Hemoglobin Wayne Variant Interfering with Hemoglobin A1c Measurement

Presentation Number: SAT 617
Date of Presentation: April 1st, 2017

Maali M Milhem*1, Mose July2, Shahed Elhamdani3 and Nesreen Aburrahman BenHamed4
1Marshall University, ona, WV, 2Marshall university school of medicine, Huntington, WV, 3Marshall University, Barboursville, 4Marshall University, Barboursville, WV



According to the American Diabetes Association since 2010, diabetes mellitus can be diagnosed based on two consecutive measurements of A1c ≥6.5%. However, it is known that certain hemoglobin abnormalities can confound A1c measurements through various mechanisms. We present a case of falsely elevated A1c levels due to the rare hemoglobin Wayne variant.

Case presentation:

A 67-year-old female patient was referred to endocrinology clinic for management of uncontrolled diabetes mellitus (DM). She was diagnosed with type 2 DM nine years ago, and was started on glipizide by her primary care physician, which was titrated up to 10mg daily. At initial endocrine visit, her A1c was 11.6;multiple repeat A1c consistently showed her to be >11 %. As part of diabetes management, she was asked to log her blood glucose levels regularly. Two things of note were found after reviewing her blood glucose log. First, the patient had frequent hypoglycemic episodes. Second, a discrepancy was found between her A1c levels and her blood glucose readings, which were ranging from 54 to 128 mg/dl. Due to recurrent hypoglycemic episodes, glipizide was titrated to 2.5mg daily and then stopped altogether when she reported several episodes of severe hypoglycemia. Metabolic workup was performed, which found hemoglobin, kidney, liver enzymes, and lipids were within normal quantitative limits. Fructosamine level was within normal limit. During this entire workup, the patient insisted that she was following physician recommendations and prescriptions properly. It was at this point that we shifted our attention to a potential confounder. Hemoglobin electrophoresis was ordered to look for hemoglobinopathies; the results showed that our patient had a hemoglobin Wayne trait. When A1c was repeated with the appropriate immunoassay, her A1c was actually 6.2%.


Four basic types of methods are used commonly to measure HbA1c: immunoassay, ion exchange high-performance liquid chromatography (HPLC), boronate affinity HPLC, and enzymatic assays. Hemoglobin Wayne variant caused inaccuracy because of the interference with the general assay method that was used. At our facility, A1c is measured by ion exchange HPLC using the BioRad Variant analyzer. This method has been shown to be susceptible to inaccuracy in the presence of hemoglobin variants. A1c was repeated with Roche (Tina Quant) immunoassay, which usually gives more accurate results in patients with hemoglobin variants. 

This case not only presents this rare and interesting hemoglobin variant but also reminds providers that A1c testing is susceptible to misinterpretation due to multiple interfering factors. With the proper awareness and improved patient-physician communication, providers may avoid the mismanagement of both diabetic and nondiabetic patients and avoid risk of hypoglycemia through unnecessary antihyperglycemic medications.


Nothing to Disclose: MMM, MJ, SE, NAB