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What is sickle cell disease?
Sickle cell disease is an inherited change in the blood. The red colour of the blood is a protein called haemoglobin which transports oxygen from the lungs to the tissues where it is used to produce energy. Normal haemoglobin is called A or HbA and most people inherit this from both parents and are called AA. In sickle cell disease the haemoglobin is chemically different and called S or HbS. Sickle haemoglobin still carries oxygen, but tends to crystallise when the oxygen is released causing the red blood cells to change in shape. When this happens it is difficult for the cells to flow freely in the narrow blood vessels causing blockages which lead to pain and other complications.
Why the name sickle?
This refers to the change in shape of the red blood cell caused by sickle haemoglobin when the oxygen is removed. Normal red blood cells are round and like a doughnut with thicker edge and thinner middle. Sickled red blood cells are long and pointed like a sickle or scythe, used for cutting grass.
How do you get sickle haemoglobin?
It is inherited from your parents. If the abnormality is inherited from one parent it is called the sickle cell trait but if inherited from both parents, it is called homozygous sickle cell (SS) disease or sickle cell anaemia. There is no way you can get sickle haemoglobin except from your parents - you cannot 'catch' it like the ‘flu’ or the measles. It cannot be passed on by sexual intercourse.
What is the sickle cell trait?
It is the carrier state for sickle cell disease when a person inherits one HbS gene from one parent and a normal HbA gene from the other. It is important to know that someone with the sickle cell trait may pass the gene on to their children. If two people with the trait have children, there is a 1 in 4 chance at each pregnancy that the child will inherit sickle cell disease. The sickle cell trait has only 20-40% sickle haemoglobin but not enough to cause complications.
How common is the sickle cell trait?
In Jamaica about 10% of the population have the sickle cell trait but in other islands the frequency varies from 7% in Barbados to as high as 13-14% in Dominica and St. Lucia. This compares to 8% in the Afro-American population, and frequencies of 20-30% in the populations of West Africa and of some populations in Saudi Arabia, India, Greece and Italy.
Is the sickle cell abnormality confined to African populations?
No. The sickle cell trait has become common in many malarial areas of the world. This is because people with the sickle cell trait survive malaria better so that in areas where malaria is common, people with the trait have slightly better health, less chance of dying from malaria, and greater chance of reaching adulthood and passing on the sickle abnormality to their children. In this way the frequency of the sickle cell gene has gradually increased over the centuries in these areas. Equatorial Africa is one of the most highly malarial areas in the world and since the population living in this area is almost entirely Black, the sickle cell trait has become common among Black people. The sickle cell trait was brought to the Caribbean, North and South America by people from this part of Africa.
However, highly malarial areas also occur in Saudi Arabia, Southern India, Greece, and Italy and in all of these countries there are people of different races with high frequencies of the sickle cell trait.
It is important to remember that although people with the sickle cell trait are better able to survive malaria, people with sickle cell disease frequently die if they become infected.
How common is sickle cell disease?
This depends on the frequency of the sickle cell trait. In Jamaica where just over 10% of the population have the sickle cell trait, a case of SS disease occurs in every 300 births. However, in addition to SS disease in which the sickle abnormality is inherited from both parents, there are two other types of sickle cell disease which occur in the Caribbean.
Haemoglobin C is another chemically different haemoglobin which occurs in 3-4% of people in the Caribbean. When inherited from only one parent it is called the haemoglobin C (Hb C) trait and causes no problems but when HbS is inherited from the other parent, this results in sickle cell-haemoglobin C (SC) disease which occurs in 1 out of every 500 births in Jamaica.
The beta thalassaemia trait is a condition where the structure of haemoglobin is usually normal but production is deficient. Inheritance of the beta thalassaemia gene from one parent and of the HbS gene from the other results in 2 principal types of condition called sickle cell-beta thalassaemia and the difference is important. If the beta thalassaemia gene is betao, there is no normal HbA produced and the condition is generally severe. If the beta thalassaemia gene is beta+, there is usually 20-30% HbA which inhibits sickling and the condition is generally mild. The betao thalassaemia gene occurs in 0.5% and the beta+ thalassaemia gene in 1% of people in the Caribbean. In Jamaica, sickle cell- beta+ thalassaemia occurs in every 3,000 births and sickle cell- betao thalassaemia in every 7,000 births. Adding these all together, 1 in every 150 births in Jamaica has a form of sickle cell disease.
How can you find out if you have sickle haemoglobin?
This can only be done by a blood test in a laboratory equipped to do a test called haemoglobin electrophoresis; simply having a sickle or solubility test does not make the vital distinction between the harmless trait and forms of sickle cell disease. Electrophoresis must be carefully carried out to avoid confusion with other abnormalities. Other special tests are available but electrophoresis has been adequate in the Caribbean
Why does sickle haemoglobin cause problems?
The chemical change in sickle haemoglobin (HbS) affects the protein in such a way that when oxygen is removed, molecules of HbS tend to stick together producing long cables or filaments which deform the red cells to the sickle shape. The abnormal shape and increased rigidity of these sickled cells leads to a tendency to block the flow in small blood vessels and to their destruction. These two processes lead to the main problems of sickle cell disease.
The increased blood destruction leads to anaemia and the increased production of bilirubin results in jaundice and the formation of gallstones. Obstruction of blood flow in small blood vessels produces tissue damage and pain and may occur anywhere in the body but especially in the bones, lungs, brain, eyes, and spleen.
Do problems occur in the sickle cell trait?
Problems rarely occur in the sickle cell trait. People with the trait are healthy and may never know that they have it. Problems may develop in the sickle cell trait if the blood oxygen level is low as occurs with suppression of breathing following anaesthetics, or the overuse of drugs or alcohol, or when there is a shortage of oxygen in the air as at high altitudes.
Sickling may occur in the kidney where there is reduced oxygen causing haematuria (blood in the urine). The frequency of these problems in people with the trait is unknown and generally no special treatment or observation is necessary in the sickle cell trait. The greatest importance of the trait is that when somebody with the trait has children with somebody who also has the trait then there is a one in four chance of each child having SS disease.
What are the symptoms of sickle cell disease?
These vary with the age of the patient. Problems may start in childhood and include a painful swelling of the fingers or toes (dactylitis or the hand-foot syndrome), sudden swelling of the spleen which traps the red blood cells causing a sudden severe anaemia (acute splenic sequestration), overwhelming blood infections especially caused by a bacteria called Streptococcus pneumoniae (pneumococcal septicaemia), severe anaemia associated with a virus infection (aplastic crisis), a complex ‘pneumonia-like syndrome (acute chest syndrome), and stroke. In later childhood and adolescence, painful crises and leg ulcers become important and there is also delay in physical and sexual development. In later adult life, there may be accumulated damage in the lungs (pulmonary fibrosis) and kidney (chronic renal failure).
Dactylitis or Hand-Foot Syndrome: A painful swelling of the fingers, toes, back of the hand or foot affecting one or multiple sites. Typically starts from 3-6 months and may be the first manifestation of sickle cell disease. Frequently recurrent and ceases around the age of 5 years. Usually resolves completely but rarely, secondary infection may cause permanent damage and shortened fingers or toes.
Acute Splenic Sequestration: A sudden enlargement of the spleen, an organ under the left ribs which may be felt through the skin, which is associated with the trapping of blood within the spleen and an acute, sometimes life threatening anaemia. May start as early as 3 months and becomes uncommon after 5-6 years. Often recurrent and treatment consists of early detection, transfusion if necessary, and removal of the spleen with recurrent attacks. Teaching parents to feel for the spleen everyday has allowed early detection and treatment and has reduced mortality from this complication by 90%.
Pneumococcal Septicaemia: The spleen is damaged by circulating sickle cells and loses its ability to remove bacteria that may have got into the blood. In non-malarial areas, the most common bacteria is Streptococcus pneumoniae and infection with this may cause high fever, brain damage and death. Infections may be prevented with special vaccines and regular penicillin which should be started as early as 4 months and continued at least until 4 years. The risk of these infections is reduced at later ages.
Aplastic Crisis: In this condition, the bone marrow suddenly stops working and the haemglobin level falls by 1g/day and may reach life threatening levels. It is caused by a specific virus and occurs in epidemics. Treatment consists of blood transfusion. Patients never have more than one attack of this complication which becomes uncommon after the age of 15 years.
Acute Chest Syndrome: A complication with fever, chest pain and cough associated with lung changes on X-ray, which is a common and serious problem in sickle cell disease. Treatment usually requires antibiotics and regular transfusion may be used to prevent recurrent attacks.
Stroke: Damage to the brain from blocked blood vessels may cause strokes in childhood. Treatment is complex and largely consists of prevention by early detection of vessel blockages and of repeat attacks by chronic blood transfusion. Affected children may lose the ability of normal movement in the affected limb and may have fits.
Growth: Growth and sexual development of children with SS disease is usually slower than normal but by early adult life they catch up with normal people. Even as adults, some people with SS disease tend to be thin. It is important to realise that this delay in development and thin body stature is normal for SS disease and there is no reason to spend money on expensive tonics.
Painful Crises: Often severe pains caused when sickled blood cells do not pass freely and block blood vessels, starving the affected areas of oxygen. These pains can occur in the joints, abdomen or back and may be very severe, usually associated with fever and red urine. The painful crisis is a characteristic feature of sickle cell disease.
Painful crises are often started by:
- Over-exertion, causing extreme fatigue or dehydration.
- Getting cold, or wet.
- Sudden temperature changes e.g. from a hot atmosphere to a cold air conditioned room.
- A prolonged infection e.g. a chest cold, or sinusitis.
- Stress/emotional upset.
- Dehydration from not drinking enough.
Circumstances known to bring on attacks should be avoided. Treatment consists of tablets or injections to control the pain, and plenty of fluid by mouth.
Jaundice: As sickle cells break down at a faster rate than usual, excess bilirubin builds up in the system. This bilirubin, or yellow pigment, shows in the eyes, skin, and sometimes causes darker urine. Jaundice is often more pronounced during painful crises or can indicate that a crisis is about to start.
Skin ulcers: People with sickle cell disease are prone to leg ulcers around the ankles. Some occur spontaneously, although many are the result of a cut or bruise. Ulcers often take a long time to heal and frequently recur. The skin around the ankles has a poor blood supply. In patients with sickle cell disease, the sickled cells can block these blood vessels and slow the healing process. Children should not be kept away from school because of the ulcers. Patients with ulcers may need injections against tetanus and careful follow-up. Incompetence of the leg veins is common and tight elastic bandages or support stockings may improve healing of ulcers.
Are people with sickle cell disease always anaemic?
No. People with SS disease are usually anaemic with haemoglobin levels between 6-9 g (compared with normal values of 12-15 gms). In SC disease, the haemoglobin level varies from 8-15 g and so may be quite normal. The degree of anaemia in sickle cell disease is not usually dangerous and rarely causes problems. It is not helped by iron medicines which should not be taken.
Is the jaundice in sickle cell disease catching?
Jaundice (yellow eyes) is common in SS disease and usually not due to liver disease, a cause of jaundice in the normal population. It is due to the rapid breakdown of blood cells. Jaundice may increase during fever or the painful crisis. If the yellowness becomes very marked, patients may have developed a liver problem or gallstones could have blocked the outflow from the liver. In such cases, patients should visit their doctors for a careful check-up.
What about pregnancy in sickle cell disease patients?
Patients with SS disease can get pregnant but are more likely to lose the baby during pregnancy. It is most important that patients have regular antenatal care and deliver their babies in hospital. Although many patients manage pregnancy without problems, painful crises and acute chest syndrome are common especially in late pregnancy. Patients with sickle cell disease should consider carefully whether they wish to become pregnant.
Can sickle cell patients take family planning?
Yes they can and should - until they are ready to have children. It is common belief that sickle cell patients should not take family planning but this is quite wrong. The risks during pregnancy are certainly greater than any risks of family planning. The best method of reliable contraception is the 3-monthly injection (Depoprovera) because it improves other aspects of sickle cell disease. The pill is most widely used but intra-uterine devices (the coil) and condoms are commonly used. There are so many methods of family planning available today.
Do all types of sickle cell disease have the same problems?
Yes, but most problems are more common and more severe in SS disease and sickle cell- betao thalassaemia and less common in SC disease and sickle cell- beta+ thalassaemia. Many people with SC disease and sickle cell- beta+ thalassaemia are so mildly affected that they never know that they have a disease and occasionally even SS disease may be very mild.
Can sickle cell disease be prevented?
Yes. It is easy to detect the sickle cell trait and if a person with the trait avoided having children with another person with the trait, there would be no more cases of SS disease. If everybody knew this and blood tests to detect sickle haemoglobin were easily available then people could make decisions on having healthy children and on the size of their families.
Can sickle cell disease be treated?
Yes. Most people with sickle cell disease have good health most of the time, and treatment is given for complications as they occur. Regular immunisation and good nutrition will make young patients less susceptible to infections, and easy access to medical care will ensure that complications are treated correctly and promptly as they occur. A regular medical check up is important. Folic acid may assist blood formation and perhaps improve growth. Blood transfusions are not required except when the haemoglobin level is markedly below the patient's usual level. Regular attendance at the doctor is important since they may be able to detect things going wrong and treat them early.
Can sickle cell disease be cured?
Yes, but only with a bone marrow transplant from a person without sickle cell disease. Remember, it can be prevented if persons with the sickle cell trait avoid having children with others who have abnormal haemoglobin genes.
What is the outlook for someone with sickle cell disease?
Generally much better than in the past. Many descriptions of the disease were based only on seriously ill patients in hospital, while mild cases of the disease remained unrecognised in the community. It is now known that in the Caribbean there are many patients with the disease who may never visit hospital and the true picture of sickle cell disease must include these as well as seriously affected patients. Furthermore, there is evidence that the disease is becoming less serious with the improving socio-economic conditions in the Caribbean. Survival beyond the age of 30 years used to be considered unusual in SS disease but now many people live beyond this age and patients over 60 years are not uncommon.
It should be remembered that most patients with sickle cell disease have reasonable health for much of the time and only occasionally do serious complications or crises occur. The period of greatest risk is early childhood and to provide special observation and treatment during this period, the diagnosis must be made at birth. Regular observation and access to physicians with specialized knowledge and therapy in sickle cell clinics may also allow early detection and treatment of complications.
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