You are the intern in the emergency department; Ambrose Okeke who is 25 years old is visiting from South Africa. He presents with severe pain in his left leg which has not been relieved by panadeine forte. Ambrose has sickle cell disease and many episodes of similar pain which occasionally require analgesia with narcotics.
You observe that he is in obvious pain and note that his temperature is elevated at 37.8°C.
Symptoms in sickle cell disease vary from a mild asymptomatic disorder to a severe haemolytic anaemia and recurrent severe painful crises. The condition may present in childhood with anaemia and mild jaundice. In the older patient, vaso-occlusive problems occur owing to the sickling in the small vessels of any organ, mimicking many medical and surgical emergencies. Typical infarctive sickle crises include:
Haemolytic anaemias are caused by increased destruction of red cells. The red cell normal survives about 120 days, but in haemolytic anaemias the red cell survival times are considerably shortened. There is no definite explanation why red cells are removed from the circulation at the end of their life span. Breakdown of normal red cells occurs in the macrophages of the bone marrow, liver and spleen.
Consequence of haemolysis.
Shortening of red cell survival does not always cause anaemia as there is a compensatory increase in red cell production by the bone marrow. If the red cell loss can be contained within the marrow's capacity for increased output, then a haemolytic state can exist without anaemia. The bone marrow can increase its output by six to eight times. In addition, immature red cells are released prematurely.
Some intravascular haemolysis may occur in sickle cell disease owing to increased mechanical fragility of the severely damaged cells. The average red cell survival correlates with the percentage of irreversibly sickled cells in circulation and is shortened to approximately 20 days.
When red cells are rapidly destroyed within the circulation, haemoglobin is liberated. This is initially bound to plasma haptoglobins but these soon become saturated. Excess free plasma Hb is filtered by the renal glomerulus and enters the urine, although small amounts are reabsorbed the renal tubules. In the renal tubular cell, Hb is broken down and becomes deposited in the cells as haemosiderin. The liver plays an important role in removing HB bound to haptoglobin and haemopexin and any remaining free Hb.
Diagnosis of sickle cell anaemia is on the basis of:
The most important structural abnormality of the Hb chain is sickle cell haemoglobin (Hb S). Hb S results from a single – base mutation of adenine to thymine which produces a substitution of valine for glutamine at the sixth codon of the b globin chain. In the homozygous state (sickle cell anaemia) both genes are abnormal Hb SS, where as in the heterozygous state (sickle cell trait) only one chromosome carries the gene. As the synthesis of Hb F is normal, the disease usually does not manifest itself until the Hb F decreases to adult levels at about 6 months of age.
Clinical presentation depends on whether the onset of haemolysis is gradual or abrupt and on the severity of erythrocyte destruction. A patient with mild haemolysis may be asymptomatic. In more serious cases, the anaemia can be life threatening, and patients can present with angina and cardiopulmonary decompensation. The clinical presentation also reflects the underlying cause for haemolysis.
Painful sickle cell crises are acute exacerbations of sickle cell disease characterised by severe generalised bone pain due to infarction of the marrow. Almost any bone may be involved and there is a tendency for the infarcts to become infected. Sometimes infection may occur with unusual organisms such as Salmonella.
Treatment is required when crises occur for the control of pain, the maintenance of hydration, correction of anaemia and prevention and treatment of infection.
Long term problems include: