The Thalassaemias are blood disorders, so we have to describe blood and its functions before we can talk about thalassaemia
Blood is a part of your body. It is pumped by your heart, and circulates in the blood vessels that spread it through your whole body. It gives out the oxygen and food it is carrying to the tissues of the body, and picks up waste to take away
Blood is made up of a light yellow liquid, called plasma, and cells which float round freely in the plasma. There are 3 types of blood cells: red cells, white cells and platelets.
Each part of the blood has its own special function. The plasma carries water, salts and materials such as food, hormones and drugs to your tissues, and carries away wastes, to be got rid of through your lungs (in your breath) and through your kidneys, in your urine.Your white blood cells defend your body against infections. Your platelets stop losing blood if you hurt yourself. They stick together and block up your blood vessels when they get damaged, so they stop any more blood escaping. You have many more red cells than white blood cells. The red blood cells are full of haemoglobin, which is red, and this is what makes your blood look red. Hemoglobin picks up oxygen from the air in your lungs, and carries it round to your tissues, where it lets it go. To live, your tissues need to breathe, so they need oxygen. New red blood cells are being made all the time in your bone marrow. They only live about 120 days. Then they are destroyed in your spleen.
If you have too few red blood cells, or there is too little haemoglobin in them, you have “anaemia”. This simply means a shortage of blood. If the anaemia is mild. it does no harm and you may not even notice it: but if it is severe, you are ill. because your tissues don’t have enough oxygen. The commonest form of anaemia is “iron deficiency” anaemia:. This can happen if you don’t have enough iron in your diet. It can be cured by taking medicines. Thalassaemia is quite different from iron deficiency anaemia. It is an inherited anaemia. It cannot be cured by taking medicines. Thalassaemia is an inherited disease of the blood. The patient does not produce enough haemoglobin so it causes anaemia and requires specialized treatment.
Every characteristic of your body is controlled by “genes,” which control your growth and all your physical functions. Genes are present in every cell of your body. You have two of every kind of gene, one passed on from your mother, the other passed on from your father. Among many other genes, you have two genes that control how haemoglobin is made in each of your red blood cells.
Normal “people are normal because they have two normal genes for haemoglobin.
Healthy carriers of ß-thalassaemia trait have one normal gene for haemoglobin and the other diseased. They are healthy because one gene is working well. Since one gene is inherited from each parent, at least one of the parents must be a carrier.
People with ß-thalassaemia major have both diseased genes for haemoglobin, one inherited from each parent, so both the parents must be carriers.
Children are conceived when a sperm from the father meets an egg from the mother. Eggs and sperms are made so that they carry only one of each gene from each parent. When the sperm and egg meet and become one, the material the baby will be made from has two genes for every characteristic (one from the mother and one from the father.)
The eggs or sperm from normal people always carry normal genes for haemoglobin, and so cannot transmit thalassaemia. When healthy carriers of thalassaemia produce eggs or sperm, each egg or sperm carries either a normal gene or a thalassaemia gene, but not both, so half the eggs are thalassaemic and half are normal; and half the sperms are thalassaemiac and half are normal.
They cannot pass on thalassaemia trait or thalassaemia major to their children as they carry normal genes.
The children will inherit a normal gene from the “normal” parent. However, they may inherit a normal or a thalassaemia gene from the carrier parent. For each child there is a one in two (50%) chance of inheriting the thalassaemia gene from the carrier parent: if this happens, the child will have thalassaemia trait. There is also a one in two (50%) chance of inheriting the normal gene from the carrier parent: if this happens the child will be completely normal. None of this couple’s children can have thalassaemia major.
When the mother produces an egg (once a month) the egg is either completely normal or thalassaemic. There is no way of telling in which order thay will come. And when the father produces sperm half are normal and half are thalassaemic. When the mother produces a normal egg, it does not matter what kind of sperm fertilizes it. If the normal egg is fertilized by a normal spem, the child will be completely normal. If the normal egg meets a thalassaemic sperm, the child will be a healthy carrier.
But it the mother produces a thalassaemic egg, it matters very important what kind of sperm meets it. If the sperm is normal, the child will be a healthy carrier of thalassaemia. But if the thalassaemic egg is fertilized bay a thalassaemic sperm, the child will have thalassaemia major. This is why couples of carriers have a one in four (25%) chance in each pregnancy of having a child with thalassaemia major; a one in two (50%) chance of having a child with thalassaemia trait; and a one in four (25%) chance that the child will have normal gene from both parents, and so will be completely normal.
These chance are the same in each pregnancy which may or may not be repeated.
In the last
During pergnancy, thalassaemia major does not affect the foetus. This is because the foetus has a special sort of haemoglobin, called “foetal haemoglobin” (HbF for short). Children and adults have a different haemoglobin called ” adult haemoglobin” (HbA for short). When a baby is born, most of its haemoglobin is still the foetal kind, but during the first 6 months of life it is gradually replaced with adult haemoglobin. The problem with thalassaemia, is that the child cannot make enough adult haemoglobin. Therefore childrren with thalassaemia major are well at birth, but usually become ill before they are 2 years old. They usually become quite anaemic (their haemoglobin level is usually less than 55% (8 g/dl). So they become pale, do not grow as well as they should, and often have a big spleen. The number of months that can pass before a thalassaemic child becomes ill can differ quite a lot from case to case. This is because thalassaemia can be caused by several different defects in the haemoglobin genes. However, nearly all children with severe ß-thalassaemia become ill by 4 years of age, and need blood transfusions.
The anaemia gets worse, the child stops growing altogether, and the spleen goes on getting bigger, so the abdomen gets very big. The bone marrow, the tissue that forms the red blood cells, expands inside the bones because of this. But its efforts to make more and more red blood cells are useless. The red cells it makes do not contain enough haemoglobin, and most simply die without ever getting out of the bone marrow. However, the marrow’s effort to expand makes the bones weak and alters their shape. The cheek bones and the bones of the forehead begin to bulge and the child’s face gets a characteristic look, so that people can see from a distance that something is wrong. The spleen’s normal job is to destroy old red blood cells in the circulation, but as time passes it begins to destroy young red blood cells as well. Finally it also kills white blood cells and platelets. This is called “hypersplenism”. So in the end, the spleen makes the child’s illness worse.
The traditional treatment consists of :
1. Blood transfusion
2. Removing the spleen (Splenectomy)
3. Chelation treatment (Desferal etc)
To be precise, the treatment is not blood transfusion, but transfusion of red blood cells. Thalassaemic are only short of red blood cells: they make the other parts of the blood quite normally, so only red blood cells should be transfused. (other parts of blood can be used for patients having other diseases). The normal haemoglobin level for women and children is 77-100% (11-14 g/dl). So thalassaemics should be transfused when the haemoglobin is around 70%, and the haemoglobin should be raised to around 100%. (or, in grams, they should be transfused at about 10g/dl, and the haemoglobin should be raised to about 14g/dl). To do this it is initially necessary to give a transfusion about every 4 weeks, which:-
(a) It corrects your anaemia, and makes sure that your tissues get normal amount of oxygen. This allows you to live and grow normally.
(b) It lets your bone marrow rest, so that your bones can develop normally and will be strong, and your face looks normal.
(c) It slows down, or prevents, any increase in the size of your spleen.
When the spleen becomes too active and starts to destroy normal red blood cells, transfusions becomes less and less effective. Then it may become necessary for a surgeon to take the spleen out. This operation is called splenectomy.
Every 400ml of blood transfused contains about 200 milligrams of iron. Packed red cells. have 200mg of iron per 200-250 ml of blood. This iron can’t be taken out of the blood because it is part of the haemoglobin, which your body needs. On its own, your body can only get rid of a tiny amount of iron, so if you have transfusions regularly, iron gradually accumulates in your body. It is stored in certain organs, especially the liver, the heart, and the endocrine glands. Your body can store a lot of iron safely, but in the end it can damage the organs where is is stored. Fortunately, there are drugs that can pick up the iron, and carry it out of your body in your urine and feces. The only one that is used regularly at present is desferrioxamine, which is also called “Desferal”. If you use Desferal regularly, you can keep the amount of iron in your body down to safe level. Recently oral chelation agents have been developed and are being widely used.
A well- treated patient is quite different from the untreated. There is no anaemia, growth is normal, and the face and the bones look normal. A properly treated patient can have a normal family life and, become a useful member of the community.