Sickle cell acute complications: SAQ

This boy has acute chest syndrome, the most feared complication of sickle cell disease and the leading cause of death, superimposed on a vaso-occlusive pain crisis. The diagnosis rests on the new pulmonary infiltrate on the chest radiograph together with the fever, the breathlessness, the cough, and the hypoxia, and the saturation of 89 percent on room air marks this as a moderate-to-severe episode that needs oxygen, antibiotics, analgesia, and preparation for transfusion at once. The fact that it emerged after admission for a pain crisis is typical, because the splinting from rib pain causes atelectasis that seeds the lung. [4]

Question 1 (10 marks)

Outline the diagnosis and the immediate and definitive management of this boy's acute chest syndrome, justifying each step with the relevant evidence. [4]

A full-mark answer addresses the diagnosis, the resuscitation, the antibiotics, the analgesia and the fluids, and the transfusion strategy by severity. [1]

Diagnosis and resuscitation (3 marks). The combination of a new pulmonary infiltrate with fever, breathlessness, cough, and hypoxia meets the definition of acute chest syndrome, and the saturation of 89 percent signals significant hypoxia. The immediate response is oxygen delivered to keep the saturation at or above 92 percent, and the intensive care team is informed early because the deterioration can be rapid. The airway, the breathing, and the circulation are assessed, and the child is monitored continuously for the respiratory rate, the saturation, and the work of breathing. [4][1]

Antibiotics (2 marks). Broad-spectrum antibiotics are started after the blood cultures, covering the common bacteria and the atypicals. A third-generation cephalosporin such as cefotaxime or ceftriaxone is combined with a macrolide such as azithromycin or erythromycin, because Mycoplasma and Chlamydia are among the infectious causes, and the fat embolism from the infarcted marrow is the other principal mechanism. [4]

Analgesia, fluids, and supportive care (2 marks). The underlying pain crisis is treated with intravenous morphine at 0.1 mg per kg, with reassessment and repeat doses, because the relief of the rib pain allows the child to breathe deeply and to use the incentive spirometry that prevents the atelectasis. The fluids are isotonic and given at maintenance, because over-hydration precipitates pulmonary oedema and worsens the chest. Incentive spirometry every two hours while awake is prescribed. [1]

Transfusion strategy (3 marks). The transfusion is guided by the severity and the haemoglobin trend. A simple transfusion is given when the haemoglobin falls below the baseline or the oxygen requirement rises, and it is kept cautious, never pushing the haemoglobin above about 100 g per litre, because the higher haematocrit causes hyperviscosity and worsens the sickling. For the moderate-to-severe episode with worsening hypoxia or multilobar infiltrates, the exchange transfusion is the standard, and it brings the haemoglobin S under 30 percent, the same target used after a stroke. The exchange transfusion removes the sickled blood and replaces it with donor blood, and it is the modality that reverses the severe acute chest. [7][4]

Question 2 (10 marks)

Explain how hydroxyurea and chronic transfusion change the trajectory of acute sickle complications, and critically appraise the trial and the study evidence. [5]

A full-mark answer reproduces the mechanism, appraises the studies, and links the acute management to the prevention. [1]

Hydroxyurea (4 marks). Hydroxyurea raises the fetal haemoglobin, which dilutes the haemoglobin S and blocks its polymerisation, and it lowers the white cell count, which reduces the inflammation of vaso-occlusion. The Multicenter Study of Hydroxyurea, published by Charache and colleagues in 1995, showed that the drug reduced the frequency of the painful crises, the acute chest syndrome, and the transfusion requirement, and the benefit extends to children. The current recommendation is to offer hydroxyurea to every child with HbSS from nine months, at a starting dose of 20 mg per kg per day escalated to the maximum tolerated dose, and a child with frequent crises or recurrent acute chest syndrome is a prime candidate for an optimised regimen. [5]

The Vichinsky study and the acute chest (3 marks). The Vichinsky study of the Cooperative Study of Sickle Cell Disease, published in the New England Journal of Medicine in 2000, defined the causes and the outcomes of the acute chest syndrome and showed that the infection and the fat embolism from the marrow infarction were the principal mechanisms, and that the acute chest syndrome was a leading cause of death. The study established the framework for the oxygen, the antibiotics, and the transfusion that form the modern management, and it set the case for the prevention through hydroxyurea and incentive spirometry. [4]

Chronic transfusion and prevention (3 marks). The child who has had a severe or a recurrent acute chest syndrome, and the child who has had an acute stroke or an abnormal transcranial Doppler, is placed on a chronic transfusion programme that keeps the haemoglobin S under 30 percent, given every three to four weeks. The STOP trial showed that this strategy prevented the first stroke in the child with an abnormal Doppler, and the same principle of reducing the haemoglobin S underpins the treatment of the severe acute chest and the acute stroke. The chronic transfusion brings the iron overload that needs the chelation with deferasirox, and the prevention package of newborn screening, penicillin, immunisation, hydroxyurea, and transfusion is what has driven the modern survival. [7][1]