Haemoglobinopathies

The concept of diagnosing haemoglobinopathies is not dissimilar to investigating bone marrow pathology - it requires integration of various methods which will inform of the specific haemoglobin abnormality. In marrows the aspirate, trephine and sometimes other investigations are required to reach a diagnosis; and in haemoglobinopathy screening it may require the sickle solubility test, HPLC, haemoglobin electrophoresis, isoelectric focusing and genotyping to find the precise haemoglobin abnormality.

In practice this may not be essential as most variants are not pathological and simply an HPLC plus Hb electrophoresis may be sufficient to give a probable diagnosis. The gold standard would be to request genotyping on a sample - but these are expensive tests and commonly not required.

Here is a link for the guidelines regarding haemoglobinopathy screening as recommended by the BCSH.

Although rare - hyperhaemolysis is also a topic worth reading - attached is a link to an editorial from Dr Nay Win, NHSBT consultant in Tooting, London.

In summary:

• If suspected sickle cell disease - a sickle solubility test and appropriate bands eluting on HPLC (e.g. HbSS/HbSC) should be sufficient for the diagnosis
• If any other haemoglobinopathy - HPLC plus Hb electrophoresis is required - and any other further testing if deemed clinically necessary.

Red cell disorders are frequently examined in multiple parts of the exam so ensure you have enough exposure to these techniques to be able to answer the questions quickly.

Remember:

HbA = 2 alpha and 2 beta chains

HbA2 = 2 alpha and 2 delta chains

HbF = 2 alpha and 2 gamma chains

Delta-beta thalassaemia trait = one defective copy of the gene of the two inherited means a failure of production of delta and beta globin chains in that copy (results in slightly raised HbF and normal HbA2 - i.e. if delta chain production is decreased, this will also decrease the overall amount of HbA2 present). The remaining copy of the gene continues to produce beta and delta chains as normal. A patient article here briefly explains the condition in simple form. The following table explains which of the common haemoglobin variants may produce a pathological disorder combined with delta-beta thalassaemia trait and which may be non-pathological:

HPLC

Hb electrophoresis

Links to practice questions