The inherited haemoglobin disorders are the commonest diseases attributable to single defective genes. They fall into two main groups: the structural haemoglobin variants including sickle cell disease (SCD) and the thalassaemias, which are caused by defective globin production. Carrier numbers of >270 million and more than three hundred thousand children born each year with one of the thalassaemia syndromes or one of the structural haemoglobin variants have been estimated (WHO 1989, 1994,2008). The extremely high frequency of the haemoglobin disorders compared with other monogenic diseases reflects natural selection mediated by the relative resistance of carriers against P. falciparum malaria. Other factors that may be involved include the widespread practice of consanguineous marriage, increased maternal age in the poorer countries, and gene drift and founder effects. For these reasons the thalassaemias are most frequent in Southeastern and Southern Asia, in the Middle East, in Mediterranean countries and in North and Central Africa. However, as the result of mass migrations of populations from high prevalence areas, thalassaemias are now encountered in most countries.

Such countries include the USA, Canada, Australia, South America, the United Kingdom and France, where migration occurred up to a century ago and where large ethnic minority groups are now entering their fourth and even fifth generation.

More recent migration movements from highly endemic countries have been to Northern and Western Europe, where the prevalence of haemoglobin disorders in the indigenous population was very low, including Germany, Belgium, the Netherlands and, more recently, Scandinavia (Kattamis A, Forni GL, Aydinok Y, Viprakasit V. Changing Patterns in the Epidemiology of beta-Thalassemia. Eur J Haematol 2020).These changes have challenged health professionals and policy-makers throughout the region in providing equitable access to quality services for the prevention and treatment of haemoglobin disorders. The epidemiological data available mainly in endemic countries underestimate the future health burden resulting from inherited haemoglobin disorders; effectively addressing the control of these disorders in these countries requires considerable work, financial backing and certainly political commitment. The main difficulty is that the populations of these countries are not homogeneous, as was the case in the Mediterranean countries where the earliest control programmes were successfully established. Programmes to reduce the number of seriously affected individuals follow two approaches: 1. population screening and counselling programmes established to educate populations about the risks of having affected children; 2. population screening or screening in prenatal clinics where if a women is a carrier the partner is screened and if positive, following counselling they are offered a prenatal diagnosis and termination of affected fetuses. Prenatal diagnosis programmes well established in the Mediterranean region resulting in a major reduction in newborns with severe forms of thalassaemia. Such programmes are now available in other countries including China, India, Iran, Lebanon, Pakistan, Singapore and Thailand and several other countries are establishing similar programmes. Whatever the results of the screening programmes, they require a proper education of the population about the nature of inherited haemoglobin disorders. This education requires input from many sectors of society, including the media, public health workers, local volunteer societies and the medical community (Weatherall DJ: Disease control priority in developing countries).

Beside prevention, a main objective is to offer to subjects affected by haemoglobin disorders the most efficacious treatment. Studies evaluating thalassaemia major cohorts in both developed and developing countries continue to show a progressive improvement in life expectancy. For this reason there is an urgent need to bridge a wide gap until every patient in every part of the world has equal access to quality medical care. An essential means of doing so is through global collaboration on haemoglobin disorders, enabling all countries to benefit from each other’s experience. Health authorities need to recognise haemoglobin disorders as a significant threat to public health − one that deserves the development and implementation of national policies for treatment and prevention.

The instruments required to support such policies include:

• Standardised guidelines for laboratory services
• National guidelines for the management of thalassaemia
• Epidemiological information and surveillance
• Establishment of an educational programme for health professionals, patients, parents and the community

The full costs of treating patients with inherited disorders of haemoglobin is extremely variable among countries depending on different health care systems, varying methods of obtaining blood, different practices in screening for blood pathogens and different costs of drugs and equipment. It is evident that all countries would benefit from the sharing of experience and expertise in order to harmonise and optimise the quality of treatment as much as possible. The need for management guidelines for transfusion-dependent thalassaemias (TDT) is clear. During the past four years, six major TDT management guidelines have become available for use by thalassaemia care givers (TIF, US, Canadian, UK, Italian and Australian Guidelines). A comparison among those guidelines has been recently published (Musallam KM et al. Acta Haematologica 2013). In the light of swiftly evolving evidence, the need for revisiting and updating TDT management recommendations remains crucial. More importantly, ensuring access to such guidelines and careful application and implementation should only help arriving at early diagnosis of morbidity to allow prompt and effective management. It would also allow early prediction of risk and would enable preventive measures to be set in place saving unnecessary health care costs. Moreover in view of novel therapies that are under development or already approved such as gene therapy and molecules targeting ineffective erythropoiesis (Luspatercept) it is mandatory to guarantee to thalassaemia patients all over the world an optimal standard of care in order to face in good clinical status the future scenario of thalassaemia cure

This updated fourth edition of the TIF guidelines will offer valuable information to all allied healthcare professionals involved in the treatment of patients with TDT. It includes updated information on new approaches for more effective, safe and less laborious treatment, and an overview of the progress achieved to date towards a total cure using methods such as gene therapy and stem cell transplantation.