Haemoglobinopathy diagnosis: Algorithms, lessons and pitfalls

Diagnosis of haemoglobinopathies, including thalassaemias, can result from either a clinical suspicion of a disorder of globin chain synthesis or from follow-up of an abnormality detected during screening. Screening may be carried out as part of a well defined screening programme or be an ad hoc or opportunistic test. Screening may be preoperative, neonatal, antenatal, preconceptual, premarriage or targeted at specific groups perceived to be at risk. Screening in the setting of haemoglobinopathies may be directed at optimising management of a disorder by early diagnosis, permitting informed reproductive choice or preventing a serious disorder by offering termination of pregnancy. Diagnostic methods and algorithms will differ according to the setting. As the primary test, high performance liquid chromatography is increasingly used and haemoglobin electrophoresis less so with isoelectric focussing being largely confined to screening programmes and referral centres, particularly in newborns. Capillary electrophoresis is being increasingly used. All these methods permit only a presumptive diagnosis with definitive diagnosis requiring either DNA analysis or protein analysis, for example by tandem mass spectrometry.