Sickle Cell Disease From Screening to Cure

Sickle cell disease is an inherited disorder of haemoglobin in which red cells deform into rigid crescents, block small blood vessels and die early, causing anaemia, pain crises and progressive organ damage. Managing it well means screening early, preventing crises with supportive care and hydroxyurea, and referring the right patients in time for a cure: a bone marrow transplant today, and gene therapy as it matures.

That sequence, from screening to cure, is the protocol Dr. Sukriti Gupta, Sr. Consultant, BMT, Haematopoietic Stem Cell Transplant, Hematology, Oncology, Paediatric Haemato-Oncology & BMT, Artemis Hospitals, Gurugram, India, set out for doctors across Africa in November 2025. Her starting premise was practical. Sub-Saharan Africa and India carry a shared, heavy burden of the disease, and both manage chronically ill patients with limited resources. Clinicians in both regions therefore need common management protocols that cover early screening, prevention, timely referral based on symptoms, communication with families, and a treatment plan that accounts for the logistics patients actually face.

This guide covers the biology, symptoms and complications of sickle cell disease, and maps the three stages of care that the companion articles examine in depth:

• Sickle cell testing: electrophoresis, prenatal diagnosis and stroke screening
• Sickle cell treatment: supportive care, hydroxyurea and pregnancy
• Bone marrow transplant versus gene therapy as a cure

A shared burden across Africa and India

Dr. Gupta put the global toll at nearly 500,000 newborns with sickle cell disease each year, despite years of awareness campaigns, with about 80% of them born in sub-Saharan Africa. India carries the other large share of the burden. The overlap matters for treatment as much as for epidemiology: both regions manage large numbers of chronically affected patients with limited resources, so a protocol built for one setting translates to the other.

India has made elimination a national goal. Under the National Sickle Cell Anaemia Elimination Mission, the target is eradication by 2047. Dr. Gupta described its four pillars as regular haemoglobin electrophoresis through newborn screening, family screening programmes, encouragement of bone marrow transplant for eligible candidates, and support for the gene therapies now under development.

What causes sickle cell disease: the genetics

Sickle cell disease is caused by a single change in the HBB gene on chromosome 11, which encodes beta globin. Adult haemoglobin is a tightly organised protein made of two alpha and two beta globin chains, each a precisely folded chain of amino acids. In the sickle gene, one amino acid is swapped: glutamic acid at position 6 of the beta chain is replaced by valine. That substitution produces haemoglobin S (HbS), which folds abnormally.

How it is inherited

Sickle cell disease is autosomal recessive: a child is affected only when both copies of the gene carry an abnormal variant. Each parent of an affected child is usually a healthy-looking carrier with one sickle gene (S) and one normal gene (A). For every pregnancy of two carrier parents:

• 25% chance the child inherits two normal genes (AA) and is unaffected
• 50% chance the child inherits one of each (AS), sickle cell trait, and is a healthy carrier
• 25% chance the child inherits two sickle genes (SS) and has sickle cell disease

Dr. Gupta stressed that the affected outcome need not be SS. A parent may instead carry a different abnormal haemoglobin, such as C, D or E. A child who inherits S from one parent and C or E from the other (HbSC or HbSE disease) behaves like a sickle cell patient, usually with milder or moderate disease. This is why the laboratory work-up looks for a full spectrum of haemoglobin variants (A, A2, F, C, D, E and S) rather than for HbS alone.

Why sickled cells cause disease

Sickled red cells cause disease because they block small blood vessels and are destroyed far earlier than normal cells. A normal red cell is a flexible, rounded disc that carries oxygen through the circulation and lives for 90 to 120 days. When HbS gives up its oxygen, its molecules polymerise into long fibres that stiffen the cell and bend it into the familiar crescent or sickle shape.

Three consequences follow.

1. Vessel blockage. Sickled cells do not flow smoothly. They clog small vessels, blood flow falls, and the tissue downstream is starved of oxygen. This vaso-occlusion drives most of the acute symptoms.
2. Early destruction. A sickled red cell survives only about 20 days, Dr. Gupta noted, compared with 90 to 120 days for a normal cell. The result is chronic haemolytic anaemia, a shortage of red cells caused by their continuous destruction.
3. Futile compensation. The bone marrow responds by producing red cells at a far higher rate, but every new cell carries the same faulty haemoglobin, so the cycle continues.

Symptoms of sickle cell disease

The symptoms follow directly from anaemia and vessel blockage.

• Fatigue from chronic anaemia.
• Pain crises. Small vessels clog easily, causing severe pain in the bones and joints, and also in the chest and abdomen. These sickling, or vaso-occlusive, crises are the hallmark of the disease.
• Dactylitis. Blocked vessels in the small bones of the hands and feet cause marrow infarction and painful swelling of the fingers and toes, often the first sign of disease in infancy.
• Priapism in young men, a painful, prolonged erection caused by sickling in the penile vessels.
• Delayed growth.

Why the same genotype behaves differently

Dr. Gupta emphasised how variable the disease is. Two patients with the same HbSS genotype can have very different crises in intensity, frequency and duration. Some have short episodes of acute pain; others develop chronic pain that becomes debilitating over years. Treatment plans therefore have to be built around the individual patient's pattern, not the genotype alone.

Why dactylitis is a disease of childhood

Asked during the session whether adults present with dactylitis, Dr. Gupta explained that it is chiefly a childhood sign. In children, the small vessels of the hands are tiny and collateral circulation is poorly developed, so a single blockage starves the bone. In adults the vessels are larger and collaterals form more readily, so dactylitis becomes uncommon.

Complications of sickle cell disease, organ by organ

Repeated vessel blockage and continuous haemolysis damage almost every organ over time. Dr. Gupta noted that most of this end-organ damage becomes apparent in adulthood, which is the strongest argument for picking up the disease early in childhood.

Acute chest syndrome

Acute chest syndrome presents with chest pain, fever and breathing difficulty. Vessels in the lungs clog, often precipitated by a chest infection. Two episodes are, in Dr. Gupta's framework, among the indications to consider a bone marrow transplant.

The spleen and infection

The spleen is central to antibody-based (humoral) immunity. Repeated sickling within its vessels gradually shrinks it until it stops working, a process called autosplenectomy. Infections then become much more frequent, particularly with encapsulated bacteria such as Streptococcus pneumoniae, and meningitis is more common in children with sickle cell disease. This is the reason for penicillin prophylaxis and pneumococcal vaccination, covered in the treatment article.

Haemolytic emergencies

Two acute crises cause a sudden, dangerous fall in haemoglobin.

• Hyperhaemolytic crisis. Acute stress, such as high altitude or a febrile illness, accelerates red cell destruction. The products of the destroyed cells can compromise blood flow to the kidneys and cause acute kidney injury.
• Aplastic crisis. Parvovirus B19 infects the precursors of red cells and temporarily halts their production. In a healthy person this passes unnoticed; in sickle cell disease, where red cells survive only weeks, the bone marrow shutdown causes a rapid, severe drop in haemoglobin.

The three stages of sickle cell disease management

Sickle cell disease management moves through three stages in Dr. Gupta's protocol: early diagnosis and family screening, prevention of crises, and timely referral for a cure. Each is the subject of a companion article.

1. Diagnose early and screen the family

Haemoglobin electrophoresis is the definitive test: now easily available even in resource-limited settings, with results within a day. Once one child is diagnosed, siblings and parents should be screened and the family offered genetic counselling. For carrier couples, amniocentesis and chorionic villus sampling allow diagnosis during pregnancy. From two years of age, transcranial Doppler ultrasound identifies children at high risk of stroke before a stroke occurs. These tests, and how to read them, are covered in the testing article.

2. Prevent crises and protect the organs

Supportive care is the daily work of sickle cell medicine: regular clinic visits even when well, penicillin prophylaxis, vaccination, generous hydration, blood transfusion or red cell exchange, and hydroxyurea, a drug that raises fetal haemoglobin and so reduces sickling. Pregnancy needs its own plan. The detail, including Dr. Gupta's view of the newer drugs that won and then lost regulatory favour, is in the treatment article.

3. Refer for a cure in time

A bone marrow transplant replaces the patient's blood-forming stem cells with healthy donor cells and is, for now, the established cure. Gene therapy, which uses the patient's own genetically modified cells, was approved in the United States in 2023 and is not yet available in India. Choosing between them turns on symptoms, donor availability, age, organ function, urgency and money. Dr. Gupta's decision framework, her centre's outcomes and costs, and her candid view of the trade-offs are set out in the transplant versus gene therapy article.

Why collaboration between treating doctors matters

The success of a transplant, Dr. Gupta argued, depends heavily on what happens after the patient flies home. In her experience, chronic graft-versus-host disease (in which the donor's immune cells attack the patient's tissues) and relapse could very well be prevented with proper medicines and timely follow-up in the home country. Her centre stays in contact with families by WhatsApp, and she sees the treating physician, paediatrician or general practitioner at home as an essential partner in long-term care.

The questions doctors raised during the session, on haemoglobin S thresholds, stroke prevention, hydroxyurea in pregnancy, transplant costs and age limits, and gene therapy, are collected in the Live Discussion. For other specialists' perspectives on the transplant pathway within haematology, see Dr. Dharma Choudhary's evidence on sickle cell transplant outcomes and Dr. Vikas Dua's guide to bone marrow transplant for sickle cell anaemia.