The Molecular Pathology of Non-Malignant Haematological Disease

In almost all aspects of biomedical science, molecular pathology has brought unprecedented value in the diagnosis and management of human disease. Numerous commentators cite haematological disease as the leading genetic cause of global mortality and morbidity, and of these, those of the red blood cells are the most frequent. This narrative review, with a historical perspective, will discuss the role of genetics in these conditions, the leading pathology of red blood cells being the haemoglobinopathies, principally sickle cell disease and thalassaemia, with their many variants, and with potential roles for non-coding RNAs. The impact of genetics into conditions of the red cell cytoplasm will consider the enzymopathies, led by glucose-6-phosphate dehydrogenase deficiency, and extend to those of the cell membrane, causing disease such as hereditary elliptocytosis. Mutations in genes coding almost all the coagulation factors, and several platelet abnormalities, are discussed, as are those linked to conditions of iron overload. Previous, current and evolving technologies for diagnostic testing and their link with potential targeted therapeutic options for patient management are considered.