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6.1 Antibody-mediated haemolytic anaemia includes autoimmune and alloimmune haemolytic anaemia. There may also be antibodies to drugs present on the surface of the red cell which can also cause haemolysis.
6.2 Non-antibody factors external to the red cell that cause haemolytic anaemia include mechanical factors, inflammation, and infections, such as by the parasite that causes malaria.
6.3 The two major types of haemoglobinopathy are sickle cell disease and thalassaemia. The molecular basis of the former is qualitative—a very small difference in an otherwise largely normal molecule of haemoglobin. In thalassaemia, the abnormality is quantitative—a large proportion of the entire globin molecule is often missing.
6.4 The basis of the molecular determinants of the qualitative beta globin haemoglobinopathies are of different mutations in the beta globin gene that give rise to alternative amino acids and so to different globin molecules.
6.5 The alpha and beta thalassaemias can be distinguished in the laboratory by abnormalities in the alpha- or beta- globin genes giving rise to abnormal alpha- or beta- globin proteins in the particular haemoglobin.
6.6 The laboratory tests that give the most precise and comprehensive information about the protein nature of a suspected haemoglobinopathy include electrophoresis and HPLC.
6.7 The principal findings in the FBC from a patient with a haemoglobinopathy are likely to be low haemoglobin and a reduced MCV.
6.8 The principal findings in the blood film from a patient with a haemoglobinopathy include microcytic and hypochromic red blood cells. In severe homozygous sickle cell disease there are likely to be sickle cells, and in both haemoglobinopathies schistocytes are likely to be present. In very severe disease, there may be polychromasia and nucleated red blood cells.
6.9 Hereditary spherocytosis and hereditary elliptocytosis can be differentiated on a blood film by the shape of the red blood cells. Complex analyses of the membranes of the cells can also be informative.
6.10 Erythrocytosis is generally taken to be raised numbers of red blood cell alone, which may be a response to hypoxia. There are also raised red cells in polycythaemia, but in this disease raised platelets and white blood cells are also present. This disease may also transform into a malignancy such as a myeloid leukaemia.