Sickle Cell Anemia and its Prevention
Published on Sep 05, 2023
Sickle cell anemia is the most common form of sickle cell disease (SCD). SCD is a serious disorder in which the body makes sickle-shaped red blood cells. “Sickle-shaped” means that the red blood cells are shaped like a crescent.
Normal red blood cells are disc-shaped and look like doughnuts without holes in the center. They move easily through your blood vessels. Red blood cells contain an iron-rich protein called hemoglobin. This protein carries oxygen from the lungs to the rest of the body.Sickle cells contain abnormal hemoglobin called sickle hemoglobin or hemoglobin S. Sickle hemoglobin causes the cells to develop a sickle, or crescent, shape.
Sickle cells are stiff and sticky. They tend to block blood flow in the blood vessels of the limbs and organs. Blocked blood flow can cause pain and organ damage. It can also raise the risk for infection.
Normal Red Blood Cells and Sickle Cells
Figure A shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin. Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The inset image shows a cross-section of a sickle cell with abnormal (sickle) hemoglobin forming abnormal strands.
Sickle Cell Mutation
Sickle cell anemia has no widely available cure. However, treatments to improve the anemia and lower complications can help with the symptoms and complications of the disease in both children and adults. Blood and marrow stem cell transplants may offer a cure for a small number of people.
Over the past 100 years, doctors have learned a great deal about sickle cell anemia. They know its causes, how it affects the body, and how to treat many of its complications.
Sickle cell anemia varies from person to person. Some people who have the disease have chronic (long-term) pain or fatigue (tiredness). However, with proper care and treatment, many people who have the disease can have improved quality of life and reasonable health much of the time.
Because of improved treatments and care, people who have sickle cell anemia are now living into their forties or fifties, or longer.
What Causes Sickle Cell Anemia?
Sickle cell anemia is an inherited disease. People who have the disease inherit two genes for sickle hemoglobin—one from each parent.
Sickle hemoglobin causes red blood cells to develop a sickle, or crescent, shape. Sickle cells are stiff and sticky. They tend to block blood flow in the blood vessels of the limbs and organs. Blocked blood flow can cause pain and organ damage. It can also raise the risk for infection.
Sickle Cell Trait
People who inherit a sickle hemoglobin gene from one parent and a normal gene from the other parent have sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin.
People who have sickle cell trait usually have few, if any, symptoms and lead normal lives. However, some people may have medical complications.
People who have sickle cell trait can pass the sickle hemoglobin gene to their children. The following image shows an example of an inheritance pattern for sickle cell trait.
Example of an Inheritance Pattern for Sickle Cell Trait
When both parents have a normal gene and an abnormal gene, each child has a 25 percent chance of inheriting two normal genes; a 50 percent chance of inheriting one normal gene and one abnormal
What Are the Signs and Symptoms of Sickle Cell Anemia
The signs and symptoms of sickle cell anemia vary. Some people have mild symptoms. Others have very severe symptoms and often are hospitalized for treatment.Sickle cell anemia is present at birth, but many infants don't show any signs until after 4 months of age.The most common signs and symptoms are linked to anemia and pain. Other signs and symptoms are linked to the disease's complications.
Signs and Symptoms Related to Anemia
The most common symptom of anemia is fatigue (feeling tired or weak). Other signs and symptoms of anemia include:
• Shortness of breath
• Coldness in the hands and feet
• Paler than normal skin or mucous membranes (the tissue that lines your nose, mouth, and other organs and body cavities)
• Jaundice (a yellowish color of the skin or whites of the eyes)
Signs and Symptoms Related to Pain
Sudden pain throughout the body is a common symptom of sickle cell anemia. This pain is called a sickle cell crisis. Sickle cell crises often affect the bones, lungs, abdomen, and joints.
These crises occur when sickled red blood cells block blood flow to the limbs and organs. This can cause pain and organ damage.The pain from sickle cell anemia can be acute or chronic, but acute pain is more common. Acute pain is sudden and can range from mild to very severe. The pain usually lasts from hours to as long as a week or more.Many people who have sickle cell anemia also have chronic pain, especially in their bones. Chronic pain often lasts for weeks or months and can be hard to bear and mentally draining. Chronic pain may limit your daily activities.
Almost all people who have sickle cell anemia have painful crises at some point in their lives. Some have these crises less than once a year. Others may have crises once a month or more. Repeated crises can damage the bones, kidneys, lungs, eyes, heart, and liver. This type of damage happens more often in adults than in children.Many factors can play a role in sickle cell crises. Often, more than one factor is involved and the exact cause isn't known.
You can control some factors. For example, the risk of a sickle cell crisis increases if you're dehydrated (your body doesn't have enough fluids). Drinking plenty of fluids can lower the risk of a painful crisis.You can't control other factors, such as infections.Painful crises are the leading cause of emergency room visits and hospital stays for people who have sickle cell anemia.
Complications of Sickle Cell Anemia
Sickle cell crises can affect many parts of the body and cause many complications.
Sickle cells can block the small blood vessels in the hands and feet in children (usually those younger than 4 years of age). This condition is called hand-foot syndrome. It can lead to pain, swelling, and fever.Swelling often occurs on the back of the hands and feet and moves into the fingers and toes. One or both hands and/or feet might be affected at the same time.
The spleen is an organ in the abdomen. Normally, it filters out abnormal red blood cells and helps fight infections. Sometimes the spleen may trap red blood cells that should be in the bloodstream. This causes the spleen to grow large and leads to anemia.If the spleen traps too many red blood cells, you may need blood transfusionsuntil your body can make more cells and recover.
Both children and adults who have sickle cell anemia may get infections easily and have a hard time fighting them. This is because sickle cell anemia can damage the spleen, an organ that helps fight infections.
Infants and young children who have damaged spleens are more likely to get serious infections that can kill them within hours or days. Bloodstream infections are the most common cause of death in young children who have sickle cell anemia.Medicines and vaccines can help prevent severe illness and death. For example, vaccines are available for infections such as meningitis, influenza, and hepatitis.
Getting treatment right away for high fevers (which can be a sign of a severe infection) also helps prevent death in infants and children who have sickle cell anemia.It's also important to get treatment right away for a cough, problems breathing, bone pain, and headaches.
Acute Chest Syndrome
Acute chest syndrome is a life-threatening condition linked to sickle cell anemia. This syndrome is similar to pneumonia. An infection or sickle cells trapped in the lungs can cause acute chest syndrome.People who have this condition often have chest pain, shortness of breath, and fever. They also often have low oxygen levels and abnormal chest X ray results.
Damage to the small blood vessels in the lungs makes it hard for the heart to pump blood through the lungs. This causes blood pressure in the lungs to rise.Increased blood pressure in the lungs is called pulmonary hypertension (PH). Shortness of breath and fatigue are the main symptoms of PH.
Delayed Growth and Puberty in Children
Children who have sickle cell anemia often grow more slowly than other children. They may reach puberty later. A shortage of red blood cells causes the slow growth rate. Adults who have sickle cell anemia often are slender or smaller in size than other adults.
Two forms of stroke can occur in people who have sickle cell anemia. One form occurs if a blood vessel in the brain is damaged and blocked. This type of stroke occurs more often in children than adults. The other form of stroke occurs if a blood vessel in the brain bursts.Either type of stroke can cause learning problems and lasting brain damage, long-term disability, paralysis (an inability to move), or death.
Sickle cells also can affect the small blood vessels that deliver oxygen-rich blood to the eyes. Sickle cells can block these vessels or cause them to break open and bleed. This can damage the retinas—thin layers of tissue at the back of the eyes. The retinas take the images you see and send them to your brain.This damage can cause serious problems, including blindness.
Males who have sickle cell anemia may have painful, unwanted erections. This condition is called priapism. It happens because the sickle cells block blood flow out of an erect penis. Over time, priapism can damage the penis and lead to impotence.
When red blood cells die, they release their hemoglobin. The body breaks down this protein into a compound called bilirubin. Too much bilirubin in the body can cause stones to form in the gallbladder, called gallstones.Gallstones may cause steady pain that lasts for 30 minutes or more in the upper right side of the belly, under the right shoulder, or between the shoulder blades. The pain may happen after eating fatty meals.
People who have gallstones may have nausea (feeling sick to the stomach), vomiting, fever, sweating, chills, clay-colored stools, or jaundice.
Ulcers on the Legs
Sickle cell ulcers (sores) usually begin as small, raised, crusted sores on the lower third of the leg. Leg sores may occur more often in males than in females. These sores usually develop in people who are aged 10 years or older.The cause of sickle cell ulcers isn't clear. The number of ulcers can vary from one to many. Some heal quickly, but others persist for years or come back after healing.
Multiple Organ Failure
Multiple organ failure is rare, but serious. It happens if you have a sickle cell crisis that causes two out of three major organs (lungs, liver, or kidneys) to fail. Often, multiple organ failure occurs during an unusually severe pain crisis.Symptoms of this complication are fever, rapid heartbeat, problems breathing, and changes in mental status (such as sudden tiredness or confusion).
How is Sickle Cell Anemia Diagnosed?
A simple blood test, done at any time during a person's lifespan, can detect whether he or she has sickle hemoglobin. However, early diagnosis is very important.
In the United States, all States mandate testing for sickle cell anemia as part of their newborn screening programs. The test uses blood from the same blood samples used for other routine newborn screening tests. The test can show whether a newborn infant has sickle hemoglobin.Test results are sent to the doctor who ordered the test and to the baby's primary care doctor. It's important to give the correct contact information to the hospital. This allows the baby's doctor to get the test results as quickly as possible.
Health providers from a newborn screening followup program may contact you directly to make sure you're aware of the test results.If the test shows some sickle hemoglobin, a second blood test is done to confirm the diagnosis. The second test should be done as soon as possible and within the first few months of life.
The primary care doctor may send you to a hematologist for a second blood test. A hematologist is a doctor who specializes in blood diseases and disorders. This doctor also can provide treatment for sickle cell disease if needed.
Doctors also can diagnose sickle cell disease before birth. This is done using a sample of amniotic fluid or tissue taken from the placenta. (Amniotic fluid is the fluid in the sac surrounding a growing embryo. The placenta is the organ that attaches the umbilical cord to the mother's womb.)Testing before birth can be done as early as 10 weeks into the pregnancy. This testing looks for the sickle hemoglobin gene, rather than the abnormal hemoglobin that the gene makes.
Research on blood and marrow stem cell transplants, gene therapy, and new medicines for sickle cell anemia is ongoing. The hope is that these studies will provide better treatments for the disease. Researchers also are looking for a way to predict the severity of the disease.
Blood and Marrow Stem Cell Transplant
A blood and marrow stem cell transplant can work well for treating sickle cell anemia. This treatment may even offer a cure for a small number of people.The stem cells used for a transplant must come from a closely matched donor. The donor usually is a close family member who doesn't have sickle cell anemia. This limits the number of people who may have a donor.
The transplant process is risky and can lead to serious side effects or even death. However, new transplant approaches may improve treatment for people who have sickle cell anemia and involve less risk.Blood and marrow stem cell transplants usually are used for young patients who have severe sickle cell anemia. However, the decision to give this treatment is made on a case-by-case basis.
Researchers continue to look for sources of bone marrow stem cells—for example, blood from babies' umbilical cords. They also continue to look for ways to reduce the risks of this procedure.
Gene therapy is being studied as a possible treatment for sickle cell anemia. Researchers want to know whether a normal gene can be put into the bone marrow stem cells of a person who has sickle cell anemia. This would cause the body to make normal red blood cells.
Researchers also are studying whether they can "turn off" the sickle hemoglobin gene or "turn on" a gene that makes red blood cells behave normally.
Researchers are studying several medicines for sickle cell anemia. They include:
• Decitabine: Like hydroxyurea, this medicine prompts the body to make fetal hemoglobin. Fetal hemoglobin helps prevent red blood cells from sickling and improves anemia. Decitabine might be used instead of hydroxyurea or added to hydroxyurea.
• Adenosine A2a receptor agonists: These medicines may reduce pain-related complications in people who have sickle cell anemia.
• 5-HMF: This natural compound binds to red blood cells and increases their oxygen. This helps prevent the red blood cells from sickling.
Take Steps To Prevent and Control Complications
Along with adopting healthy lifestyle habits, you can take other steps to prevent and control painful sickle cell crises. Many factors can cause sickle cell crises. Knowing how to avoid or control these factors can help you manage your pain.You may want to avoid decongestants, such as pseudoephedrine. These medicines can tighten blood vessels, making it harder for red blood cells to move smoothly through the vessels.
Avoid extremes of heat and cold. Wear warm clothes outside in cold weather and inside of air-conditioned rooms. Don't swim in cold water. Also, be cautious at high altitudes; you may need extra oxygen.If possible, avoid jobs that require a lot of heavy physical labor, expose you to extremes of heat or cold, or involve long work hours.
Don't travel in airplanes in which the cabins aren't pressurized (that is, no extra oxygen is pumped into the cabin). If you must travel in such an airplane, talk with your doctor about how to protect yourself.
Get a flu shot and other vaccines to prevent infections. You also should see your dentist regularly to prevent infections and loss of teeth. Contact your doctor right away if you have any signs of an infection, such as a fever or trouble breathing.For people who have sickle cell anemia, just like for everyone else, regular medical care and treatment for health issues are important. Your checkups may include extra tests for possible kidney, lung, and liver diseases. See a sickle cell anemia expert regularly. Also, see an eye doctor regularly to check for damage to your eyes.
Learn the signs and symptoms of a stroke. They include:
• Sudden weakness
• Paralysis (an inability to move) or numbness of the face, arms, or legs, especially on one side of the body
• Trouble speaking or understanding speech
• Trouble seeing in one or both eyes
• Problems breathing
• Dizziness, trouble walking, loss of balance or coordination, and unexplained falls
• Loss of consciousness
• Sudden and severe headache
If you think you’re having a stroke, call 9–1–1 right away. Do not drive to the hospital or let someone else drive you. Call an ambulance so that medical personnel can begin life-saving treatment on the way to the emergency room.
Get treatment and control any other medical conditions you have, such as diabetes.Talk with your doctor if you're pregnant or planning to become pregnant. Sickle cell anemia can worsen during pregnancy. You'll need special prenatal care.
Women who have sickle cell anemia also are at increased risk for an early birth or a low-birth-weight baby. However, with early prenatal care and frequent checkups, you can have a healthy pregnancy.
• Biology textbook, NCERT
• www.NHLBI (National Heart, Lung, and Blood Institute).com