HbA1c Below the Reportable Range

Vivek Pant, MD


Lab Med. 2022;53(2):e44-e47. 

In This Article

Abstract and Introduction


This case report concerns a 71 year old female patient who had a very low glycosylated hemoglobin (HbA1c) despite having a high level of fasting blood glucose. The patient had a decreased erythrocyte count, elevated red blood cell indices, and a reticulocyte count with no evidence of hemoglobinopathy. She reported receiving hydroxychloroquine treatment for systemic lupus erythematosus. Subsequent laboratory investigations revealed hemolysis with formation of cold agglutinin. Because cold agglutinins can interfere with HbA1c assays, the specimens were reanalyzed after warming. The complete blood count results improved, but the HbA1c result did not change. In patients in whom medications and/or medical conditions may interfere with HbA1c levels, alternative measures of glycemic control, such as fructosamine, could be beneficial.


Glycosylated hemoglobin (HbA1c) is extensively used for the screening, diagnosis, and monitoring of diabetes mellitus. It reflects an individual's glycemic control over the past 8 to 12 weeks and correlates with the development of diabetic complications. The measurement of HbA1c does not require patients to be fasting, and it has high preanalytical stability. In addition, it is more convenient in clinical practice than other measures such as fasting blood glucose or a glucose tolerance test.

Research has shown that HbA1c is formed from the posttranslational addition of glucose to the N-terminal valine of the beta chain of hemoglobin A through an Amadori rearrangement.[1] Application of HbA1c as a glycemic control indicator relies on glycation efficiency, which is determined by the integrity of globin chains and the life span of erythrocytes. Therefore, HbA1c may give false results in certain conditions (Table 1), thus warranting alternative methods to diagnose and monitor diabetes.

Apart from the hematologic and genetic conditions mentioned in Table 1, the use of certain drugs affecting the red blood cells (RBCs) may also cause a false HbA1c result (Table 2). This report highlights the limitations of using HbA1c as a diagnostic tool in a patient with hemolytic anemia further complicated by the formation of cold agglutinin. Furthermore, this report indicates that an HbA1c finding needs to be interpreted in the context of a clinical situation.