Sickle cell anaemia is the most common haemoglobinopathy worldwide and particularly affects the African-Caribbean population.
In sickle cell anaemia, abnormal haemoglobin is formed following a beta chain substitution at nucleic acid level. This HbS forms liquid crystals in the deoxygenated state and the resultant red cell loses its characteristic flexible biconcave disc shape becoming a rigid sickle.
Sickle cell anaemia is inherited in an autosomal recessive manner; homozygosity for the abnormal beta chain results in disease. The heterozygous or carrier state is termed sickle cell trait and only some of the red blood cells are affected. Clinically this is well tolerated with, normally, no complications.
The heterozygous trait confers some protection from falciparum malaria and this probably accounts for the higher incidence in those of African-Caribbean descent.
Diagnosis
Newborn screening for sickle cell disease is becoming increasingly common in those thought to be at high risk.
FBC may show a reticulocytosis and anistocytosis alongside anaemia usually in the range 60-100g/l. This anaemia is often well tolerated as HbS releases oxygen more readily than normal HbA. If suspicious, blood film and haemoglobin electrophoresis are confirmatory tests.
Vaso-occlusion
The hallmark of sickle cell disease is episodic severe painful vaso-occlusion. Rigid sickle cells are prone to becoming lodged in the microcirculation. The chance of this occurring is increased in various situations including dehydration, cold temperatures, exhaustion, infection, emotional stress and menstruation.
One or more anatomical sites may be targeted, most commonly the hands (dactylitis), the hips, the shoulders and the vertebrae. These attacks can be self-limiting, although infarction of bone is a risk and avascular necrosis of the femoral head can be a crippling complication.
Complications
Splenic function is to remove abnormal erythrocytes from the circulation. A heavy load of abnormal red blood cells often leads to splenomegaly, which may be massive and can occur early in life.
The enlarged spleen has a tendency to pool erythrocytes and platelets. When this sequestration occurs acutely a significant fraction of red blood cells and platelets may be temporarily removed from the circulation, resulting in severe and sudden profound anaemia accompanied by a painful splenomegaly and a risk of hypovolaemic shock.
This is termed a sequestration crisis.
In later years, the rigid sickle cells usually cause infarction of the splenic microcirculation and the spleen involutes, effectively undergoing autosplenectomy.
Risk of infection, especially from encapsulated organisms is high and prophylactic daily penicillin and annual vaccination for influenza and pneumococcus are particularly important.
Alongside infection risk from functional asplenism, patients with sickle cell disease tend to be immunocompromised.
Pneumonia, osteomyelitis and septic arthritis are particular risks and can pose diagnostic difficulty, mimicking symptoms of vaso-occlusive crisis. Parvovirus infection may trigger a potentially fatal aplastic crisis.
Renal papillary necrosis often occurs in childhood resulting in haematuria and a reduced ability to concentrate urine, increasing the risk of dehydration and sickle crisis.
Historically untreated priapism and resulting impotence has been a major source of morbidity. Stuttering priapism often precedes a major event and may be terminated with fluids, analgesia, urination and bathing.
Acute chest syndrome is a leading cause of death in sickle cell disease. Vaso-occlusion results in chest wall pain causing poor expansion, hypoventilation and atelectasis. Hypoxia results, compounding infection and a predisposation to marrow fat embolisation. Hospital management is required.
Profound and potentially fatal haemorrhagic stroke may be heralded by thunderclap headache, which should prompt urgent neurological assessment. Ischaemic event frequency is also markedly increased.
Pigmented gallstones occur frequently and are often a presenting feature in adults not diagnosed at birth.
Management
Patient education is vital and support groups and experienced centre access should be available. Key considerations include maintaining adequate hydration status, keeping warm and avoiding physical and, where possible, emotional pain. Infection should be treated aggressively.
Vaso-occlusive crises require prompt treatment with rest, analgesia and oral rehydration. Clinicians should have a low threshold for hospital admission for IV rehydration, analgesia and antibiotic administration as required.
Opiate use is commonplace. Blood transfusion is often considered when severe anaemia accompanies an acute crisis and exchange transfusion may benefit patients suffering unusually painful crises. Some patients are treated with hydroxyurea under specialist care.
- Dr Cumisky is a locum GP in Bath
Management of crises
- Rehydration
- Analgesia
- Rest
- Consider antibiotics
- Low threshold for admission
