Symptomatic treatment

The symptomatic management of severe P-thalassaemia involves regular blood transfusion, the judicious use of splenec-tomy if hypersplenism develops, and the administration of chelating agents to attempt to deal with the problem of iron overload from regular blood transfusion. When the diagnosis of severe P-thalassaemia is suspected during the first year of life, the infant should be followed for several weeks to make sure that the haemoglobin is falling to a level at which regular transfusion will be necessary, particularly important if he or she has presented with infection that may cause the haemoglobin level to fall. It is difficult to be dogmatic about exactly when transfusions should be started, but if the infant is severely anaemic and is feeding poorly or otherwise failing to thrive, transfusion will almost certainly be necessary. The object is to maintain the pre-transfusion haemoglobin level above 9 g/dL, and this usually requires transfusion every 4 weeks. Either washed or frozen red cells should be used, but whole blood should be avoided because of the danger of sensitization to serum or white cell components. A full blood group genotype should be obtained before the first transfusion. A careful check on the pre- and post-transfusion haemoglobin level should be kept and the transfusion requirements carefully plotted. It is vital that body iron status is assessed regularly in these children. Although this may be achieved in part by serum ferritin estimations, there is good evidence that this does not provide a completely accurate reflection of body iron, which is much better assessed by measuring the hepatic iron concentration. Whenever possible, these children should undergo regular liver biopsies, ideally annually but at least every 2-3 years; in experienced hands, this has a very low morbidity and provides a much better guide to the effectiveness of iron chelation therapy. Non-invasive approaches to assessing body iron load are discussed in Chapter 4.

The gold standard for iron chelation therapy is desferriox-amine. There is extensive evidence that if this drug is given at adequate doses, and if compliance is satisfactory, patients may be maintained indefinitely at safe body iron loads and may grow and develop normally. At present, it is recommended that the drug is started at a dose of 25-35 mg/kg, given by an 8- to 12-h subcutaneous infusion overnight, approximately 1 year after the start of regular transfusion. The usual dose in older children and adults is 40 mg/kg. Patients should receive up to 200 mg of ascorbate on the day of infusion, approximately 30 min before it is started. Intolerance to desferrioxamine is extremely rare but, particularly at high doses, there may be ocular changes, including cataracts and retinal damage, or acoustic nerve impairment. Other complications, particularly if the drug is given to patients with low body iron levels, include reduction in linear growth, sometimes associated with evidence of cartilaginous dysplasia of the long bones and spine. Infection with Yersinia enterocolitica is a rare but well-documented complication. But these complications are rare in children who are kept under careful surveillance and the main problem posed by desferrioxamine is non-compliance; much can be done by intensive support by doctors, dedicated nursing staff and families. However, for this reason the search continues for an effective oral chelating agent. The place of these agents at present for the prevention and management of iron overload is discussed in Chapter 4.

If there is a marked increase in blood requirement, hyper-splenism should be suspected. Any thalassaemic child with an easily palpable spleen probably has some degree of hypersplen-ism. Splenectomy should be carried out as late as is feasible and, if possible, not in the first 5 years because the incidence of post-splenectomy infection seems to be particularly high in early childhood. Apart from increased transfusion requirements, the presence of neutropenia or thrombocytopenia is a useful guide to the presence of hypersplenism. Pneumococcal vaccine should be administered before surgery, and after the operation children should be maintained on prophylactic penicillin indefinitely and the parents warned about the danger of overwhelming infection. Because of this risk it is becoming customary to also immunize these children against Streptococcus pneumoniae and Haemophilus influenzae.

Well-transfused children maintained on a good diet do not usually develop important vitamin deficiency states. However, folic acid deficiency occurs in poorly transfused children or in those with thalassaemia intermedia, and it is probably better to maintain these patients on regular folate supplements. In those who develop iron loading with end-organ failure, endocrine replacement therapy may be necessary to improve growth and secondary sexual development and, if necessary, to treat diabetes mellitus. These children require expert endocrinological assessment before treatment. Because the occurrence of osteoporosis is also likely to be due to hypogonadism, similar precautions should be followed. In those who develop cardiac abnormalities, intensive chelation therapy may improve cardiac function.

However well children are managed there is a serious risk of blood-borne infection, particularly hepatitis B and C, HIV and, in tropical countries, malaria. Much can be achieved by adequate screening of blood products, but the possibility of these complications should be constantly borne in mind and viral infec tions treated with appropriate antiviral agents. In some tropical countries, particularly where screening of the blood is difficult, prophylactic antimalarial therapy is given after transfusion.

The role at present for more experimental forms of therapy, notably attempts to reactivate higher levels of fetal haemoglobin production, which, except in a few rare cases, have not been successful for the treatment of thalassaemia, is discussed in Chapter 7, and the current status of research into somatic gene therapy is reviewed in Chapter 26.

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