Sickle cell disease

What is it?

According to the NHLBI: a group of inherited disorders that affect haemoglobin, the main protein that carries oxygen in red blood cells. The cells turn into crescent (sickle) shapes because of a genetic mutation, and do not bend easily so they obstruct blood flow. MedlinePlus states that sickled cells break down faster (10 to 20 days versus 90 to 120 days for normal cells) and may block blood vessels. The NHS defines it as an inherited condition affecting red blood cells that may cause pain, swelling and tiredness and is usually lifelong.

Types according to the CDC: HbSS (sickle cell anaemia), usually the most severe; HbSC, usually milder; HbS beta thalassaemia, ranging from severe (beta zero) to mild (beta plus); and rare types (HbSD, HbSE, HbSO) of varying severity. The CDC and NHLBI distinguish the disease from sickle cell trait (HbAS), in which a person inherits one abnormal gene and usually shows no signs of the disease. This page does not cover the types of the disease in detail.

Prevalence according to the NHLBI: it affects more than 100,000 people in the United States and 8 million people worldwide; in the United States more than 90% of people with it are Black or African American (non-Hispanic) and an estimated 3% to 9% are Hispanic. About 1 in 13 Black babies is born with the trait, and about 1 in 365 Black babies is born with the disease.

Causes

According to the NHLBI: an inherited disorder caused by mutations in haemoglobin genes that produce a defective protein called haemoglobin S. A person has the disease when they inherit two altered genes (one from each parent) that produce haemoglobin S, or a haemoglobin S gene with a gene for another defective type such as beta thalassaemia or haemoglobin C.

A carrier of the trait inherits a sickle gene from one parent and a normal gene from the other, and produces about 60% normal haemoglobin (A) and 40% haemoglobin S (NHLBI). If both parents carry the trait, each child has: a 25% (1 in 4) chance of inheriting two normal genes, 50% (1 in 2) of inheriting one gene of each kind (a carrier), and 25% (1 in 4) of inheriting two haemoglobin S genes, i.e. the disease.

The NHLBI states that having a haemoglobin S gene protects against severe malaria, which explains its high prevalence in malaria-endemic regions.

Risk factors

According to the NHLBI: the disease is more common in people of African, Middle Eastern, Mediterranean, Central and South American and South Asian descent. The NHS lists African, Caribbean, Mediterranean, Asian (South and Southeast) and Middle Eastern backgrounds. The main driver is inheriting the gene from both parents; carriers of the trait do not develop the disease but may pass the gene to their children (NHS).

Symptoms

Signs usually begin in the first year, around 5 months of age (CDC), and the NHLBI lists early symptoms: jaundice (yellowing of the skin or whites of the eyes), tiredness or irritability from anaemia, and dactylitis (painful swelling of the hands and feet).

According to the NHLBI: a "pain crisis", "sickle cell crisis" or "vaso-occlusive crisis" is an event of sudden severe pain. The NHS lists other symptoms: pain in the bones, joints, muscles and chest, weakness and tiredness, difficulty breathing, repeated infections, abdominal pain, and there may be blurred vision, fever or a persistent painful erection. Triggers mentioned by the NHS include dehydration, temperature changes and stress.

How is it diagnosed?

According to the NHLBI: blood tests reveal the presence of haemoglobin S, and genetic tests determine whether a person carries one or two copies of the sickle gene, and help confirm the diagnosis when blood results are unclear. Diagnosis can be made before birth with a sample of amniotic fluid or placenta, from week 8 to 10 of pregnancy, and it detects the gene but does not predict the severity of symptoms.

Newborn screening: all fifty US states run a newborn heel-prick screening programme, and it detects the disease and carriers of the trait, and genetic counselling is offered when a carrier is found (NHLBI). In most births in the United States the disease is detected at birth by routine screening (CDC). This page does not cover screening programmes in other countries.

Treatment

The treatment categories usually used are listed here; this is not a prescription. The doctor chooses the plan according to each person's condition; do not change any medicine or dose without a specialist.

According to the NHLBI: hydroxyurea is an oral medicine that reduces sickling of cells and is prescribed from the age of 9 months, and its benefits include fewer pain attacks, acute chest syndrome, anaemia and hospital admissions. The page lists other medicines for pain and complications, including L-glutamine and crizanlizumab-tmca, and pain medicines from ordinary painkillers (acetaminophen or ibuprofen) for mild to moderate pain to prescription opioids for severe or chronic pain. The NHS mentions hydroxycarbamide.

Preventing infection: daily penicillin for children to lower the risk of blood infection (NHLBI), and regular vaccinations including annual flu and COVID-19 as recommended, and pneumonia and meningococcal vaccines (NHLBI, living-with-the-disease page).

Red blood cell transfusion raises the number of healthy cells, and is used for acute complications, stroke, acute chest syndrome, before surgery and to prevent stroke in those at high risk (NHLBI). The NHS also mentions exchange transfusion. Blood and bone marrow transplant is a potential curative treatment that needs a matched donor, often a relative, and the NHLBI states a 90% success rate in children with risks including graft-versus-host disease, infection, infertility and graft failure. Two gene therapies were approved in December 2023 (exagamglogene autotemcel and lovotibeglogene autotemcel). MedlinePlus states that gene therapy is for people aged 12 and over who have frequent attacks. Supportive approaches are also mentioned, such as cognitive behavioural therapy, massage, meditation and virtual reality for pain.

Follow-up

The NHLBI advises people with the disease to see their healthcare provider regularly, as most see them every 3 to 12 months, and to take hydroxyurea and other medicines as prescribed. The doctor determines the right schedule for each case.

Complications

According to the CDC: complications include pain attacks, infections, acute chest syndrome and stroke. The NHLBI mentions problems of the lungs, eyes and kidneys and chronic pain, and the NHS mentions a higher risk of stroke, vision problems and damage to organs such as the lungs, heart and kidneys. The NHLBI mentions emergencies including severe anaemia (splenic sequestration or aplastic crisis).

Prevention

Inheritance cannot be prevented, but carrying the trait can be learned through testing: prenatal screening, newborn screening and genetic counselling for carriers (NHLBI). The NHS mentions screening pregnant women before week 10 and screening a carrier of the trait with a blood test, and these are services specific to UK programmes and this page does not cover your country's programmes. To reduce complications: avoid extreme heat or cold, sudden temperature changes, dehydration and vitamin deficiency, and manage stress (NHLBI).

Living with it

According to the CDC and NHLBI: with appropriate care many people with the disease live full lives and take part safely in most activities. The NHLBI recommends managing stress (a common trigger for complications), enough sleep (7 to 9 hours), regular physical activity, a heart-healthy diet and quitting smoking.

Common questions