What are the effects and signs?
The symptoms and course of sickle cell disease is very variable between individual children. In some, the abnormality of the blood has few adverse effects and the diagnosis is made by chance during routine blood tests. Other children have mild to moderate anaemia (a low red cell count) but function normally most of the time. Others experience frequent painful crises, have debilitating anaemia and develop serious complications.
Sickle cell disease causes episodes of acute illness called crises that will usually be managed in hospital. Over time the cumulative effects of crises lead to chronic disability because of the tissue damage and loss of organ function that they cause.
In this guidance the acute and chronic effects will be considered separately.
Acute Effects
Sickle cell crises cause episodes of pain affecting the abdomen, chest, back and limbs accompanied by fever, vomiting and malaise. The pain may be severe, the child is unwell, they may have jaundice and are confined to bed for a few days. During the crisis a child will become more anaemic than usual. Some children may develop severe anaemia of such rapid onset that an emergency blood transfusion is needed.
Children with sickle cell anaemia are prone to infections, and crises may be precipitated by a minor infection such as a cold. Infections may rapidly become severe leading to pneumonia, meningitis, osteomyelitis (infectious inflammatory disease of bone) or septicaemia (generalised blood poisoning). These infections may be life threatening.
Sudden and severe damage to the lungs may occur during a crisis and the body is unable to receive sufficient oxygen. This is known as an acute chest syndrome and presents with fever, chest pain and shortness of breath. Acute chest syndrome is a major cause of sudden death, especially in children.
The nervous system may be affected during a crisis leading to seizures, bleeding into the brain (cerebral haemorrhage) or stroke. Children are at highest risk of stroke, around 8-10% of children with sickle cell will have had a stroke. High risk children can be identified using trans-cranial Doppler screening (ultrasound of the blood vessels in the brain). Those at highest risk are put on a blood transfusion programme and this reduces the risk of a stroke happening. Those on a regular transfusion programme will develop the problems of iron overload if not treated preventively with iron chelation therapy. In children who have had a stroke the effects are devastating with both physical and mental disability. Children who have had a stroke and are now “physically recovered” are often left with severe neuro-cognitive defects and have learning disabilities.
Sickle retinopathy (a visual impairment) is caused by the development of new fragile blood vessels in the retina, these can result in retinal bleeds which can present as floaters in the eye or in more severe cases as a retinal detachment due to a severe bleed. This can result in significant damage to the vision and in some cases blindness. The smaller bleeds can be managed with laser therapy to the retina but the retinal detachment cannot be corrected.
Between Crises
In many children the symptoms of the crisis resolve with appropriate treatment and the child returns to normal after seven to ten days. Some children are persistently anaemic between crises with haemoglobin levels between 50 – 70% of normal. (Normal haemoglobin level 11.4 – 15.5 g/dl). In some children this will cause few symptoms because their body has adapted to functioning with low haemoglobin. In others it will cause fatigue and shortness of breath on exertion. Over the years children who have frequent crises, and those with more severe anaemia, will experience poorer health overall. These children are most likely to develop long-term disabling complications.
Long-term complications
- Arthritis - The head of the femur (thigh bone), that forms part of the hip joint, may be severely damaged (avascular necrosis) during a sickle crisis. The hip joint becomes very painful on movement and ultimately severe arthritis of the hip develops. Joint movement will become very restricted and walking is limited. Avascular necrosis may also occur in the shoulder joint causing pain, deformity and restricted upper limb function. Severe arthritis of the hip or shoulder joint occurs at a relatively young age, and the joint requires artificial replacement. This will be seen in adolescent children and is unusual in younger children
- Risk of infection - Abnormalities of the spleen occur. One of the roles of the spleen is to remove red cells, which have a normal life span of about 120 days, from the circulation. In sickle cell anaemia excessive numbers of ‘sickled’ cells accumulate in the spleen causing enlargement of the organ in childhood. Ultimately the normal structure of the spleen is affected, shrinking in size and its functions become impaired. The normal spleen plays a role in protecting the body against infection. As a result the child with sickle cell anaemia is more prone to infections and more likely to develop serious infections. The commonest cause of death in children below the age of 5 years is infection.
- Breathing difficulties - Repeated damage to the lungs leads to chronic pulmonary hypertension, a condition that causes progressive shortness of breath and may lead to heart failure. This condition takes time to develop and is more common in adolescents than young children.
- Kidney failure - Over the years, permanent damage to the blood supply of the kidneys causes impaired renal function that may lead to renal failure.
- Cognitive impairment - Related to ‘silent’ infarcts (resulting from obstruction of circulation) this is present in 20% of adults with sickle cell. This is will result in difficulty in understanding or undertaking specific tasks and can result in relatively simple things like counting or reading becoming difficult to do.
- Blindness - May result from bilateral sickle retinopathy.
- Problems of iron overload - Related to regular transfusion treatment.
