A-163 Abnormal HbA1c Results Lead to an Unexpected Chronic Myeloid Leukemia Diagnosis
Authors: Mathewson N J , Pearson L N , Doyle K 
Published: September 2023

Abstract

Background
Hemoglobin A1c (HbA1c) is used to assess and monitor glycemic control, as it reflects average levels of blood glucose over the previous two to three months. HbA1c can be measured by capillary electrophoresis (CE) which calculates percent HbA1c from the HbA1c and HbA peaks in the electropherogram. CE is a prominent method in reference labs as it provides complete automation with fast separation and less interference than what can be observed with other assay formats. The high-resolution capability of CE allows the quantification of HbA1c, even in the presence of labile HbA1c, carbamylated and acetylated hemoglobins, and major hemoglobin variants. These variants are commonly recognized as causes of interference in HbA1c measurements.

Case presentation
A 70-year-old male with a history of type 2 diabetes mellitus presented to an outpatient laboratory for routine venipuncture to evaluate glycemic management and cardiovascular disease risk. HbA1c analysis by CE resulted with a flag for an atypical profile in the electropherogram and no HbA1c value was reported. HbA1c measurements throughout the past year demonstrated HbA1c values ≥6.5% yet trending downward, consistent with his diagnosis and treatment of diabetes mellitus. HbA1c was repeated with a different instrument and fresh specimen collected at a different phlebotomy location and showed similar inconclusive results. Unusual shifts in hemoglobin peak migration times were observed upon close review of the electropherogram, suggesting a potential analytical interference of the HbA1c measurement.

Results
Because atypical peak migration times due to elevated leukocyte counts or increased viscosity are documented by the manufacturer, a follow up complete blood count (CBC) was recommended for this patient. CBC results revealed a highly elevated leukocyte count of 175.80 k/μL (reference interval: 4.30–11.30 k/μL), suggesting the abnormal HbA1c migration profile was possibly due to leukocytosis. The elevated leukocyte count led the patient to visit an oncology clinic where leukemia/lymphoma phenotyping, ancillary studies, and cytogenic testing, confirmed a diagnosis of chronic myeloid leukemia. The diagnosis was completely unexpected, as the patient’s only complaint was feeling fatigued over the last few weeks. The patient began chemotherapy treatment immediately.

Conclusion
The present case is an example of how leukocytosis and hyperviscosity can interfere with HbA1c measurement by CE. Although this specific clinical situation is uncommon, clinicians and laboratorians should be aware of these potential interferences, as they have not been discussed in detail in the literature. Further, these interferences warrant recognition in the cancer patient population, as this population may be directly impacted by elevated leukocyte count and hyperviscosity in their specimens, which may impact glycemic control monitoring during treatment. The incidence of diabetes in cancer patients is six times greater than in the general population, making glycemic control monitoring key for cancer patients. Many diabetic patients undergoing chemotherapy will prioritize their cancer treatment over management of their diabetes, which increases their risk for poor glycemic control. These patients should be carefully monitored to ensure HbA1c results are accurate as poor glycemic control can lead to increased risk for infections and hospitalizations, which may decrease survivorship.