Fetal haemoglobin in homozygous sickle cell disease

Synthesis of fetal haemoglobin is prolonged in homozygous sickle cell disease. Its intracellular distribution is irregular and red cells containing high levels of Hb F enjoy greater protection from sickling and subsequent destruction. This relationship is reflected in a number of associations between Hb F level and the haematological and clinical parameters of the disease. High fetal haemoglobin levels are associated with more normal red cell survival, more normal oxygen affinity, and more normal red cell characteristics whereas clinically they are associated with less evidence of vessel obstruction, persistence of splenomegaly, more normal skeletal development and body habitus, and a generally more benign clinical course. Attempts to prolong Hb F synthesis might therefore be expected to lead to amelioration of the clinical features of the disease. The factors leading to persistence of Hb F synthesis is SS disease are largely unknown although they appear to be operative as early as the first three months of life.