Sickle cell disease is a group of inherited blood disorders that causes red blood cells to take on an unusual crescent or sickle shape, leading to blocked blood vessels, episodes of severe pain, and serious health complications that affect many parts of the body.

Understanding Sickle Cell Disease Worldwide

Sickle cell disease affects millions of people around the globe, with the burden falling heaviest on certain populations. In 2021, an estimated 7.74 million people were living with this condition worldwide, with approximately 515,000 new births occurring in families carrying the disease.^[8] The geographic distribution of sickle cell disease is striking, with sub-Saharan Africa accounting for nearly 80 percent of all global cases.^[8]

In the United States, between 70,000 and 100,000 Americans live with sickle cell disease, making it the most common form of an inherited blood disorder in the country.^[4] The condition predominantly affects people of African descent, with approximately 1 in 365 Black Americans born with the disease and about 1 in 12 carrying the sickle cell gene.^[2][4] However, the disease is not limited to one ethnic group. It also affects people with southern European, Middle Eastern, Asian Indian, Hispanic, Mediterranean, and Caribbean ancestry.^[4][6]

The impact of sickle cell disease extends beyond individual suffering. In 2021, the condition caused 81,100 deaths in children under five years old globally, making it the 12th leading cause of death in this age group when considering the total mortality burden.^[8] Traditional mortality recording significantly underestimates the true impact of sickle cell disease, with actual deaths being 11 times higher than cause-specific statistics suggest.^[8]

What Causes Sickle Cell Disease

Sickle cell disease arises from a genetic change, specifically a mutation in the HBB gene, which provides instructions for making beta-globin, an important component of hemoglobin, the protein inside red blood cells that carries oxygen throughout the body.^[6][8] This mutation is remarkably specific: it involves a single base change that causes the replacement of one amino acid (glutamic acid) with another (valine) in the sixth position of the beta-globin chain.^[14]

When this genetic change occurs, the body produces an abnormal form of hemoglobin called hemoglobin S instead of normal hemoglobin A.^[2] The presence of hemoglobin S causes red blood cells to change shape under certain conditions, particularly when oxygen levels are low. Instead of maintaining their normal round, flexible disc shape, these cells become rigid and take on a characteristic crescent or sickle shape.^[1]

For someone to develop sickle cell disease, they must inherit two copies of the sickle cell gene, one from each biological parent.^[2] When both parents carry at least one copy of the gene, there is a 1 in 4 chance with each pregnancy that their child will be born with sickle cell disease.^[5] People who inherit only one copy of the sickle cell gene from one parent and a normal gene from the other parent have what is called sickle cell trait. These individuals usually do not experience symptoms of sickle cell disease but can pass the gene to their children.^[2]

Who Is at Higher Risk

Certain groups face significantly higher risks of inheriting sickle cell disease based on their ancestry. People with African or Black American heritage are at greatest risk, but the condition is also more common among individuals whose families come from Central and South America, the Middle East, India, Mediterranean countries including Sicily, and the Arab Gulf states.^[2][4][6]

The risk of having a child with sickle cell disease increases dramatically when both parents carry the sickle cell gene. If two people with sickle cell trait have children together, each pregnancy carries a 25 percent chance of producing a child with the disease, a 50 percent chance of producing a child with the trait, and a 25 percent chance of producing a child with neither.^[7] Understanding family history becomes crucial for couples planning to have children, and genetic counseling can help prospective parents understand their risks.^[5]

Beyond genetic inheritance, certain environmental and lifestyle factors can trigger complications in people already living with sickle cell disease. Dehydration increases the risk of a sickle cell crisis, so people living in hot climates or those who don’t drink enough fluids face greater challenges.^[5] High-altitude environments, where oxygen is less available, can also trigger problems because low oxygen levels promote the sickling of red blood cells.^[5] Extreme temperatures, whether hot or cold, and sudden temperature changes can also set off painful episodes.^[5]

Recognizing the Symptoms

Symptoms of sickle cell disease typically begin to appear when babies are between five and six months old, although some children may have few symptoms initially and lead relatively normal lives for periods of time.^[5][9] The severity and frequency of symptoms vary widely from person to person. Some individuals experience mild effects with few complications, while others face severe, life-threatening problems that significantly impact their daily lives.^[5]

Anemia, or low red blood cell count, is a constant feature of sickle cell disease. This occurs because sickled red blood cells break apart easily and die much faster than normal red blood cells. While healthy red blood cells typically live for about 120 days, sickled cells usually die in just 10 to 20 days, creating a persistent shortage.^[3][7] This chronic shortage means the body cannot get enough oxygen to all its tissues and organs, leading to persistent fatigue, weakness, and paleness.^[3]

Episodes of severe pain, called pain crises or sickle cell crises, represent one of the most challenging aspects of living with this condition. These episodes occur when sickled red blood cells get stuck in small blood vessels and block normal blood flow.^[1] The pain develops suddenly and can be excruciating, most commonly affecting the chest, abdomen, back, arms, and legs.^[3] The intensity and duration of these episodes vary considerably. Some people experience only a few pain crises per year, while others endure a dozen or more. Each episode can last anywhere from a few hours to several days, and severe crises often require hospitalization for management.^[3]

Young children often show their first symptoms through painful swelling of the hands and feet, a condition known as dactylitis. This occurs when sickled cells block blood flow to these extremities.^[3][6] Many people with sickle cell disease also develop jaundice, a yellowing of the skin and whites of the eyes, caused by the breakdown of red blood cells releasing a substance called bilirubin that builds up in the system.^[16]

Other symptoms include increased vulnerability to infections because sickle cell disease affects the spleen, an organ crucial for fighting infections.^[3] This makes even common illnesses like the flu potentially dangerous for people with sickle cell disease. Some individuals experience delayed growth and development, problems with vision, strokes, lung complications called acute chest syndrome, kidney problems, and in males, painful prolonged erections called priapism.^[1][3]

Prevention Strategies

While sickle cell disease itself cannot be prevented once inherited, there are important strategies to prevent the condition from occurring in future generations and to prevent complications in those living with the disease. For couples planning to have children, genetic counseling and testing can identify whether they carry the sickle cell gene and what risks they face of having a child with the disease.^[5] Prenatal testing can diagnose sickle cell disease in an unborn baby by sampling amniotic fluid or tissue from the placenta.^[4]

All newborns in the United States are now tested for sickle cell disease as part of routine newborn screening, typically through a blood test taken from the heel.^[4][5] Early diagnosis allows for immediate implementation of preventive measures that can dramatically improve outcomes and quality of life.

For individuals living with sickle cell disease, preventing complications requires ongoing vigilance and healthy habits. Staying well-hydrated by drinking eight to ten glasses of water daily helps reduce the risk of pain crises, as dehydration is a known trigger.^[17][19] Avoiding extreme temperatures and dressing appropriately for the weather helps prevent temperature-related triggers.^[18]

Infection prevention is critical. People with sickle cell disease should take daily antibiotics, usually penicillin, particularly during childhood, to reduce infection risk.^[13] Staying current with all recommended vaccinations is essential, including annual flu shots and vaccines for pneumonia and meningococcal disease, because common illnesses can quickly become dangerous.^[17][19] Even with preventive antibiotics and vaccines, anyone with sickle cell disease who develops a fever should seek medical attention immediately, as this may signal a serious infection.^[15]

Maintaining a healthy lifestyle supports overall well-being. This includes eating nutritious foods rich in fruits, vegetables, whole grains, and protein; getting adequate sleep; and engaging in moderate physical activity.^[19][20] However, it’s important to avoid overexertion and rest when tired, as intense exercise that causes severe breathlessness can trigger complications.^[18] People with sickle cell disease should also avoid alcohol, which can cause dehydration, and never smoke, as smoking can trigger serious lung complications.^[18]

How the Body Changes in Sickle Cell Disease

Understanding what happens inside the body when someone has sickle cell disease helps explain why the symptoms occur. The fundamental problem lies in the structure and behavior of hemoglobin, the oxygen-carrying protein inside red blood cells. Normal hemoglobin allows red blood cells to remain soft, round, and flexible, enabling them to squeeze through even the tiniest blood vessels to deliver oxygen to every part of the body.^[1]

When hemoglobin S is present in red blood cells, the situation changes dramatically. Under conditions of low oxygen, hemoglobin S molecules undergo a process called polymerization, where they stick together and form long, rigid structures that stretch and distort the cell membrane.^[9][14] This physical transformation causes the characteristic sickle or crescent shape. These sickled cells are stiff and sticky, unable to bend and squeeze through narrow blood vessels the way normal cells do.^[1]

As sickled cells travel through the bloodstream, they tend to get stuck at branching points and in small blood vessels, creating blockages that prevent normal blood flow. When blood flow is blocked, the tissues and organs downstream don’t receive adequate oxygen, triggering the severe pain that characterizes sickle cell crises.^[1] Different parts of the body can be affected depending on where the blockages occur, explaining why pain can appear in the bones, joints, chest, abdomen, or other locations.

The rapid breakdown of sickled red blood cells creates multiple cascading problems. The shortened lifespan of these cells means the bone marrow, where blood cells are produced, cannot keep up with the constant need for replacement, resulting in chronic anemia.^[3] When red blood cells break down, they release hemoglobin and other substances that can damage organs over time. The liver works to process this breakdown, but the excess bilirubin produced causes the yellowing of skin and eyes seen in jaundice.^[16]

The spleen, an organ that normally filters the blood and helps fight infections, becomes damaged early in the disease process. Repeated episodes of sickling in the spleen can cause it to become scarred and shrunken, losing its ability to function properly.^[7] This is why people with sickle cell disease face increased risks of certain bacterial infections and need preventive antibiotics and additional vaccinations.

Over time, the repeated episodes of blocked blood flow and oxygen deprivation can cause cumulative damage to multiple organs. The kidneys may become scarred and lose function, the lungs can develop complications including pulmonary hypertension, the bones may suffer damage to the hip joint and other areas, and the eyes can experience vision problems.^[1][8] The heart may become enlarged from working harder to pump blood and compensate for chronic anemia.^[7] In children, blockages in blood vessels supplying the brain can lead to strokes, which is why regular monitoring and preventive measures are so important.^[3]