Rare Analytical Need
Anemia becomes much more serious in countries where rare hereditary forms can remain undiagnosed. A symposium aims to tackle the issue head on – and analytical science has its part to play.
Anemia, defined as a decrease of hemoglobin (Hb) concentration in blood, is a common condition in humans. It has a wide variety of causes, both congenital and acquired, but it is always a manifestation of an underlying disease, not a disease in itself. Iron deficiency (in women and children) and chronic diseases (in adults and the elderly), are the most frequent causes of mild to moderate anemia in developed countries. Diagnosis of decreased Hb levels is relatively easy and inexpensive; all modern automated and semi-automated analyzers measure Hb concentration with great precision and accuracy.
However, another group of anemia sufferers occurs at a frequency of less than one in 2,000 in Europe. Up to 80 percent of these rare anemias (RA) are hereditary. Due to the low number of patients, a lack of professional experience, and social or cultural barriers, a large percentage of RAs remain undiagnosed. The clear need to mobilize resources will only be achieved through coordinated multi-centre and multi-disciplinary action. The European Commission (EC) is, therefore, co-financing the European Network for Rare and Congenital Anaemias (ENERCA). One activity is the 5th European Symposium on Rare Anaemias*, a forum on diagnosis and clinical management of RA, and a workshop to explore the types of tests that could provide correct diagnosis most quickly.
For RAs, the pivotal diagnostic tests are red blood cell (RBC) morphology examination and reticulocyte count. The latter allows differentiation between a central (bone marrow) or peripheral (hemolytic) origin of the anemia. Peripheral blood film examination and osmotic fragility tests (OFT) can sometimes confirm the diagnosis of hereditary spherocytosis, one of the inherent causes of rare anemias. When the OFT is negative, RBC enzyme assays are required for the diagnosis of a hereditary enzymopathy, with glucose-6-phosphate dehydrogenase (G6PD) or pyruvate kinase (PK) being the most common.
Hemoglobinopathies, which lead to moderate or severe anemia, are the most common genetic defects worldwide, with an estimated number of 269 million carriers. These hereditary conditions are the consequence of mutations that result in abnormal hemoglobin. Thalassaemias, on the other hand, result from decreased synthesis of normal globin chains. The two conditions can overlap. In Europe, certain populations of southern countries are particularly at risk of thalassaemia – the cause of so-called ‘Mediterranean Anemia’. But increasing migration to Europe from African and Asian countries has drastically changed this scenario: sickle-cell disease (SCD) is becoming an important challenge for public health care. Diagnostic approaches for these disorders range from electrophoresis and high performance liquid chromatography (HPLC) for hemoglobin fractionation in beta thalassemia and structural haemoglobinopathies (sickle cell anaemia) to polymerase chain reaction (PCR) for alpha thalassemia and gene sequencing for the identification of specific mutations.
The two key discussion points at the symposium of greatest relevance for those in the analytical sciences are (a) preventive programs for SCD control, such as neonatal screening, and (b) new methodologies for diagnosis and genetic counseling, and genetic characterization in cases where laboratory ‘blind spots’ are caused by co-inheritance of hemoglobinopathies and other RBC genetic defects. The organizers would welcome your input!
*The 5th European Symposium on Rare Anaemias takes place 15–16 November, 2013, in Ferrara Italy. For more information, visit: www.enerca.org
The professor of medicine and head of the haematology laboratory department of the Hospital Clinic i Provincial (University of Barcelona) since 1976, Joan LLuis-Vives Corrons has been influential in haematology research, education and diagnosis. “My main focus has been on the development of new procedures for the diagnosis of anaemias and haematological malignancies (acute and chronic leukaemias and lymphomas) as well as in the standardization and quality assessment of haematology laboratory practice”.
