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Blood disorders

Blood disorders seen in cases recorded on the CARIS database include :

There are other congenital disorders which affect the blood and although relatively common, do not often appear as cases on the database. This is because they do not appear until adulthood or late childhood, and so are often not reported into CARIS. An examples of this is haemochromatosis .

Blood cells start to develop during the third week of pregnancy but blood formation starts properly during the fifth week in the liver, and later during pregnancy in the spleen, bone marrow and lymph nodes. Three kind of blood cells form about 45% of the blood tissue, these are red blood cells (erythrocytes), white blood cells (leukocytes) and platelets (thrombocytes). Blood disorders include conditions that affect both red and white blood cells, platelets, bone marrow, and the blood constituents involved in clotting or bleeding.

Sickle Cell Disease

What is it?

Sickle cell disease (SCD) is a group of inherited blood disorders, which occur when abnormal haemoglobin occurs in the red blood cells. The most common type of SCD is sickle-cell anaemia. Red blood cells that contain normal haemoglobin are disc shaped. This shape allows the cells to be flexible so that they can move through large and small blood vessels to deliver oxygen. In sickle cell disease, the haemoglobin forms stiff rods within the red cell, changing it into a crescent, or sickle shape. These cells are not flexible and can stick to vessel walls, causing a blockage that slows or stops the flow of blood and as a result oxygen. This can cause a sickle crisis with severe pain. It can also cause infection and organ damage. Normal red blood cells live about 90 to 120 days, but sickle cells last only 10 to 20 days. As a result anaemia is common. Exacerbation of sickle cell disease can be caused by dehydration,  infections, stress, extremes of temperature or even changes in altitude.

What are the genetics, is it hereditary?

Yes - babies born with sickle cell disorder inherit two abnormal haemoglobin genes, one from each parent. When a person has two haemoglobin S (HbS) genes,  the disease is called sickle cell anaemia.  Where a person has only one HbS gene alongside a ‘normal’ haemoglobin gene (HbA) they are said to have sickle cell trait (HbAS) and their health is not adversely affected by this. However there is a one in four chance that should they have a child with another person who also has sickle cell trait the baby will be born with sickle cell anaemia (HbSS). For more information on inheritance, the Sickle Cell society website contains useful information.

How is it detected?

In the antenatal period women are offered screening for sickle cell disorder if their responses to a questionnaire indicate they may be at higher risk of sickle cell disorder. Those at higher risk include women whose country of origin or ancestry includes Africa, Caribbean, Mediterranean, India, Asia and the Middle East.  If a woman is found to be a carrier then the father of the baby is screened. If he too is a carrier then the woman is offered testing to determine the status of the baby. This could be either chorion villus sampling or amniocentesis. For more information see the antenatal screening website

All newborn babies in Wales are tested for sickle cell disease as part of the newborn bloodspot screening. A small sample of blood is taken from the baby’s heel, ideally on day five of the baby’s life, and tested for a number of conditions including sickle cell disease.  More information can be found on the newborn bloodspot  screening website

What is the outlook?

Early identification with antenatal screening or newborn bloodspot screening means that affected babies can receive early preventive treatment including immunisations and antibiotics to mitigate against serious illness. Sickle cell disease  is a life long illness with life expectancy greatly improved over the last 30-40 years with careful management.

How common is sickle cell disease in Wales?

The Public Health Wales screening division suggest a UK prevalence of sickle cell disease as 1/2,000 live births, however there is much lower prevalence in Wales than in some other parts of the UK. There is greater prevalence of sickle cell disease where communities are more ethnically diverse, so it is seen more often in towns and cities than in rural areas. 27 cases of sickle cell disease are recorded on the CARIS database, an average rate of 0.4/10,000 total births.

There are obviously more carriers of the disease than people with the disease, and Orphanet estimates that prevalence of carriers across Europe as 1/150.

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What is it?

Thalassaemia is the name for a group of conditions which, like sickle cell disease, affects haemoglobin.  In these conditions, too little or no haemoglobin is produced by the body. The condition can lead to people having too much iron in their bodies, and they may also be anaemic and more prone to infections.

Thalassaemia is caused by a defect in the protein chains that make haemoglobin. There are two alpha and two beta chains. Thalassaemia is classified according to which chain of the hemoglobin molecule is affected. In alpha-thalassaemia (α-thalassaemia) production of the α globin chain is affected, while in beta-thalassaemia (β-thalassaemia) production of the β globin chain is affected. The most severe type of thalassaemia is beta thalassaemia major, and people with this condition cannot produce normal red blood cells and do not produce enough haemoglobin. Other types include haemoglobin H disease.

The beta globin chains are encoded by a single gene on chromosome 11 and alpha globin chains are encoded by two closely linked genes on chromosome 16. Thalassaemia is most common among people of Mediterranean, south Asian, or Middle Eastern descent, with males and females having very similar rates of disease. It is also possible to be a carrier of the condition (thalassaemia trait).

Is it inherited?

Yes, like sickle cell disease it is an autosomal recessive gene resulting in varying degrees of severity depending on the parents contribution.

How is it detected?

Antenatal screening Wales offers all pregnant women screening for thalassaemia. If the mother is found to be a carrier then this can be passed on to the baby but only as a carrier. If both parents are carriers then the inheritance is similar to sickle cell disorder with a 1 in 4 chance of the baby being born with thalassaemia. It is not screened for at birth with the newborn bloodspot screen.

What is the outcome?

Children born with thalassaemia usually develop symptoms a few months after birth, however less severe types of thalassaemia may not become obvious until later on in childhood. Carriers have no symptoms.

Anaemia is a significant problem for people with the condition and regular blood transfusions are needed by those affected . Lifelong treatment to stop iron building up to harmful levels after multiple blood transfusions is usually needed. This is known as chelation therapy. The overload of iron in the body can cause complications for major organs, bones and hormones, which are associated with possible heart failure, osteoporosis and delayed or incomplete puberty.

These complications are also associated with an increased risk to both mother and baby during pregnancy, with a higher risk of maternal cardiomyopathy and diabetes as well as fetal growth restriction. Most women with thalassaemia will also require ovulation induction therapy to achieve pregnancy.

How common is thalassaemia in Wales?

Thalassaemia is rare in Wales, and on average, only one case per year is reported to the CARIS database. A total of 25 cases have been reported to the database in Wales between 1998 and 2015, giving a rate of 0.4/10,000 births. Worldwide, exact prevalence is unknown. However Orphanet, the online portal for rare diseases gives estimated prevalence worldwide of beta-thalassaemia as 1/100,000, and estimated prevalence of alpha-thalassaemia in northern Europe as the same.

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Hereditary Spherocytosis

What is it?

Hereditary spherocytosis (HS) is an inherited condition affecting red blood cells, and the condition can be mild, moderate, or severe. In HS,  red blood cells change shape to become more sphere-shaped (spherocytic red blood cells) as the surface membrane is less stable.

The change in shape makes it more difficult for the red blood cells to travel around the body, and more prone to rupture. Spherocytic red blood cells are easily destroyed and may last for only a few days, compared to 120 days for normal red blood cells. The destruction of the abnormal red blood cells takes place in the spleen. This abnormal breakdown of red blood cells can lead to a form of anemia called haemolytic anaemia. This can in turn lead to jaundice because of an increase in circulating bilirubin produced during haemolysis.

What are the genetics?

Hereditary spherocytosis is an autosomal dominant or recessive trait, most commonly (though not exclusively) found in people of northern European descent, although an estimated 25% of cases are due to spontaneous mutations. A parent has a 50% chance of passing the mutation onto each of his/her offspring.

How is it detected?

Antenatal screening for HS is not part of the antenatal screening programme in Wales but there is potential for an antenatal diagnosis using cordocentesis and examining the morphology of the fetal blood cells. Severe anaemia can present antenatally as hydrops which is easily identifiable with ultrasound.

Neither is screening for HS part of the newborn bloodspot screening. But severe HS can present as jaundice in the neonatal period,  occasionally requiring exchange transfusion, and in these instances should be possible to diagnose while a baby is still very young.

What’s the outcome?

Most children born with HS have a mild form of the disease, which does not interfere with their lifestyle. However children born with severe hereditary spherocytosis (about 5% of HS cases) are constantly anaemic, and may be transfusion dependent, especially in early life. They may benefit from erythropoietin treatment, and this might reduce the need for transfusions in the first year of life. After the first few years regular transfusion is rarely needed as most children can tolerate a low haemoglobin level.

Haemolysis is associated with an increased risk of gallstones.  Splenectomy may be necessary because of the increased turnover of red cells and accompanying  this, there is a higher risk of contracting infections so it is important for children to have all the recommended vaccines in line with national guidance on immunisation.

How common is hereditary spherocytosis  Wales?

Orphanet suggests that prevalence in northern Europe could be as high as 1 / 2,000 but this includes extremely mild and sub-clinical forms of the disease. 68 cases were registered on the CARIS database by the end of 2015, giving a rate in Wales of 1.1/10,000 births.

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What is it?

Haemophilia is an inherited condition that affects the blood’s ability to clot.  There are two main types, haemophilia A and haemophilia B.  Haemophilia A is due to a deficiency in clotting factor VIII and is the most common type of haemophilia. Haemophilia B is due to a deficiency in factor IX. A third type – haemophilia C  is due to a deficiency in factor XI, and is a more rare and milder form and unlike the other forms of the disease, is not characterised by spontaneous bleeding and does not lead to bleeding in the joints.  In both haemophilia A and B, the deficiency causes a prolonged bleeding time even after minor injury.

What are the genetics?

These are X-linked recessive disorders and so are more likely to occur in males than females. This is because females have two X chromosomes while males have only one, so the defective gene is guaranteed to manifest in any male who carries it. Because females have two X chromosomes and haemophilia is rare, the chance of a female having two defective copies of the gene is very remote, so females are almost exclusively asymptomatic carriers of the disorder.

Congenital haemophilia affects all ethnic groups, and has a worldwide distribution, although haemophilia C is found predominantly in people of Jewish Ashkenazi decent.


No antenatal or postnatal screening tests exist.

What’s the outcome?

Children with mild to moderate haemophilia may not have any signs or symptoms at birth. Their first symptoms are often multiple and large bruises from frequent bumps and falls as they learn to walk. Although there is no cure for haemophilia, it can be controlled with regular infusions of the deficient clotting factor, i.e. factor VIII in haemophilia A or factor IX in haemophilia B. Factor replacement can be either isolated from human blood serum, recombinant or a combination of the two. Gene therapy offers a possible treatment and trials have been encouraging.

Since effective treatments became available,  life expectancy has increased significantly. 

How common is haemophilia in Wales? 

It is estimated that in boys, internationally, 1/5,000 will be born with haemophilia A, and 1/30,000 will be born with haemophilia B. There is a small risk that girls can be born with the condition if both parents carry the gene. Between 1998 and 2015 there were 39 cases of haemophilia A recorded on the CARIS database, and 5 cases of haemophilia B, so slightly fewer than might be expected. This could be because not all cases are reported to the CARIS database.

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Von Willebrand Disease

What is it?

Von Willebrand disease is the most common hereditary blood clotting disorder and 3 types of the disease have been identified, with type 3 being the most severe. It is caused by either a deficiency in Von Willebrand factor, which is a blood protein, or the protein does not work properly. Von Willebrand factor is required for platelet adhesion, and is named after the Finnish physician who first described the disease in 1926. Von Willebrand Factor also carries and protects another clotting factor - Factor VIII.

Von Willebrand disease can cause bruising with minimum trauma, nosebleeds and bleeding gums. Women with the condition may have heavy periods and experience increased blood loss during childbirth.

What are the genetics?

The gene involved is located on chromosome 12. There are 3 types with type 1 and 2 being inherited as dominant and type 3 (the more severe) as recessive.

Management and outcome

Desmopressin is used to stimulate von Willebrand factor and is used for minor trauma or to prepare for dental procedures. It is not used in certain types of the disease. Tranexamic acid is also useful to reduce bleeding.  If surgery is scheduled, certain factor V111 concentrates which contain von Willebrand factors may be used as a precaution.


Routine screening for Von Willebrand disease is not part of the antenatal or neonatal screening programme. It may only be diagnosed in women when they start menstruating and have investigations for heavy periods.

How common is Von Willebrand disease in Wales?

The prevalence is internationally is thought to be about 1 in 100 but many people do not have any symptoms and are never diagnosed with the condition. Prevalence of the most severe form, type 3, is much lower, and has been estimated in various studies as between 1 to 3 per million population, although higher in populations where consanguineous marriages are more common. People with blood type O have levels of Von Willebrand factor about 25% lower than the rest of the population.  About 80% of all cases are type 1.  While it occurs with equal frequency in males and females, women may be diagnosed more often as they may present with heavy / painful periods or excess bleeding during childbirth.

Only 34 cases were recorded on the CARIS database between 1998 – 2015, far fewer than expected, which suggests not only under-reporting of the condition to CARIS, but also many, many cases go undiagnosed.  Additionally there are UK guidelines recommending that children should not be routinely tested for the disease before the age of 6 months, because there are natural changes in the presence of Von Willebrand Factor in the blood in the early months of life.

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