The laboratory diagnosis of haemoglobinopathies

The laboratory diagnosis of haemoglobinopathies, including the thalassemias, is of growing importance, particularly because of an increasing requirement for antenatal diagnosis of significant disorders of globin chain synthesis. This guideline discusses the laboratory tests which are most useful in the diagnosis of haemoglobinopathies and describes their role in specific clinical circumstances. Of the newer technical methods, high-performance liquid chromatography (HPLC) is of considerable importance whereas isoelectric focusing (IEF) and immunoassay for variant haemoglobins have a more minor role. Specific recommendations have been formulated for testing in relation to genetic counselling and for neonatal diagnosis. Methods used in specialized laboratories for fetal diagnosis have been tabulated. Genetic counselling requires: (i) identification of haemoglobins S,C, D-Punjab, O-Arab, E, Lepore and H and (ii) the detection of carriers of alpha-degrees and beta thalassemia. It is recommended that subjects of all ethnic groups be screened for Beta-thalassemia trait, all except Northern European Caucasians for variant haemoglobins, and selected ethnic groups for alpha-degree-thalassemia trait. Testing for beta-thalassemia trait should be carried out when the mean cellular haemoglobin (MCH) is less-than 27 pg and testing for alpha-degree-thalassemia trait should be considered when the MCH is less-than 25 pg. Appropriate methods include HPLC or haemoglobin electrophoresis for identification of variant haemoglobins and HPLC or microcolumn chromatography for quantification of haemoglobin A2.