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This is certainly a difficult one. I go along with Chris' view about us being asked for a consult on the sample and of doing 'whatever is reasonable to answer the question put to us'. I certainly have no qualms about adding on tests which are of relevance to the condition being investigated (adding thyroid antibodies onto a TFT is an example), but if the request is to assess glycaemic control, then the question did not ask us to test for the completely unrelated condition of haemoglobinopathy. It just so happens that our best test of glycaemic control involves haemoglobin, but I am sure the patient with diabetes does not realise that! Interestingly, yesterday our haematologist did not have a problem about adding on Hb electrophoresis either. Having slept on it, he is now not so keen! Eric ----- Original Message ----- From: Chris Florkowski <[log in to unmask]> To: <[log in to unmask]> Sent: Wednesday, June 25, 2003 10:26 PM Subject: Haemoglobin variants in HbA1c samples Our haematologists have never had a problem test-adding Hb electrophoresis - the question of a "genetic test" has not arisen in this context. The ultimate arbiter is mass spectrometry, in our domain and under our jurisdiction. To answer Eric's specific point, we take the view that any request that crosses our threshold is a consultation and we will do (test-add) whatever is reasonable to answer the question put to us. We turned up one especially interesting Hb variant this way (vide infra for precis), for which we did get permission from the patient to publish the findings. Chris Florkowski; Christchurch, NZ C M Florkowski, T A Walmsley, S O Brennan and P M George Haemoglobin Marseille-Long Island and interpretation of HbA1c: which HbA1c result is the "right answer"? Postgraduate Med J (2003) 79:174-175 An asymptomatic 44 year old woman was screened for diabetes. Initial HbA1c analysis by HPLC (Bio Rad Variant) gave a result of 45%, considered biologically implausible. Immunoassay (DCA 2000) was 2.8%, also considered implausible. Affinity chromatography (Primus Corporation, Kansas City, MO, USA) gave 4.6%. Mass spectrometry (VG Platform; Micromass, UK) confirmed the presence of Hb Marseille-Long Island (methionyl extension of the amino terminus of the ß globin chain and histidine to proline substitution at position 2 in the ß chain) This substitution of a positively charged amino acid with a neutral one results in a net loss of one positive charge. It thus has lower affinity for the ion exchange resin and coelutes with the HbA1c peak resulting in an artefactually high reading. The ß globin chains from Hb Marseille-Long Island have an amino terminal that is modified in a way that does not permit recognition by the antibodies of the DCA 2000 assay. Given that the subject is heterozygous for this variant and that half the ß chains are therefore normal, then arguably the "correct" answer might be obtained by doubling the DCA 2000 result. This would give a value of 5.8%, which is plausible. ********************************************************************** ** This email and attachments have been scanned for content and viruses and is believed to be clean ** This email or attachments may contain confidential or legally privileged information intended for the sole use of the addressee(s). Any use, redistribution, disclosure, or reproduction of this message, except as intended, is prohibited. If you received this email in error, please notify the sender and remove all copies of the message, including any attachments. Any views or opinions expressed in this email (unless otherwise stated) may not represent those of Canterbury District Health Board ********************************************************************** ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/ ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/