Why Are There Different Types Of Sickle Cell?

“Sickle cell disease” is an umbrella term used to describe a group of genetic diseases that affect the body’s hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen. It is made up of 2 alpha-globin chains and 2 beta-globin chains. Sickle cell disease is caused by a mutation in the beta-globin gene, resulting in abnormal hemoglobin called sickle hemoglobin or Hb S. Different types of sickle cell disease arise based on whether the hemoglobin beta S gene is inherited with another beta S gene or with a different beta gene mutation.

 

The Main Types Of Sickle Cell Disease:

Hemoglobin SS Disease

Hemoglobin SS disease is the most common and most severe type of sickle cell disease. It occurs when you inherit the hemoglobin S gene mutation from both parents. In this type, the body only produces hemoglobin S. This type is often called “sickle cell anemia.”

Hemoglobin SB 0 (Beta Zero) Thalassemia

Hemoglobin S beta zero thalassemias occur when you inherit the hemoglobin beta S gene from one parent and a hemoglobin beta0 thalassemia gene mutation from the other parent. It has similar symptoms to hemoglobin SS disease and is also called sickle cell anemia because the body only produces hemoglobin S.

Hemoglobin SC Disease

Hemoglobin SC disease is the second most common type of sickle cell disease. It occurs when you inherit the hemoglobin beta S gene from one parent and the hemoglobin C gene from the other. Individuals with hemoglobin SC disease may have similar symptoms to individuals with hemoglobin SS disease. However, the symptoms may be less severe.

Hemoglobin SB+ (Beta) Thalassemia

Hemoglobin SB+ (beta) thalassemia occurs when you inherit the hemoglobin beta S gene from one parent and a hemoglobin beta plus thalassemia gene from the other parent. In this type, some normal beta hemoglobin is produced, but in reduced amounts. Because the body produces some normal hemoglobin, this form of sickle cell disease is less severe than hemoglobin SS disease. Symptoms are usually milder than hemoglobin SS or SC disease, but complications can still develop.

Hemoglobin SD, Hemoglobin SE, And Hemoglobin SO

These types of sickle cell disease are less common and are usually less severe.

Hemoglobin SD, Hemoglobin SE, và Hemoglobin SO

What Happens In Sickle Cell?

The root cause of sickle cell starts with a process called hemoglobin polymerization. This process changes the shape of red blood cells and impacts their ability to carry oxygen throughout the body.

Why Do Red Blood Cells Form A Sickle Shape?

Red blood cells contain a protein called hemoglobin. Hemoglobin carries the oxygen that blood delivers throughout the body.

·         When the hemoglobin molecules are carrying oxygen, they move around the blood cell freely

·         In the sickle cell, after hemoglobin has delivered oxygen to tissues, the red blood cell does not keep its round shape

·         When hemoglobin lose their oxygen, they start to stick together and form long, stiff chains (called polymers) inside the cell

·         Because these chains of hemoglobin keep building, they can get longer than the red blood cell itself and curve its shape into the sickle or crescent shape.

 

Hemoglobin Polymerization

When you have sickle cell disease, red blood cells are sickling and continue to cause damage and injury even when you do not feel any pain. The silent damage of sickle cell is caused by these three things:

·         Hemolysis – The fast breakdown of red blood cells

·         Anemia – Having too few healthy red blood cells to carry oxygen to the body’s tissues

·         Vaso-occlusion – Blockage of blood vessels by sickled red blood cells, which can lead to pain crises and organ damage

Recently, researchers have learned a lot more about these changes and what causes them.

How Long Do Red Blood Cells Live?

Sickled red blood cells don’t live as long as healthy red blood cells do. Here’s the difference:

• Healthy red blood cells live about 120 days. They are always traveling through the body and picking up oxygen from the lungs. Then they deliver it throughout the body
• Sickled red blood cells live for only about 10 to 20 days. That’s because sickled red blood cells are more fragile than healthy round red blood cells

How Hemolysis Affects Your Body:

-Every part of the body needs oxygen. The job of hemoglobin is to make sure that the body gets that oxygen. Hemoglobin is the part of the red blood cell that carries oxygen to all parts of the body

-Sickled red blood cells break down faster than they should

-When blood cells break down faster, there are fewer red blood cells (and the hemoglobin inside them) that are working the way they should

-Fewer red blood cells lead to anemia. Anemia is when your blood is not able to carry enough oxygen throughout your body. The result is that the body doesn’t get all of the oxygen it needs

-Over time, hemolysis, anemia, and vaso-occlusion can lead to chronic damage to tissues, organs, and bones.

 Anemia

Anemia is a condition that occurs in your body when you don’t have enough healthy red blood cells or hemoglobin to carry enough oxygen to your body’s tissues. This can be a problem because all of your tissues need oxygen to survive.

In the sickle cell, anemia occurs as a result of hemolysis. Sickled red blood cells break down faster than the body can make new ones. When there aren’t enough red blood cells, there isn’t enough oxygen. Not getting enough oxygen to your organs and tissues may lead to silent damage and long-term complications that we sometimes don’t think about or notice.

Having anemia puts a lot of stress on the heart and blood vessels. They need to work harder than usual to pump blood to provide oxygen to the body.

How Anemia Affects The Body

Anemia can lead to several short-term issues, including:

• Fatigue
• Weakness
• Less ability to do physical things
• Difficulty thinking and concentrating
• Jaundice (yellowing of the skin and eyes)

 Anemia’s Link To Silent Damage

When somebody experiences anemia over a long period of time, it can also lead to silent damage to organs, including the:

·         Brain (which can lead to stroke)

·         Eyes

·         Heart and lungs

·         Liver and gallbladder

·         Spleen

·         Kidneys

·         Bones

·         Other organs

The Importance Of Labs And Screenings

At your routine clinic or doctor visit, your labs are checked for:

·         Hemoglobin

·         Red blood cell counts

·         Reticulocytes (also called “relics,” these are new or “baby” blood cells)

This information can tell you and your healthcare professional if you are making too few red blood cells, if too many of them are breaking down quickly, or any other changes that could lead to silent damage.

Additional screening recommendations that you can ask your doctor about include:

·         Renal disease, which is a disease of the kidneys

·         Hypertension also called high blood pressure

·         Retinopathy, which is damage to the retina of the eyes and can lead to vision impairment

·         Stroke, which is caused by a sudden interruption of the blood supply to the brain

·         Pulmonary Disease, which refers to any disease that affects the lungs or respiratory system

Vaso-Occlusion

One of the complications of sickle cell is vaso-occlusion.

The breakdown of vaso-occlusion:

• Vaso = Blood vessels
• Occlusion = Blocked up

So, vaso-occlusion means that blood vessels become blocked up.

In people with sickle cell, blood vessels get blocked by sickled red blood cells because they have trouble flowing smoothly through the vessels. Instead, they pile up and block the blood vessels. When blood vessels are blocked, the flow of blood is reduced and tissues don’t get the oxygen they need.

 

Vaso-occlusion can cause:

• In the short-term: pain. That’s the pain that people with sickle cells know so well and suffer from so much. The pain can come on suddenly or build up over a few days. This pain is known as a pain crisis. It can resolve in a few days.
• In the long-term, vaso-occlusion along with hemolysis and anemia can cause silent damage. Silent damage to your tissue, organs, and bones can continue even after the pain goes away, leading to long-term complications.

Sickled Cells Causing A Blockage In A Blood Vessel

 Sickle Cell Is An Inherited Genetic Condition

Having sickle cell trait doesn’t mean that you have sickle cell disease. People with sickle cell trait have inherited a sickle cell gene from one parent and a normal gene from the other parent. In order to have sickle cell disease, a person must inherit two sickle cell genes, one from each parent.

 

A person who inherits the sickle cell gene from only one parent is called a trait carrier. A trait carrier is healthy but can pass the sickle gene to their children. Some people who carry the sickle cell trait don’t even know they have it. Most people with sickle cell trait will not have any symptoms or complications and will not know they have sickle cell trait unless they are tested for it. In order to have sickle cell disease, a person must inherit two sickle cell genes, one from each parent.

 What Health Problems Might Occur In People With Sickle Cell Trait?

Most people with sickle cell trait do not have any health problems caused by the trait. However, there are a few, rare health problems that may be related to sickle cell trait. One example is a pain when traveling to or exercising at high altitudes. People with sickle cell trait should tell their doctor when something like this happens or if they notice blood in their urine or get an eye injury even if it doesn’t seem that bad.

 

People with sickle cell trait should drink plenty of water during exercise. All people with sickle cell trait should be careful when doing strenuous exercise. Before starting an exercise program talk with your doctor.

 

Inheriting The Genes For Sickle Cell Disease And Sickle Cell Trait

 

If each parent has one normal hemoglobin gene and one sickle cell hemoglobin gene. This means each of their children has:

• A 25% chance of inheriting two normal hemoglobin genes, and not having sickle cell trait or disease
• A 50% chance of inheriting one normal hemoglobin gene and one sickle cell hemoglobin gene, and carrying the sickle cell trait
• A 25% chance of inheriting two sickle cell hemoglobin genes, and having sickle cell disease

Each time this couple has a child, the chances of that child having sickle cell disease remain the same. In other words, if their first child is born with sickle cell disease, there is still a 25% chance that their second child will also have sickle cell disease.

If a person wants to know if they carry a gene for sickle cell, a doctor can order a blood test to find out.

 

Getting Tested For Sickle Cell Is Easy

 

Early diagnosis of sickle cells is very important because many complications can be prevented with early diagnosis and treatment. Sickle cell disease and sickle cell trait are both diagnosed with a simple blood test.

In 2006 it became mandatory to test all newborns for sickle cell in the United States. But older children and adults can be tested, too. If you were born before 2006 or if you don’t know if you were tested, you can ask your doctor for a blood test.

If the screening test is positive, more tests are needed to tell whether the person is a carrier for the sickle cell trait or, if the person has sickle cell disease, what type they have.

 

It’s also possible for doctors to diagnose sickle cell before birth. This is done by sampling some of the fluid surrounding the baby in the mother’s womb (amniotic fluid) or tissue taken from the placenta. This test can be done in the first few weeks of pregnancy if you know or think you may carry the gene. A woman can ask for a referral to a genetic counselor who can help her understand the risk to her baby.

 Additional Tests.

 

If a baby is born with sickle cell, they may not show symptoms until about 6 months after birth. At the first doctor’s visit, the doctor will typically do a blood test to establish their normal hemoglobin level. Additional blood tests may occur at future visits to check hemoglobin levels and make sure that the red blood cell count is not too low (anemia). A doctor might also suggest additional tests to check for possible complications of the condition. If your doctor does not do these tests, ask for them.

 

Sickle Cell Symptoms Can Change Throughout Life

 

Sickle cell is present from the start of life—you are born with it. It’s hard to know how it will behave in newborns. Infants usually don’t have symptoms in the first few months of life because the fetal hemoglobin produced before birth protects the red blood cells from sickling. A baby may start to have symptoms by 6 months of age. If you notice any symptoms, be sure to discuss them with your doctor.

 

Symptoms In Babies & Toddlers:

-A yellowish color of the skin (jaundice) or whites of the eyes (icterus), which occurs when a large number of red blood cells break apart
-Fatigue or fussiness because of anemia
-Painful swelling of the hands and feet (dactylitis)
-Not making enough red blood cells (anemia)

-Blood getting trapped in the spleen (acute splenic sequestration)

-Frequent infections

Most of the symptoms of sickle cell are related to complications of the disease. Some, such as fatigue, anemia, pain episodes, and bone problems, can occur at any age.

 

Symptoms In Teens & Young Adults

 

Teens and young adults may develop leg ulcers, avascular necrosis (death of bone tissue due to lack of blood supply), acute chest syndrome, and eye damage.

 

Symptoms In Adults

 

Adults generally have pain crises caused by an injury to a bone, muscle or internal organs.

Listen To Your Body So You Can Manage Your Symptoms

To manage sickle cell day to day, it’s a good idea to:

• Become aware of your body. Don’t dismiss what it’s trying to tell you
• Be alert for warning signs
• Talk with your healthcare provider about your symptoms. Seeking treatment early can keep symptoms from turning into complications

 

Some common symptoms you might have to manage with your sickle cell include:

 

Anemia

Anemia is having too few healthy red blood cells. That means that your blood can’t carry enough oxygen. People with sickle cell usually have mild to moderate anemia. But at times they can have severe anemia, which can be life-threatening.

 

Infection

People with sickle cell, especially infants and children, are more likely to get infections. These infections can include:

• The flu (influenza)
• Infection in the brain or spinal cord (meningitis)
• Infection in the liver (hepatitis)

 

Hand-Foot Syndrome

When sickled cells get stuck in the blood vessels, it blocks blood flow to the arms and legs. That causes swelling in the hands and feet. Fever may occur as well. This most often happens in children under 6 years old. About half of children with sickle cell will have this.

 

Eye Problems

Sickle cell can affect the blood vessels in the eyes. That can lead to long-term damage, including loss of vision. The retina is the place where damage usually occurs. The retina is the part of the eye that senses light and sends visual messages to the brain. When it is not working blindness can result.

 

Leg Ulcers

Sickle cell ulcers are sores that usually start small and then get bigger.

Some ulcers will heal quickly, and others may take longer to heal. Some ulcers come back even after they’ve healed. These ulcers usually start after the age of 10 years.

 

Joint Complications

Sickle cell can block blood vessels leading to the joints. That means that less blood goes to the hips, shoulders, knees and ankles, which might cause damage.

Symptoms include pain and problems with walking and joint movement.

 

Delayed Growth And Puberty

Because of their anemia, children with sickle cell may grow and develop at a slower pace than other children, and they may take longer to reach puberty.

 

The Silent Damage

 

Although pain is the most common symptom, sickle cell is much more than pain. Sickled red blood cells don’t deliver oxygen to your body’s organs, tissues, and bones as well as healthy red blood cells do. And your organs need oxygen. There may be gradual damage that happens to your body’s organs, tissues, or bones that you might not see or feel. This damage can add up over time and may occur even if you don’t have a pain crisis. It can also occur long after a pain crisis has passed. That’s the silent damage of the sickle cells.

 

What Is The Impact Of Silent Damage?

 

With sickle cell, damage may be happening to your body whether or not you have pain. And it’s all because your red blood cells are not delivering enough oxygen to your body. Without oxygen, any organ in your body can be affected over time. That includes your:

• Brain
• Eyes
• Heart and lungs
• Liver and gallbladder
• Spleen
• Kidneys
• Bones
• Other organs

Over time, these effects can build up and cause illness, serious complications, and even shortened lifespan.

 

What Can I Do To Detect Silent Damage?

Screening for silent damage is one way you and your doctor can be proactive in your healthcare. Screening tests are tests that detect changes or worsening of changes, as early as possible. Ask your healthcare provider what types of screenings are recommended for you and when you should do them.

 

 Understand The Risks Of Sickle Cell

 

Talk with your healthcare provider about the risks of sickle cell. It’s not easy, but it’s important to know about it. Talk about the changes you notice in your body and any concerns you have. The problems of the sickle cell can be scary, painful, and dangerous. Understanding them is the first step to being proactive in your health and taking action. In addition to understanding the complications, you can also learn how to manage the experiences you might face.

 

Some of the most common problems that come with sickle cell include:

 

Pain

Pain is a common problem with sickle cell. You should talk to your doctor about any pain you’re having. You might have pain in your back, knees, legs, arms, chest, or stomach. The pain can be throbbing, sharp, dull or stabbing. How often and how bad the pain gets varies from person to person. You may have pain that’s just always there but doesn’t hurt as badly. You may also have severe pain that starts suddenly and lasts for several hours. That’s called a pain episode, or a pain crisis. A pain crisis happens when sickled red blood cells block blood vessels that carry blood to your bones and organs. Possible pain triggers include:

·         Stress

·         Not drinking enough fluids

·         Illness

·         Changes in temperature

·         Being at high altitudes (like in the mountains)

 

Acute Chest Syndrome

Blockage of blood flow to the lungs can cause acute chest syndrome (ACS). When this happens, areas of lung tissue are damaged and can’t provide oxygen. It can be life-threatening and should be treated in a hospital. ACS often starts a few days after a pain crisis starts. Symptoms may include:

• Chest pain
• Cough
• Fever
• Rapid breathing
• Shortness of breath

Talk to your doctor if you experience these symptoms.

 

Stroke

A stroke happens when blood flow is blocked to a part of the brain. When this happens, brain cells can be damaged or can die. The symptoms depend on what part of the brain is affected. Symptoms of a stroke may include:

·         Loss of balance

·         Severe headache

·         Trouble speaking, walking or understanding

·         A weakness of an arm or leg on one side of the body

Talk to your doctor if you experience these symptoms.

 

Silent Stroke Or Learning Disabilities

Silent brain injury is damage to the brain with no outward signs of a stroke. Brain imaging and tests of thinking have shown that children and adults with sickle cell often have signs of silent brain injury, also called the silent stroke.

Be sure to talk to your doctor if you think you have experienced a silent stroke or experience learning difficulties.

 

Heart Problems

People with sickle cell can have problems with blood vessels in the heart and their heart can become larger than normal. They can also have a type of high blood pressure known as pulmonary hypertension, which happens in the blood vessels of the lungs and heart. Pulmonary hypertension can cause shortness of breath and fatigue. People with sickle cell who have had a lot of blood transfusions may also have heart damage because they’ve received too much iron.

Talk to your doctor if you experience these symptoms or if you are concerned about blood transfusions.

 

Kidney Problems

Sickled red blood cells are hard on the kidneys. People with sickle cell can have:

·         Urine that is not as concentrated as it should be

·         Frequent urinating

·         Bedwetting

·         Blood in the urine

·         Protein in the urine

It’s always important to drink plenty of water. Talk with your healthcare provider about any trouble that you’re having with urination.

 

Priapism

Males with sickle cell can have unwanted and painful erections that last a long time. This condition is called priapism. Priapism happens when blood flow out of the erect penis is blocked by sickled cells. If it goes on for a long time without medical help, priapism can cause permanent damage to the penis and lead to impotence. Get medical care if priapism lasts for more than 4 hours.

 

Gallstones

When red blood cells die, they release hemoglobin into the bloodstream. Hemoglobin breaks down into a substance called bilirubin. Bilirubin can form stones that get stuck in the gallbladder. The gallbladder is a small, sac-shaped organ beneath the liver that helps with digestion. Many people with sickle cell have gallbladder problems. Gallstones can also lead to gallbladder infection. Symptoms of gallbladder problems include:

• Nausea
• Pain in the right upper belly (especially after eating fatty foods)
• Vomiting

Talk to your doctor if you experience these symptoms.

 

Liver Complications

When sickled cells block blood vessels in the liver, it can prevent oxygen from reaching liver tissue. These episodes are usually sudden and can happen repeatedly. Children often recover, but some adults may have ongoing problems that lead to liver failure. People with sickle cell who have received frequent blood transfusions may develop liver damage from iron overload.

Talk to your doctor if you think you may have liver complications.

 

Complications In Pregnancy

Pregnancies in women with sickle cell can be risky for both mother and baby.

During pregnancy, women may have medical problems that include:

·         Blood clots

·         High blood pressure

·         Increased pain episodes

·         Infections

They also are at higher risk for:

• Miscarriages
• Premature births
• Small-for-date or underweight babies