HbC Revealed in A1C Assay: A Lesson Learnt From a Routine Health Checkup
Published Jul 3, 2020 · S. Sreeram, Drishti Gupta, Sridevi Hanaganahalli Basavaiah
Journal of Diabetes Science and Technology
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Abstract
Glycated hemoglobin (HbA1c) provides an average blood glucose concentration over the erythrocyte lifespan. It is a biochemical marker for the management of diabetes mellitus. It helps to monitor long-term glycemic control and assess the risk of developing complications. Of late, its importance in diagnosis is also established and treatment goals have been set.1 However, conditions affecting the structure of hemoglobin (Hb) or lifespan of red blood cells affect the normal values.2-4 Hence the test must be advocated and interpreted judiciously. A 57-year-old man from Africa visited our hospital for health checkup, which included a battery of tests, namely, fasting/postprandial blood glucose, liver and renal function tests, thyroid profile, complete hemogram, HbA1c estimation, and fecal and urine routine examination. The laboratory results revealed an abnormal lipid profile (total cholesterol: 243 mg/dL, triglycerides: 154 mg/dL, high-density lipoprotein [HDL] cholesterol: 38.2 mg/dL, low-density lipoprotein [LDL] cholesterol: 173.4 mg/dL, and TC/HDL ratio: 6.36) and a raised gamma glutamyl transferase (88.4U/L) with minimal elevation of red cell distribution width (15.2). However, peripheral smear examination was not performed. The HbA1c (BIO-RAD D10; high performance liquid chromatography [HPLC]) value was 4.7% without any flags and correlated well with plasma glucose. To our surprise, HbC window of 26.7% and HbA064% were seen. The sample was then run on Variant analyzer (BIO-RAD Dual D10). A detailed result was obtained with HbA1c: 5%, A0: 50.9%, A2: 3.5%, HbS: 3.1%, and HbC: 35%. Based on this test, the case was concluded as HbC variant in the patient with β-thalassemia. People with HbC are phenotypically normal with no evident clinical symptoms. They have normal hemoglobin concentration and reticulocyte count.5 The red cell mass and red cell survival may both be decreased. Lower oxygen affinity of HbC facilitates sufficient oxygen delivery to tissues. HbC is of clinical significance when inherited with HbS (HbSC) or with β-thalassemia (HbC-β-thalassemia). Genetic counseling and anticipatory guidance play a pivotal role in patients with HbC trait.4 There are >20 methods for the detection of A1C in the laboratory. Data reveal that approximately 14% labs are using methods that show interference of Hb variants in the A1C levels.6 In this case A1C assayed by HPLC was consistent, reliable with no interference from HbC. As per the manufacturer’s guidelines, A1C values are reportable with heterozygous HbC and only values of ≥60% are not reportable.2,4,5 It is also recommended that an isolated A1C increase should be correlated with fasting blood glucose levels in a person not known to have diabetes. Patients need to be screened for hemoglobinopathy in the event of discordant blood glucose and A1C values. A fructosamine test may be more reliable in patients who have hemoglobinopathies.6 In this era of population migration and globalization, hemoglobinopathies are diagnosed even in area non-endemic to the same. Health care providers should be well informed about the A1C assay methods. National Glycohemoglobin Standardization Program–certified assays are recommended for standardized results of A1C. Immunoassays can show positive bias for hemoglobin variants HbC in A1C assays. This can lead to unnecessary rigorous dietary control and hypoglycemia in patients with HbC. Thus, A1C assays for diagnosis of diabetes need to be interpreted with caution in areas endemic for hemoglobinopathy.