Artefactually low glycated haemoglobin is a potential pitfall in diabetes management: consider congenital haemolytic anaemias

Abstract

Measurement of glycated haemoglobin is widely used as an index of glycaemic control in the out‐patient management of diabetes mellitus. The glycated haemoglobin measurement most commonly reported by laboratories being the HbA1c. Prospective clinical trials using the HbA1c as an index of glycaemia now indicate a benchmark for both the patient and clinician in assessing their efforts to improve glycaemic control. Glycated haemoglobins are formed by a non‐enzymatic reaction between carbohydrates and haemoglobin and a multiplicity of techniques to measure them exist. A number of conditions artefactually lower the HbA1c measurement, which may lead to false reassurance that glycaemic control is good. These conditions include iron deficiency anaemia, haemoglobinopathies, chronic renal failure or recent blood transfusion. A case of congenital haemolytic anaemia is described, highlighting another potential cause of artefactually low HbA1c. If the glycated haemoglobin result is spuriously low, other methods to assess glycaemic control, including self blood glucose monitoring and fructosamine assays, should be adopted. Copyright © 2001 John Wiley & Sons, Ltd.

Falsely high glycated haemoglobin [HbA1C] because of haemoglobin OSU-Christiansborg

“…Autoimmune and congenital haemolytic anaemias (e.g. hereditary spherocytosis and elliptocytosis) are associated with low HbA1C because of reduced erythrocyte survival (Baynes, McIntosh & Feher, 2001).…”

“…On the contrary, uraemia (Baynes et al, 2001), alcohol abuse (Hoborman & Chiodo, 1982) and high-dose aspirin intake (Nathan, Francis & Palmer, 1983) cause falsely high HbA1C concentrations. Uraemia affects the results by the process of carbamylation of the B-chain although other factors such as anaemia of chronic disease may coexist.…”

Factitious Biochemical Measurements Resulting From Hematologic Conditions

“…However, HbA 1c measurement by highperformance liquid chromatography (HPLC)-based assays is inaccurate in the presence of some structurally abnormal hemoglobins. 63,70,71,[77][78][79]87,88 The extent of interference varies with the specific commercial HPLC method used and the type of abnormal hemoglobin.…”

“…70 Other variants result in overestimation of HbA 1c , eg, Hb Raleigh, 80 Hb Okayama, 70 Hb Graz, 63 HbK Woolwich, 77 Hb Osu-Christiansborg, 78 Hb Sherwood Forest, Hb South Florida, and Hb Niigata. Increased HbF, eg, in hereditary persistence of fetal hemoglobin or the rise of HbF during pregnancy may also yield factitiously higher results for HbA 1c because of coelution.…”

“…[62][63][64] In HIV+ patients, HbA 1c underestimated the glucose levels by 12.3% compared with the 3-month average fasting blood glucose levels. 64 The authors also found that the patients had low haptoglobin levels, indicating hemolysis, probably induced by nucleoside analog drugs.…”