Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person’s parents. The most common type is known as sickle cell anaemia (SCA). It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells.
This leads to a rigid, sickle-like shape under certain circumstances. Problems in sickle cell disease typically begin around 5 to 6 months of age. A number of health problems may develop, such as attacks of pain (“sickle cell crisis”), anemia, swelling in the hands and feet, bacterial infections and stroke.Long-term pain may develop as people get older. The average life expectancy in the developed world is 40 to 60 years.
Sickle cell disease occurs when a person inherits two abnormal copies of the haemoglobin gene, one from each parent. This gene occurs in chromosome 11. Several subtypes exist, depending on the exact mutation in each haemoglobin gene. An attack can be set off by temperature changes, stress, dehydration and high altitude.
A person with a single abnormal copy does not usually have symptoms and is said to have sickle cell trait. Such people are also referred to as carriers.
In HbS, the complete blood count reveals haemoglobin levels in the range of 6–8 g/dl with a high reticulocyte count (as the bone marrow compensates for the destruction of sickled cells by producing more red blood cells). In other forms of sickle cell disease, Hb levels tend to be higher. A blood film may show features of hyposplenism (target cells and Howell-Jolly bodies).
Sickling of the red blood cells, on a blood film, can be induced by the addition of sodium metabisulfite. The presence of sickle haemoglobin can also be demonstrated with the “sickle solubility test”. A mixture of haemoglobin S (HbS) in a reducing solution (such as sodium dithionite) gives a turbid appearance, whereas normal Hb gives a clear solution.
Abnormal haemoglobin forms can be detected on haemoglobin electrophoresis, a form of gel electrophoresis on which the various types of haemoglobin move at varying speeds. Sickle cell haemoglobin (HgbS) and haemoglobin C with sickling (HgbSC)—the two most common forms—can be identified from there. The diagnosis can be confirmed with high-performance liquid chromatography. Genetic testing is rarely performed, as other investigations are highly specific for HbS and HbC.
Diagnosis is by a blood test, and some countries test all babies at birth for the disease. Diagnosis is also possible during pregnancy.
The care of people with sickle cell disease may include infection prevention with vaccination and antibiotics, high fluid intake, folic acid supplementation and pain medication. Other measures may include blood transfusion and the medication hydroxycarbamide (hydroxyurea). A small percentage of people can be cured by a transplant of bone marrow cells.
As of 2015, about 4.4 million people have sickle cell disease, while an additional 43 million have sickle cell trait. About 80% of sickle cell disease cases are believed to occur in Sub-Saharan Africa. It also occurs relatively frequently in parts of India, the Arabian Peninsula and among people of African origin living in other parts of the world. In 2015, it resulted in about 114,800 deaths.
Signs and Symptoms
Signs of sickle cell disease usually begin in early childhood. The severity of symptoms can vary from person to person. Sickle cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.
Normally, humans have haemoglobin A, which consists of two alpha and two beta chains, haemoglobin A2, which consists of two alpha and two delta chains, and haemoglobin F, consisting of two alpha and two gamma chains in their bodies. Out of these three types, haemoglobin F dominates until about 6 weeks of age. Afterwards, haemoglobin A dominates throughout life. In people diagnosed with sickle cell disease, at least one of the β-globin subunits in haemoglobin A is replaced with what is known as haemoglobin S. In sickle cell anaemia, a common form of sickle cell disease, haemoglobin S replaces both β-globin subunits in the haemoglobin.
Sickle cell conditions have an autosomal recessive pattern of inheritance from parents.
The types of haemoglobin a person makes in the red blood cells depend on what haemoglobin genes are inherited from her or his parents. If one parent has sickle cell anaemia and the other has sickle cell trait, then the child has a 50% chance of having sickle cell disease and a 50% chance of having sickle cell trait. When both parents have sickle cell trait, a child has a 25% chance of sickle cell disease, 25% do not carry any sickle cell alleles, and 50% have the heterozygous condition.
How to manage Sickle cell Disease
Folic Acid And Penicillin
From birth to five years of age, penicillin daily, due to the immature immune system that makes them more prone to early childhood illnesses is recommended. Dietary supplementation of folic acid had been previously recommended by the WHO.
Possible advantage of being heterozygous for sickle cell anemia disease (A) vs. normal blood cell response (B) when infected with malaria.
The protective effect of sickle cell trait does not apply to people with sickle cell disease; in fact, they are more vulnerable to malaria, since the most common cause of painful crises in malarial countries is infection with malaria. It has therefore been recommended that people with sickle cell disease living in malarial countries should receive lifelong medication for prevention.
Blood transfusions are often used in the management of sickle cell disease in acute cases and to prevent complications by decreasing the number of red blood cells (RBC) that can sickle by adding normal red blood cells.
Bone marrow transplant
Bone marrow transplants have proven effective in children. Bone marrow transplants are the only known cure for SCD. However, bone marrow transplants are difficult to obtain because of the specific HLA typing necessary. Ideally, a close relative (allogeneic) would donate the bone marrow necessary for transplantation.
Most people with sickle cell disease have intensely painful episodes called vaso-occlusive crises.Painful crises are treated symptomatically with pain medications; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manage on NSAIDs (such as diclofenac or naproxen).
Psychological therapies such as patient education, cognitive therapy, behavioural therapy and psychodynamic psychotherapy, that aim to complement current medical treatments, require further research to determine their effectiveness.
Acute chest crisis
Management is similar to vaso-occlusive crisis, with the addition of antibiotics (usually a quinolone or macrolide, since cell wall-deficient [“atypical”] bacteria are thought to contribute to the syndrome), oxygen supplementation for hypoxia, and close observation.
Sickle cell anaemia can lead to various complications, including:
- Increased risk of severe bacterial infections
- Chronic kidney failure
- Silent Stroke
- Cholelithiasis (gallstones) and cholecystitis may result from excessive bilirubin production and precipitation due to prolonged haemolysis.
- Avascular necrosis (aseptic bone necrosis) of the hip and other major joints may occur as a result of ischaemia.
- Decreased immune reactions due to hyposplenism (malfunctioning of the spleen)
- Priapism and infarction of the penis.
- Leg ulcers.
- Osteomyelitis (bacterial bone infection).
- Acute papillary necrosis in the kidneys
- In eyes, background retinopathy, proliferative retinopathy, vitreous haemorrhages, and retinal detachments can result in blindness.
- Regular annual eye checks are recommended.
- During pregnancy, intrauterine growth retardation, spontaneous abortion, and pre-eclampsia
- Chronic pain: Even in the absence of acute vaso-occlusive pain, many patients have unreported chronic pain.
- Pulmonary hypertension (increased pressure on the pulmonary artery) can lead to strain on the right ventricle and a risk of heart failure; typical symptoms are shortness of breath, decreased exercise tolerance, and episodes of syncope.