Sickle cell disease: diagnosis and health maintenance: Case

This boy has HbSS sickle cell disease, well managed on penicillin, hydroxyurea, and full immunisation, and the new finding is the abnormal transcranial Doppler. The right middle cerebral artery time-averaged mean velocity of 205 cm per second crosses the 200 cm per second threshold that defines the abnormal result, and this is a pre-stroke state that demands action. The annual trend, up from 175 cm per second last year, confirms that this is a new and real change rather than a measurement artefact. [3]

Interpretation of the findings

The key findings are the abnormal transcranial Doppler, the steady-state chronic haemolysis, and the good hydroxyurea response. The time-averaged mean velocity of 205 cm per second is abnormal, because the threshold is 200 cm per second or more, and the STOP trial showed that such a child has a high risk of a first stroke without treatment. The haemoglobin of 78 g per litre and the reticulocyte count of 12 percent are the expected steady state of HbSS, the chronic haemolysis, and the fetal haemoglobin of 18 percent shows a good response to the hydroxyurea, which is why his disease has been well controlled to this point. [8]

The penicillin and the immunisation are appropriately maintained, and there is no sign yet of organ injury. The question is not whether he is sick today, because he is not, but whether the abnormal Doppler is allowed to progress to a stroke, which it will in a substantial minority of untreated children. The interpretation is therefore that the boy has moved from a screened, low-risk child to one who needs a chronic transfusion programme to prevent a stroke. [3]

Management: the transfusion decision

The immediate management is the commencement of a chronic transfusion programme. The aim is to keep the haemoglobin S under 30 percent and the haemoglobin around 90 to 100 g per litre, given by simple or exchange transfusion every three to four weeks, and the STOP trial showed that this reduced the risk of a first stroke by about 90 percent. Before the first transfusion, the boy is phenotyped for the major red cell antigens to reduce the risk of alloimmunisation, which is common in the transfused child with sickle cell disease. [3][8]

The transfusion is not a lifetime commitment from the start, and the TWiTCH trial gives the exit strategy. Once the boy has been on the chronic transfusion for at least a year, with a normal current Doppler and no silent cerebral infarct on magnetic resonance imaging, he may be eligible to switch to optimised hydroxyurea, which the TWiTCH trial showed was non-inferior to continued transfusion. The phlebotomy that follows the switch reduces the iron load, so the transfusion becomes a bridge rather than a permanent state. [7]

Iron overload and its monitoring

The chronic transfusion brings the price of iron overload, and the fellow must monitor and treat it. Each unit of blood delivers about 200 mg of iron, and the body cannot excrete it, so the iron accumulates in the liver, the heart, and the endocrine glands. The ferritin and the liver iron content are monitored, and chelation is started when the ferritin exceeds 1000 micrograms per litre, with deferasirox as the usual first-line chelator in children. The aim is to prevent the cirrhosis, the cardiomyopathy, and the endocrine failure that untreated iron overload causes, and the TWiTCH switch is the best way to stop the iron accumulating. [8]

Counselling the family

The counselling addresses the change in the plan, the commitment, and the outlook. The family is told that the abnormal Doppler means the boy is at risk of a stroke, that the transfusion prevents it, and that the transfusion is given every three to four weeks and brings the need for iron monitoring. They are told that the transfusion may be temporary, because the TWiTCH switch to hydroxyurea is an option after a year if the Doppler stays normal and the magnetic resonance imaging shows no silent infarct. They are reassured that the hydroxyurea is working well, that the boy is otherwise healthy, and that with this package he remains on track for a stroke-free childhood and an adulthood in good health. [5][7]

The follow-up and the safety-net

The boy is reviewed in the sickle cell clinic every three to four weeks for the transfusion, the full blood count and the ferritin are checked before each visit, and the transcranial Doppler is repeated annually. The family is given a written emergency plan for fever, for pallor, and for any new neurological symptom, because a child on a transfusion programme who develops a headache, a weakness, or a seizure is a stroke until proven otherwise. The long-term plan is to keep him on the transfusion with chelation, to reassess for the TWiTCH switch at a year, and to plan the transition to the adult haemoglobinopathy service in good time. [5][8]