Erythropathology and hematopoiesis failure - Causes and diagnosis of rare anemias

Lead researchers: Dr. Joan Lluís Vives Corrons and Dr. Maria del Mar Mañú

Rare anemias

Anemia is not, properly speaking, a disease, but rather a clinical manifestation of a disease that might have a number of causes. All those diseases in which the main clinical manifestation is anemia, and which affect fewer than 5 of every 10,000 people, are considered rare anemias. This group of anemias, mainly congenital or hereditary in origin, comprises some 90 different diseases, mainly serious ones and often difficult to diagnose. Because of this, little is known about them and they deserve special attention.

Anemias, in general, conform to two fundamental mechanisms:

  • Hematopoiesis failure, as a consequence of which the bone marrow ceases to function well due to a deficiency such as, for example, Fanconi's anemia or a deregulation such as, dyserythropoietic anemia.
  • Defect or lesion of the red blood cells leading to their destruction before time (hemolytic anemia). There can be many different causes, amongst the most prominent of which are those with a congenital or hereditary origin such as, for example, hemoglobinopathies (sickle-cell anemias, Cooley's anemia), enzymopathies (favism, Pyruvate kinase deficit) or membranopathy (hereditary spherocytosis). Notable amongst the acquired forms are autoimmune hemolytic anemia, mechanical hemolytic anemia and paroxysmal nocturnal hemoglobinuria (PNH).

The challenge of building networks

The rare, or very infrequent, character of these anemias means that work must be conducted through international networks, without which it is very difficult to provide patients with a correct clinical health care, or make fruitful investigations that add to our knowledge of them. With this in mind, Dr. Joan Lluís Vives Corrons and his team cofounded the European Network for Rare and Congenital Anaemias (ENERCA), a European project that has been co-financed by the European Commission since 2002 ( Over the last three years this project has developed four platforms to design, validate and implement new digital services (e-ENERCA) aimed at improving the volume and flow of information for the diagnosis of these minority anemias (Telemedicine), the patient registry (e-Registry), continuing professional training (e-Learning) and, above all, the search for epidemiological, physiopathological and molecular mechanisms.

Thanks to the implementation of the European Directive on Transfrontier Health (EC 2011) in 2016 by Dr. Vives and Dr. Pierre Fenaux of the Saint Louis Hospital in Paris, it has been possible to widen the European network, which in principle had been limited to anemias, to include other malignant and non-malignant blood diseases by means of the creation of a European Reference Network for Rare Blood Diseases, known as EuroBloodNet. This has enabled a European map to be drawn up of leading centres for, and experts on, blood diseases with their corresponding contacts, essential for the sharing of knowledge and refining diagnosis.

Why do we need to investigate?

80% of rare anemias are congenital and are consequently diagnosed during the first years of life, that is to say, during childbirth (neonatal anemias) or during infancy. They are considered infant, or childhood diseases. They are usually serious diseases, and sometimes difficult to diagnose, and this almost always means that they cause great distress to families They are called rare because, in Europe, they affect fewer than 5 of every 10,000 people. This means that there is a large range of possibilities in the field of research, both with regard to the diagnosis of those with complex mechanisms as well as with regard to treatment. There being no treatment for most of them, such treatment as exists is based on palliative procedures, with the exception of the transplant of hematopoietic progenitors.

The impact of our work

The team's current projects focus on the different aspects concerning red blood cells, their function and the epidemiological impact rare anemias currently have. The following are the various lines of research taking place:

- A study of the functional behaviour of red blood cells, as cells circulating in the blood flow, through an analysis of their composition, shape, and capacity for deformation in different media that emulate the characteristics of microcirculation. This makes it possible to know the degree of erythrocyte lesion and the capacity of red blood cells to overcome the barriers imposed by circulation through different tissues, especially the spleen.

- A study of the molecular base of rare anemias with the use of gene panels, which enable the identification of the mutations involved in each of them. These mutations modify the clinical manifestation of the anemias, and may, in some way, explain their etiological or physiopathological mechanisms.

- A number of studies focused on certain aspects of erythrocytic pathology such as, for example, the PKDeep project, centred on the study of the pyruvate kinase enzyme (PK), by means of the creation of a platform which includes diagnostic, epidemiological, molecular, and therapeutic aspects. The PK enzyme is vital for red blood cell energy maintenance and PK deficiency (PKD) and is one of the most frequent causes of congenital nonspherocytic hemolytic anemia (CNSHA). With an estimated incidence of one in 20,000 people, one of the main aims of this project is to establish a European registry of cases of PK enzyme deficiency.

- A study of the multi-factor mechanism of anemia in persons of advanced age. The aim of the study is to examine how the ageing of the bone marrow can lead, not only to a breakdown in the production of red blood cells, but also to a malignant transformation of pluripotent stem cells. This is an area which has not yet been well studied and about which little is consequently known.

- To continue maintaining and establishing new links with leading European rare disease networks, especially with EuroBloodNet, in order to make progress in the diagnosis of rare hematological diseases (RHD), to improve our understanding of them and to facilitate transfrontier and multidisciplinary team research.

Josep Carreras Leukaemia Research Institute Dossier

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For more information, the following web pages can be consulted:

Enerca - Anaemias



Webpage updated 11/13/2018 17:31:12