Sickle cell anaemia is a genetic condition that causes sickle (crescent) shaped red blood cells. This makes the red blood cells fragile and more easily destroyed, leading to a haemolytic anaemia. Patients with sickle cell anaemia are prone to various types of sickle cell crises.
Haemoglobin is the protein in red blood cells that transports oxygen.
During the development of a fetus, from 32 to 36 weeks gestation, the production of fetal haemoglobin (HbF) decreases. At the same time, adult haemoglobin (HbA) is produced in greater quantities. Over time there is a gradual transition from HbF to HbA. At birth, around half the haemoglobin produced is HbF and half is HbA. By 6 months of age, very little fetal haemoglobin is produced. Eventually, red blood cells contain almost entirely HbA.
Patients with sickle-cell disease have an abnormal variant called haemoglobin S (HbS). HbS causes red blood cells to be an abnormal “sickle” shape.
Sickle cell anaemia is an autosomal recessive condition where there is an abnormal gene for beta-globin on chromosome 11. One copy of the gene results in sickle-cell trait. Patients with sickle-cell trait are usually asymptomatic. Two abnormal copies are required for sickle-cell disease.
Relation to Malaria
Sickle cell disease is more common in patients from areas traditionally affected by malaria, such as Africa, India, the Middle East and the Caribbean. Having one copy of the gene (sickle-cell trait) reduces the severity of malaria. As a result, patients with sickle-cell trait are more likely to survive malaria and pass on their genes. Therefore, there is a selective advantage to having the sickle cell gene in areas of malaria.
Pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy. Sickle cell disease is also tested for on the newborn screening heel prick test at 5 days of age.
- Increased risk of infection
- Avascular necrosis in large joints such as the hip
- Pulmonary hypertension
- Painful and persistent penile erection (priapism)
- Chronic kidney disease
- Sickle cell crises
- Acute chest syndrome
- Avoid dehydration and other triggers of crises
- Ensure vaccines are up to date
- Antibiotic prophylaxis to protect against infection, usually with penicillin V (phenoxymethypenicillin)
- Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
- Blood transfusion for severe anaemia
- Bone marrow transplant can be curative
Sickle Cell Crisis
Sickle cell crisis is an umbrella term for a spectrum of acute crises related to the condition. These range from mild to life threatening. They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.
There is no specific treatment for sickle cell crises and they are managed supportively:
- Have a low threshold for admission to hospital
- Treat any infection
- Keep warm
- Keep well hydrated (IV fluids may be required)
- Simple analgesia such as paracetamol and ibuprofen (NSAIDs should be avoided where there is renal impairment)
- Penile aspiration is used to treat priapism
Vaso-occlusive Crisis (AKA painful crisis)
Vaso-occlusive crisis is caused by the sickle shaped blood cells clogging capillaries and causing distal ischaemia. It is associated with dehydration and raised haematocrit. Symptoms are typically pain, fever and those of the triggering infection. It can cause priapism in men by trapping blood in the penis, causing a painful and persistent erection. This is a urological emergency and is treated with aspiration of blood from the penis.
Splenic Sequestration Crisis
Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to severe anaemia and circulatory collapse (hypovolaemic shock).
Splenic sequestration crisis is considered an emergency. Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock.
Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises. Recurrent crises can lead to splenic infarction, resulting in susceptibility to infections.
Aplastic crisis describes a situation where there is temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19.
It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.
Acute Chest Syndrome
A diagnosis of acute chest syndrome requires:
- Fever or respiratory symptoms, with:
- New infiltrates seen on a chest xray
Acute chest syndrome can be due to infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).
Acute chest syndrome is a medical emergency with a high mortality. It requires prompt supportive management and treatment of the underlying cause:
- Antibiotics or antivirals for infections
- Blood transfusions for anaemia
- Incentive spirometry using a machine that encourages effective and deep breathing
- Artificial ventilation with NIV or intubation may be required
Last updated January 2020