health and future
  2. You may not be able to get a conclusive answer after genetic testing which may then lead to a feeling of uncertainty about the diagnosis and family planning.

Powered by Froala Editor

Referenced Sources

  1. Bender MA. Sickle Cell Disease. 2003 Sep 15, Updated 2017 Aug 17. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2019.
  2. Sickle Cell Disease. Genetics Home Reference, US National Library of Medicine. Retrieved Online August 2019.
  3. Sickle Cell Disease Association of America. Retrieved Online August 2019.
  4. Sickle Cell Disease. Genetics Home Reference, US National Library of Medicine. Retrieved Online August 2019.
  5. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  6. Bender MA. Sickle Cell Disease. 2003 Sep 15, Updated 2017 Aug 17. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2019.
  7. Bender MA. Sickle Cell Disease. 2003 Sep 15, Updated 2017 Aug 17. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2019.
  8. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  9. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  10. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  11. Sickle Cell Anemia. Mayo Clinic. Retrieved Online August 2019.
  12. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  13. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  14. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  15. Sickle Cell Anemia. Mayo Clinic. Retrieved Online August 2019.
  16. Splenic Sequestration. Indiana Hemophilia and Thrombosis Center. Retrieved Online August 2019.
  17. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  18. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  19. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  20. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  21. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  22. Sickle Cell Disease. National Heart, Lung, and Blood Institute. Retrieved Online August 2019.
  23. Sickle Cell Disease. STAR-G: Screening Technologies and Research in Genetics. Newbornscreening.info Retrieved online August 2019.
  24. Adult Sickle Cell Disease. University of Pittsburgh Medical Center. Retrieved Online August 2019.
  25. Adult Sickle Cell Disease. University of Pittsburgh Medical Center. Retrieved Online August 2019.
  26. Adult Sickle Cell Disease. University of Pittsburgh Medical Center. Retrieved Online August 2019.
  27. Adult Sickle Cell Disease. University of Pittsburgh Medical Center. Retrieved Online August 2019.
  28. Red Blood Cell Transfusions for Sickle Cell Disease. St Jude Children’s Research Hospital. Retrieved Online August 2019.
  29. Red Blood Cell Transfusions for Sickle Cell Disease. St Jude Children’s Research Hospital. Retrieved Online August 2019.
  30. Red Blood Cell Transfusions for Sickle Cell Disease. St Jude Children’s Research Hospital. Retrieved Online August 2019.
  31. Hydroxyurea Treatment for Sickle Cell Disease. St Jude Children’s Research Hospital. Retrieved Online August 2019.
  32. Hydroxyurea Treatment for Sickle Cell Disease. St Jude Children’s Research Hospital. Retrieved Online August 2019.
  33. Adult Sickle Cell Disease. University of Pittsburgh Medical Center. Retrieved Online August 2019.
  34. Case Study: Rare Patients With Sickle Cell Disease Live Nearly Twice as Long as National Average. American Society of Hematology. Retrieved Online August 2019.