Diagnostic Use
Notice of Updated HbA1c Dx threshold from 1 7 26 – guidance for health sector – HNZ – rec 15 4 26
Haemoglobin A1c is an index of metabolic control in patients with diabetes mellitus.
The result correlates best with the mean level of blood glucose during the previous 8 weeks, with the mean blood glucose during the last 30 days prior to testing contributing about 50% of the final result.
HbA1c is formed continuously during the lifespan of the RBC. The HbA1c level depends on (a) the average glucose level , (b) the mean RBC age, and (c) other factors which are not well understood but which are constant for an individuial.
Unexpectedly low HbA1c occurs when there is increased RBC turnover (reduced mean RBC age):
– Ongoing blood loss, with replacement, e.g. GI bleeding, menorrhagia, venesection
– Haemolysis
– Unstable haemoglobin (e.g. some haemoglobinopathies, thalassaemias)
– Renal failure (red cell lifespan shortened up to 40%)
– Starting iron, B12 or folate in deficient patients or starting erythropoietin in renal failure patients
– Recent transfusion
– Pregnancy
– HIV-infected patients on antiretrovirals
Unexpectedly high HbA1c occurs when there is increased mean red cell age:
– Nutritional iron deficiency
– Hyposplenism
– Bone marrow failure
These influences mean that interpretation of the HbA1c level should always be in the context of other clinical and laboratory data.
Analytical Issues
Some variant haemoglobins produce erroneous HbA1c results which are often method specific. The possibility of an analytical artefact should be considered when:
– Widely varying results between different laboratories (which may be using different methods)
– Extreme HbA1c results (e.g. over 150 mmol/mol, or below 30 mmol/mol)
– Lack of apparent correlation between HbA1c and repeated glucose results
– Known haemoglobinopathy or presence of significant amounts of HbF. Please check with Chemical Pathologist at Biochemistry laboratory, on ext 58519 re: if the analytical method used is affected by your patient’s haemoglobinopathy.
Other than mean glucose/time in range data from continuous glucose monitoring, alternative markers like Fructosamine (serum) or Glycated Albumin (serum/EDTA plasma) can be used for DM monitoring – recommend discussion with Chemical Pathologist before blood collection.
Test Method
Principle: Enzymatic
Reagents: Siemens Atellica CH Enzymatic Hemoglobin A1c
Analyser: Siemens Atellica CH
Principle: Latex Immunoagglutination
Reagents: Siemens DCA HbA1c Reagent Cartridge
Analyser: Siemens DCA Vantage
Limitations / Interference
The Atellica CH A1c_E assay has significant interference with fetal hemoglobin (HbF). Samples containing HbF may produce a negative bias (lower than actual results) with the Atellica CH A1c_E assay. Hemoglobin A1c results are invalid for patients with abnormal amounts of HbF, including those with known Hereditary Persistence of Fetal Hemoglobin.
The Atellica CH A1c_E assay should not be used to diagnose diabetes during pregnancy. Hemoglobin A1c reflects the average blood glucose levels over the preceding 8-12 weeks (the average life span of a red blood cell) and therefore may be falsely low during pregnancy or any other condition associated with recent onset of hyperglycemia and/or decreased red blood cell survival.
The Atellica CH A1c_E assay should not be used to diagnose or monitor diabetes in patients with the following conditions: hemoglobinopathies except as demonstrated to produce acceptable performance (such as sickle cell trait), abnormal red blood cell turnover (such as anemias from hemolysis and iron deficiency), malignancies, and severe chronic hepatic and renal disease.
Any cause of shortened red blood cell survival (for example, hemolytic anemia or other hemolytic diseases, pregnancy, or recent significant blood loss) will reduce exposure of red blood cells to glucose with a consequent decrease in HbA1c values. HbA1c results are not reliable in patients with chronic blood loss and consequent variable erythrocyte life span.
Fetal hemoglobin (HbF) consists of 2 alpha and 2 gamma chains that are not recognized by the FPOX enzyme which measures N-terminal fructosyl dipeptides on the beta-chain. Samples that contain high amounts of HbF, usually found in some people with thalassemia, in infants, and in some pregnant women, may yield a lower than expected HbA1c result with this assay.