Sickle cell disease is an inherited blood disorder that changes the shape of red blood cells and, with them, the way oxygen moves through the body. Instead of staying soft and round, the affected cells can turn stiff and curved like a crescent or a sickle, breaking down early and clogging small blood vessels. The result is a lifelong condition marked by anemia, episodes of pain, and a higher risk of infection and organ damage. This guide explains what sickle cell disease is, how to recognize its symptoms, why it happens, how doctors confirm it with blood tests, and what today’s treatments, including two newly approved gene therapies, can offer.
What is sickle cell disease?
Sickle cell disease is a group of inherited red blood cell disorders caused by a change in the HBB gene, which carries the instructions for making part of hemoglobin. Healthy red cells are packed with hemoglobin, the iron-rich protein that carries oxygen; to see how this protein is measured, you can review what a hemoglobin blood test measures and why it matters. In sickle cell disease, the gene change produces an abnormal form called hemoglobin S. When oxygen levels drop, hemoglobin S clumps together and stretches the normally round, flexible red cell into a rigid sickle shape.
These misshapen cells cause trouble in two ways. They break apart far sooner than normal cells, surviving only about 10 to 20 days instead of the usual 120, which leaves the body short of red cells. They also snag and pile up inside small blood vessels, blocking the flow of oxygen-rich blood to organs. Sickle cell disease is the most common inherited blood disorder in the United States, affecting roughly 100,000 people, and it occurs most often in those with African ancestry, though it also affects people of Hispanic, Mediterranean, Middle Eastern, and South Asian descent. The most common and usually most severe form is HbSS, often called sickle cell anemia, while HbSC and HbS beta-thalassemia tend to be milder.
Symptoms of sickle cell disease
Symptoms usually begin in the first year of life, often around five or six months of age, and they vary widely from one person to another. The constant early destruction of red cells leaves many people with chronic anemia and fatigue; because the body cannot replace the lost cells fast enough, oxygen delivery falls, and to understand this shortfall you can read this guide to anemia symptoms, causes, and treatments. The hallmark of the disease is the pain crisis, or vaso-occlusive crisis, in which blocked vessels cause sudden pain that can strike the bones, chest, back, or abdomen and last from hours to days.
Many people also develop jaundice, a yellowing of the skin and eyes, as worn-out cells release a pigment called bilirubin. Infants may have painful swelling of the hands and feet, known as dactylitis, sometimes as the first noticeable symptom. Because the spleen is often damaged early, children with sickle cell disease are more vulnerable to serious infections.
| Common symptom | What it usually involves |
|---|---|
| Chronic anemia and fatigue | Ongoing tiredness, paleness, and shortness of breath from a persistent shortage of red cells |
| Pain crises | Episodes of sudden pain in the bones, chest, back, or abdomen when blood vessels become blocked |
| Jaundice | Yellowing of the skin and the whites of the eyes as red cells break down |
| Swelling of hands and feet | Painful puffiness called dactylitis, often one of the earliest signs in infants |
| Frequent infections | A raised risk of serious infection because the spleen is damaged early in life |
Causes and risk factors
Sickle cell disease is caused entirely by genetics; it is not contagious and cannot be caught or passed on through contact. The condition follows an autosomal recessive pattern, which means a person must inherit two copies of the changed HBB gene, one from each parent, to develop the disease. A single copy produces sickle cell trait, a carrier state that usually causes no symptoms but can be passed to children.
When both parents carry the trait, each pregnancy carries a one-in-four chance the child will have sickle cell disease and a one-in-two chance of inheriting the trait. The main risk factor is therefore family ancestry: the gene is far more common in families from regions where malaria has historically been widespread, because carrying a single copy offers some protection against that infection.
Types of sickle cell disease and sickle cell trait
Sickle cell disease is an umbrella term covering several genotypes that differ in severity. HbSS, in which a person inherits two hemoglobin S genes, is the most common and generally the most serious form and is the one usually meant by sickle cell anemia. HbSC pairs one hemoglobin S gene with a different variant called hemoglobin C and often causes milder illness, while HbS beta-thalassemia combines a hemoglobin S gene with a beta-thalassemia gene and ranges from mild to severe.
Sickle cell trait is different from the disease. People with the trait carry one hemoglobin S gene and one normal gene, make mostly normal hemoglobin, and typically live without symptoms. In rare situations, such as extreme exertion, severe dehydration, or very low oxygen at high altitude, the trait can occasionally cause problems, but for most carriers the main significance is the chance of passing the gene to a child. This is why genetic counseling is offered to couples who both carry the trait.
How sickle cell disease is diagnosed
Because sickle cell disease is present from birth, most people in the United States are identified through universal newborn screening, which tests a few drops of blood from every baby’s heel. A positive screen is always confirmed with more specific blood testing before a diagnosis is made, and that laboratory work sits at the center of the process.
The confirming test is hemoglobin electrophoresis, sometimes done as high-performance liquid chromatography or isoelectric focusing, which separates the different types of hemoglobin and shows whether hemoglobin S is present and in what amount. Supporting blood work fills in the picture: doctors review the results of a complete blood count to measure the degree of anemia, and they also check the reticulocyte count that shows how quickly the marrow is making new red cells. Because sickled cells break apart early, laboratories often measure the bilirubin level that climbs when red cells are destroyed and look at lactate dehydrogenase as another sign of cell breakdown; you can understand what an LDH blood test reveals about red cell turnover. A blood smear examined under the microscope may show the sickle-shaped cells directly, and prenatal or carrier testing can confirm the genetics before or during a pregnancy.
| Test | What it shows | Role in diagnosis |
|---|---|---|
| Newborn screening | An early signal of abnormal hemoglobin from a heel-prick sample | First step, done for every baby in the United States |
| Hemoglobin electrophoresis or HPLC | The exact types and amounts of hemoglobin, including hemoglobin S | Confirms the diagnosis and the specific genotype |
| Complete blood count | The number of red cells and the hemoglobin level | Measures how severe the anemia is |
| Reticulocyte count | How fast the bone marrow is releasing new red cells | Shows the marrow responding to ongoing cell loss |
| Bilirubin and LDH | Byproducts released when red cells are destroyed | Reflect the degree of red cell breakdown |
Treatment and management
Care is tailored to each person and aims to reduce crises, ease pain, and prevent complications. Hydroxyurea is the long-standing cornerstone of daily treatment; it prompts the body to make more fetal hemoglobin, a form that resists sickling, and it lowers the frequency of pain crises and acute chest episodes. Other approved medicines include L-glutamine, which can reduce crises, and crizanlizumab, an infused antibody that blocks a protein called P-selectin to help keep cells from sticking inside vessels. Everyday care also includes folic acid to support red cell production and prompt pain relief during crises.
Blood transfusions play an important role, both in emergencies and to prevent complications such as stroke, but repeated transfusions can overload the body with iron, so care teams monitor the ferritin level that reflects the body’s iron stores and may add medicine to remove the excess. For children, penicillin taken daily in the early years and a full schedule of vaccinations sharply reduce the danger of life-threatening infection.
The most far-reaching change in decades has been the arrival of gene therapy. In December 2023 the U.S. Food and Drug Administration approved the first two gene therapies for sickle cell disease, Casgevy and Lyfgenia, for people aged 12 and older who have recurrent pain crises. Casgevy is notable as the first CRISPR-based therapy ever approved, editing a person’s own blood-forming cells to switch fetal hemoglobin back on, while Lyfgenia adds a working gene to those cells. An allogeneic stem cell, or bone marrow, transplant from a matched donor remains the only long-established treatment that can potentially cure the disease. It is worth noting that voxelotor, sold as Oxbryta, was withdrawn worldwide by its manufacturer in September 2024 over safety concerns and is no longer available, so it is no longer part of current treatment.
Preventing complications and daily management
The underlying gene change cannot be prevented, but many crises and complications can be reduced with steady, proactive care that focuses on avoiding known triggers and staying ahead of problems with regular medical visits.
- Drink plenty of fluids and avoid dehydration, which makes blood thicker and easier to block.
- Stay warm and avoid sudden temperature changes, cold water, and very high altitudes that can set off a crisis.
- Keep up with recommended vaccinations and, for young children, take prescribed penicillin to prevent infection.
- Avoid smoking and extreme physical exertion, and treat any fever as a medical emergency that needs prompt attention.
- Attend regular checkups so complications can be caught early, including screening that can identify children at risk of stroke.
These steps do not replace medical treatment, but they can meaningfully lower how often crises occur and help protect organs over time. Anyone living with the condition should build a plan with their care team rather than managing symptoms alone.
Complications and long-term outlook
Over time, blocked vessels and the loss of red cells can affect nearly every organ. Blocked vessels in the brain can cause a stroke, even in young children, and you can review the warning signs described in this guide to stroke. Acute chest syndrome, a dangerous mix of blocked vessels and infection in the lungs, is a leading cause of hospitalization. Other complications include splenic sequestration, priapism, gallstones, leg ulcers, pulmonary hypertension, kidney disease, and retinal damage that can threaten vision.
The outlook has improved dramatically. With newborn screening, vaccination, penicillin in childhood, hydroxyurea, and coordinated specialty care, most children in the United States now survive into adulthood and many live active lives. Life expectancy still tends to be shorter than average, and the burden of pain and complications remains real, but earlier diagnosis and newer therapies are steadily changing what the disease means for those who live with it.
Latest scientific advances in sickle cell disease research
The biggest recent shift has been the move of gene therapy from the laboratory into approved care. According to PubMed, an editorial reviewing the landmark 2023 decisions described how regulators approved Casgevy, the first CRISPR-Cas9 gene-editing therapy ever authorized, along with Lyfgenia, for people with sickle cell disease and recurrent crises (Parums, 2024). Both work by changing a patient’s own blood-forming stem cells so they make hemoglobin that does not sickle. What this means for you: a one-time, potentially curative treatment now exists for eligible patients aged 12 and older, though it involves an intensive process at specialized centers, so it is worth discussing eligibility and trade-offs with a hematologist.
Researchers have also begun to measure how well these therapies perform. A 2026 systematic review pooling results across nine clinical programs and 148 treated patients reported that severe pain crises resolved in essentially all patients in the main lovotibeglogene cohort, that nearly all patients in the exagamglogene cohort stayed free of severe crises over the follow-up window, and that treated patients became free of transfusions (Shaik and Divers, 2026). What this means for you: the early results are encouraging, but the review stressed that the studies were small and single-armed and that long-term safety and durability are still being tracked, so these are promising rather than settled answers.
Attention is now turning to making gene therapy safer, cheaper, and more widely available. A 2026 review tracing the path of gene therapy for sickle cell disease highlighted next-generation approaches such as base editing, gentler conditioning that avoids harsh chemotherapy, and delivery methods that could one day treat cells inside the body, while flagging cost and access as major hurdles (Tardif et al., 2026). What this means for you: today’s gene therapies are only the beginning, and the research aims to extend these options to younger children and to the many patients worldwide who cannot yet reach them.
Glossary of key terms
| Term | Definition |
|---|---|
| Hemoglobin S | The abnormal form of hemoglobin that clumps together and distorts red cells in sickle cell disease. |
| Vaso-occlusive crisis | An episode of pain caused by sickled cells blocking blood flow through small vessels. |
| Hemolytic anemia | A shortage of red cells caused by their breaking down faster than the body can replace them. |
| HBB gene | The gene that carries instructions for part of hemoglobin; a change in it causes sickle cell disease. |
| Fetal hemoglobin | A form of hemoglobin made before birth that resists sickling; several treatments aim to raise it. |
| Sickle cell trait | The carrier state, with one changed gene, that usually causes no symptoms but can be inherited. |
| Acute chest syndrome | A serious lung complication combining blocked vessels and infection, needing urgent care. |
| Hydroxyurea | A daily medicine that raises fetal hemoglobin and reduces the frequency of pain crises. |
| Dactylitis | Painful swelling of the hands and feet, often the first sign of sickle cell disease in infants. |
| Gene therapy | A treatment that changes a person’s own cells to correct or work around the disease. |
Frequently asked questions
What is the difference between sickle cell disease and sickle cell trait?
Sickle cell disease means a person inherited two copies of the changed gene, one from each parent, and has the illness. Sickle cell trait means a person inherited only one copy and is a carrier. People with the trait make mostly normal hemoglobin and usually have no symptoms, but they can pass the gene to their children. When both parents carry the trait, each pregnancy has a one-in-four chance of producing a child with the disease.
What triggers a sickle cell pain crisis?
A pain crisis happens when sickled cells block blood flow in small vessels. Common triggers include dehydration, infection, cold temperatures, sudden temperature changes, low oxygen at high altitude, and physical or emotional stress. Not every crisis has an obvious cause, but staying hydrated, keeping warm, treating infections early, and avoiding extreme exertion can lower how often they occur. Severe or unusual pain should be evaluated promptly.
Is there a cure for sickle cell disease?
A cure is now possible for some people. A stem cell, or bone marrow, transplant from a matched donor has long been able to cure the disease, and in December 2023 two gene therapies, Casgevy and Lyfgenia, were approved in the United States for patients aged 12 and older with recurrent crises. These treatments are intensive, are offered only at specialized centers, and are not yet options for everyone, so eligibility is best discussed with a hematologist.
How is sickle cell disease diagnosed?
In the United States, sickle cell disease is usually first detected through routine newborn screening. A positive screen is confirmed with hemoglobin electrophoresis or a similar test that identifies hemoglobin S. Additional blood tests, including a complete blood count, a reticulocyte count, and markers of red cell breakdown, help doctors judge how severe the disease is. Carrier and prenatal testing are also available for family planning.
What medicines are used to treat sickle cell disease?
Hydroxyurea is the main daily medicine and works by raising fetal hemoglobin to reduce crises. Other approved options include L-glutamine and crizanlizumab, an infused medicine that helps keep cells from sticking in vessels. Folic acid supports red cell production, and pain medicines are used during crises. Blood transfusions treat severe anemia and help prevent stroke. Voxelotor, once used, was withdrawn from the market in 2024 and is no longer available.
Can someone with sickle cell disease live a long life?
Many people with sickle cell disease now live well into adulthood, thanks to newborn screening, vaccines, penicillin in childhood, hydroxyurea, and coordinated specialty care. Life expectancy is still generally shorter than average, and complications can build over time, but earlier diagnosis and newer therapies continue to improve the outlook. Regular care with a team experienced in the disease makes a meaningful difference in both length and quality of life.
Sources
- Centers for Disease Control and Prevention — About Sickle Cell Disease — CDC Sickle Cell Disease, 2024 — cdc.gov
- National Heart, Lung, and Blood Institute — Sickle Cell Disease — NHLBI, NIH, 2024 — nhlbi.nih.gov
- Cleveland Clinic — Sickle Cell Disease: Symptoms, Causes and Types — Cleveland Clinic Health Library, 2023 — my.clevelandclinic.org
- Mayo Clinic — Sickle Cell Anemia: Symptoms and Causes — Mayo Clinic, 2024 — mayoclinic.org
- U.S. Food and Drug Administration — FDA Alerts About the Voluntary Withdrawal of Oxbryta — FDA Drug Safety, 2024 — fda.gov
- Parums DV — Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent Beta-Thalassemia — Medical Science Monitor, 2024 — doi.org/10.12659/MSM.944204
- Shaik MY, Divers S — Efficacy, Safety, and Treatment-Delivery Feasibility of Autologous Gene Therapy for Sickle Cell Disease: A Systematic Review — European Journal of Haematology, 2026 — doi.org/10.1111/ejh.70260
- Tardif M, Saby M, Forte S, Pincez T — The Journey of Gene Therapy in Sickle Cell Disease: How Molecular Advances Meet Clinical Care — Cells, 2026 — doi.org/10.3390/cells15100939
Further reading
- Learn why the breakdown of red cells can lead to gallstones by reading this guide to gallstones causes, symptoms, and treatment.
- Understand how sickled cells can harm the kidneys over time by reviewing this guide to chronic kidney disease.
- See why folic acid supports the constant production of new red cells by reading this explanation of folic acid blood levels.
- Explore another core red cell measurement by reading this guide to hematocrit blood test results.
- Build a fuller picture of your own bloodwork with this guide to reading reference ranges, flags, and trends in a lab report.
Understand your lab results with BloodSense
A sickle cell diagnosis rests on laboratory testing, from the hemoglobin electrophoresis that identifies hemoglobin S to the complete blood count, reticulocyte count, and markers of red cell breakdown that show how the disease is affecting your body. Those same blood tests can be hard to interpret on your own, especially when a report mentions hemoglobin types, reference ranges, or signs of hemolysis. BloodSense translates a full lab report into plain language, showing where each marker sits relative to its reference range and helping you understand what your results actually mean for your health.
