Hereditary spherocytosis is a genetic defect that affects the membrane or covering of the red blood cells, which are small, round and rigid. During circulation, these cells are unable to “squeeze” through small blood vessels called capillaries as well as the spleen, but rather get broken down leading to haemolytic anaemia (normal red blood cells last for 120 days, whereas in HS they last 10 – 30 days).

Anaemia (fatigue, shortness of breath, irritability, dizziness, increased heart rate, headaches) and jaundice are caused when red blood cells break down and release bilirubin, splenomegaly (enlarged spleen) and gallstones.

This results in small, round red blood cells which are rigid and non-deformable and are easily destroyed by the spleen. Almost all patients have an enlarged spleen. A vitamin called Folic Acid should be taken so that the bone marrow can work better to produce more red blood cells. Treatment consists of removing the spleen so that the red blood cells are not destroyed. This should only be done after the age of 6 years when the body’s immunity is fully developed. The child should receive a pneumococcal vaccine prior to the splenectomy and should take the antibiotic Penicillin for life as prevention against infection.

Haemophilia is an X-linked recessive (passed down from a mother to her sons) inherited blood disorder in which the blood does not clot properly due to low or absent clotting factors which work together with the platelets to form a stable clot. The condition can be mild, moderate or severe. There are two types, namely: Haemophilia A or B

Type A

Haemophilia A, also called factor VIII (FVIII) deficiency or classic haemophilia, is a genetic disorder caused by missing or defective factor VIII, a clotting protein. It occurs in boys and is usually passed down from a carrier mother to her sons, but in about 1/3 of cases, there is a spontaneous mutation, a change in a gene. People with haemophilia A often have delayed onset, prolonged bleeding. Their platelets are normal, and therefore they initially stop bleeding. When the platelet pug dissolves and a clot does not form, bleeding occurs. Bleeds can occur internally, into joints and muscles, or externally from minor cuts, dental procedures or trauma. How frequently a person bleeds and the severity of those bleeds depends on how much FVIII is in the plasma, the straw-coloured fluid portion of blood. Normal plasma levels of FVIII range from 50% to 150%. Levels below 50%, or half of what is needed to form a clot, determine a person’s symptoms.

• Mild haemophilia A:  6% – 49% of FVIII in the blood. People with mild haemophilia A generally experience bleeding only after serious injury, trauma or surgery. In many cases, mild haemophilia is not diagnosed until an injury, surgery or tooth extraction results in prolonged bleeding. The first episode may not occur until adulthood. Women with mild haemophilia often experience menorrhagia (heavy menstrual periods) and can haemorrhage after childbirth.
• Moderate haemophilia A:  1% – 5% of FVIII in the blood.People with moderate haemophilia A tend to have bleeding episodes after injuries. Bleeds that occur without obvious cause are called spontaneous bleeding episodes.
• Severe haemophilia A: <1% of FVIII in the blood. People with severe haemophilia A experience bleeding following an injury and may have frequent spontaneous bleeding episodes, often into their joints and muscles.

Type B

Haemophilia B, also called factor IX (FIX) deficiency or Christmas disease, is a genetic disorder caused by missing or defective factor IX, a clotting protein. It also occurs in boys, being passed down from a carrier mother to her sons, but may also be a result of a spontaneous mutation, a change in a gene. (Symptoms are the same as above for Haemophilia A).

This is a genetic disorder caused by missing or defective Von Willebrand factor (VWF), a clotting protein. VWF binds factor VIII, a key clotting protein, and platelets in blood vessel walls, which help form a platelet plug during the clotting process. VWD occurs in both boys and girls. The symptoms are alike to a platelet deficiency with mucosal bleeds (especially nose and mouth), and menorrhagia in girls. 

Treatment

• On demand: Replace the missing factor. Giving treatment to stop prolonged bleeding when it occurs.  The factor is recombinant (made in a laboratory) Factor VIII or Factor IX.
• DDAVP (a synthetic vasopressin) may be given to release VWF from the cells to aid clotting in VWD. However, the patient must be tested first to see if they are a responder to DDAVP.
• Preventative treatment (prophylaxis) for severe haemophiliacs where they are given recombinant Factor VIII or Factor IX regularly twice a week thus preventing bleeding episodes, and subsequent complications, such as joint and/or muscle damage. 

Thalassaemia is one of a group of genetic blood disorders referred to haemoglobinopathies. These disorders, mainly comprising different types of thalassaemia and sickle cell anaemia, are among the most common inherited diseases worldwide: around 7% of the global population carry an abnormal haemoglobin gene, and more than half a million affected children are born each year.

Beta Thalassaemia is an inherited blood disorder where normal haemoglobin (in red blood cells) is unable to be made due to a gene defect. This results in severe anaemia. The word Thalassaemia is of Greek origin, Thalassa (sea) and aemia (blood). Thalassemia occurs in people of Mediterranean origin, the Middle East and the Indian sub-continent.

Medical advances in thalassaemia have changed the natural history of the disease, such that it is now both preventable and treatable – a chronic, rather than a fatal, condition. With appropriate clinical management and healthcare, patients with thalassaemia can lead a near – normal life as integrated, productive members of society. The treatment of thalassaemia is lifelong, complex and can be costly, requiring specialised expertise and a multi-disciplinary approach. The majority of patients, particularly in low-resource countries are children. This is because, without treatment, patients die at an early age. In addition to the struggle faced by patients coping with the disease, thalassaemia has great emotional, social and financial repercussions for families as a whole.

Untreated, most children would die by 1-3 years of age. In addition, the liver and spleen become swollen and the bones of the face and head become deformed. Chronic, regular blood transfusions are required to sustain life. If the haemoglobin is kept in the normal range, then children can lead “normal lives”. However, the result of many transfusions is the over-accumulation of iron in the organs of the body. This leads to heart failure, liver cirrhosis and diabetes. If the iron level in the body is kept low, then patients can live for more than 50 years. Other possible treatments include stem cell transplant and in the future, gene therapy.

Signs And Symptoms

• Most children with Beta Thalassemia Major present with severe anaemia, poor feeding, poor growth and cardiac failure before the age of 1 year. An enlarged spleen may occur.

• If left untreated, the following symptoms present:
  • Anaemia /fatigue /tiredness
  • Slow growth
  • Enlarged heart and cardiac failure
  • Dark urine
  • Jaundice
• Bone problems – the bones become wider than normal, resulting in frontal bossing of the skull bones, a marked overbite of the upper jaw. The bones may become brittle and break easily.
• Enlarged spleen and liver.  (The spleen is tucked under the rib cage next to the stomach on the left side of the abdomen. It’s a soft, spongy organ that performs several critical jobs).            

Complications and Treatment

• Complications:  Iron overload – this leads to conditions such as sugar diabetes, cardiac conditions, liver diseases, infections and osteoporosis.
• Treatment:  Regular lifelong blood transfusions. Iron chelation therapy to prevent iron overload, which is as a result of the frequent blood transfusions, is necessary as iron cannot be excreted from the body normally. Iron can be eliminated from the body by a certain drug called Desferrioxamine. Unfortunately, this must be given by injection under the skin as a continuous infusion with the help of a syringe-driver ‘pump’. Recently, new oral drugs have been developed which are effective and safe and can be given by mouth. However, they are very expensive.

In sickle cell anaemia, the abnormal haemoglobin causes red blood cells to become rigid, sticky and misshapen. The sickle cell gene is passed from generation to generation in a pattern of inheritance called autosomal recessive inheritance where one inherits two mutated genes, one from each parent and these parents do not show symptoms of the disease. It affects both male and females alike. Each red cell contains haemoglobin (which is responsible for the transportation of oxygen to all parts of the body).  The normal red cell contains haemoglobin A and the sickle cell red cells contain haemoglobin S. The sickle haemoglobin causes the red blood cells to become deformed into a sickle shape. This results in ‘sticky’ red blood cells which block small blood vessels and cause painful ‘crises’ in the bones, tummy and chest. More seriously, a stroke may occur when the brain is affected.

It affects millions of people worldwide but is most common among people whose ancestors come from Equatorial Africa, and less commonly Mediterranean countries such as Greece &Turkey, and India.   Most individuals with sickle cell are healthy at birth and become symptomatic later in infancy or childhood. It is suspected in infants and young children with painful swelling of hands and feet, pallor (paleness), jaundice, pneumococcal sepsis or meningitis, severe anaemia.  Usually the spleen is infected early in life and is NOT enlarged. 

Symptoms:

• Anaemia and jaundice
• Infections and fever (especially pneumococcal infections). Children living in endemic malaria areas have an increased susceptibility to malaria.
• Veno-occlusive crises (resulting from the sticky red blood sickle cells blocking small blood vessels). Pain usually occurs in the abdomen, bones and joints. A chest crisis maybe indistinguishable from a chest infection or pneumonia. Priapism may occur in adolescents (painful erection).
• Hypersplenic or Hyper Haemolytic crises may occur in young children, when the spleen suddenly enlarges and the haemoglobin drops to dangerously low levels which may result in death is not transfused immediately.

Complications:

• Cardiac enlargement and cardiac failure due to severe anaemia
• Stroke
• Osteomyeltis (bone infection), and avascular necrosis of the bones (blocked blood vessels and no oxygen to the bone)
• Pulmonary hypertension
• Gallstones
• Poor growth and delayed puberty
• Eye damage, kidney damage
• Leg ulcers

What Can Be Done To Prevent These Complications?

• Health education to caregivers regarding disease process.
• Caregivers should know how to check for fever for the quick treatment of infections.
• Avoid extreme weather conditions; cold or hot.
• Drink adequate amounts of water.
• Take folate (folic acid) daily to help make new red blood cells.
• Take daily prophylactic antibiotic to prevent infections.
• Avoid over-exertion and get plenty of rest.
• Hydroxyurea may be given to increase the amount of foetal haemoglobin in the blood, thus reducing the amount of sickle haemoglobin (HbS). This can prevent veno-occlusive crises, but needs to be taken daily without fail.
• Get regular check-ups from knowledgeable healthcare providers.
  

Treatment During A Crisis

• Child needs to be hospitalised.
• Type of crisis e.g. vaso-occlusive, splenic sequestration, aplastic, haemolytic or acute chest syndrome to be assessed by doctor and treated appropriately.
• Increased alkanalizing IV Fluids to be given.
• Pain to be assessed and adequately treated.
• Blood transfusion, if required.
• Bed rest until the crisis controlled.