LAUSR

For a small proportion of the UK population, life can only be sustained through regular transfusions of blood. Such is the reality for the ~600 people living with thalassaemia major and ~200–300 living with conditions such as Diamond– Blackfan anaemia (DBA), congenital dyserythropoietic anaemia (CDA), congenital sideroblastic anaemia (CSA) and other rare inherited anaemias. For this small group of individuals, transfusions alone extend survival from the first weeks or months after birth, to approximately the first or second decades. Without further intervention, death inevitably follows at the hands of heart failure and liver cirrhosis, direct complications of iron, derived from the transfused erythrocytes, accumulating in the tissues. Having evolved as a species that can only regulate iron by choosing to absorb it or not, receiving iron parenterally poses a problem that our physiology cannot solve. Toxic iron overload is addressed by pharmacological intervention instead, one which takes the shape of ‘lobster-like claws’, the iron chelators. Between these molecular claws lies the iron, snatched from their natural iron-carrying proteins or directly from tissues, to then be excreted via the urine, faeces or both. The first chelator to be used in clinical practice was desferrioxamine. Initially given through the intramuscular route — a painful and disfiguring necessity endured by an early cohort of stoical thalassaemia patients — the development of a subcutaneous formulation revolutionised the quality of life and outcomes for patients with transfusiondependent thalassaemia (TDT). While the search for the perfect oral chelator has not yet yielded a replacement with perfect pharmacokinetics and devoid of side effects, both deferiprone and deferasirox are widely available and, if used consistently by patients, should prevent any iron from accumulating in the tissues. Would that this should suffice. However, the complexities of caring for patients with transfusion-dependent anaemias result from a mixture of biological reasons and human factors. The guidelines from Shah et al., on the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias, for the first time summarise our current understanding of the available evidence on chelation as best applied to each type of anaemia. These guidelines represent a resource likely to benefit far more than UK patients, but also those all over the world whose clinicians will welcome the clear advice.