Hemoglobinopathies May Distort HbA1C – A Caution to Practitioners

Measuring glycated hemoglobin (HbA1c) gives us a patient’s long term average blood glucose levels.¹

Since HbA1c measures the percentage of patients’ glycosolated hemoglobin, patients who possess variants of hemoglobin can exhibit false readings. Such variants, called hemoglobinopathies, can include inherited hemoglobin variants, elevated fetal hemoglobin, and hemoglobin S and E which are prevalent in people of Southeast Asia, Mediterranean, and African descent. ² One variant of particular concern is the sickle cell trait. People with this trait have inherited biological differences affecting the formation of their hemoglobin and erythrocytes, which in turn affects their levels of glycated hemoglobin. ⁵

People who have the sickle cell trait have both normal hemoglobin A and hemoglobin S. In the U.S., African Americans are at a higher risk of having the sickle cell trait, and approximately 18.7 percent of African Americans who are 20 years and older have diabetes. ² In people who have both the sickle cell trait and diabetes, about 1 million people in the U.S., using HbA1c to measure blood glucose levels can be prone to anomalies. People with these hemoglobin variants can have falsely low or high levels which can lead to improper treatment including: HbA1c readings that are different than expected; HbA1c levels that are extremely different from previous HbA1c readings; or low correlations between HbA1c and self-monitored glucose levels. ²

Normally, for every 25-32mg/dL increase in blood glucose levels, there is a 1% increase in HbA1c in patients without any hematologic variants. ³ But with patients who do have any hematologic disorders, this corresponding increase in HbA1c does not occur.

In a published article regarding sickle cell and diabetes, an African American woman with both type 2 diabetes and sickle cell disease, had blood glucose levels ranging from 50 to 320mg/dL yet her HbA1c was consistently <6%. ³ Due to this inaccuracy, other measures of glycemic control such as fructosamine should be considered as a suitable assessment of long term blood glucose levels in patients who have both diabetes and sickle cell. ³ Fructosamine can be easily measured using a home glucose monitor. ³ It is a simple, low cost test that corresponds well to actual blood glucose levels in the body.

In another article concerning the sickle cell trait and HbA1c, two African American patients with type 2 diabetes who control their blood glucose levels with diet and oral medications, had two different HbA1c results. ⁴ Patient A did not possess any hemoglobin variants and had an average blood glucose level of 103mg/dL with an HbA1c of 5.7%. This A1c level corresponded well with the average glucose levels. Patient ASF, however, possessed the sickle cell trait and had an average blood glucose of 130mg/dL and a HbA1c of 4.7%. This blood glucose measurement does not correspond with Patient ASF’s A1c level. For a blood glucose level of 130mg/dL, the HbA1c should fall a little above 7.0%.

HbA1c should be relied upon with great caution in patients who carry these hemoglobinopathies. Even though some HbA1c assays are not influenced by these hemoglobin variants, these patients may suffer from other blood related diseases that may affect HbA1c such as transfusions requirements or anemia. ² Heavy bleeding, kidney failure and liver disease can also produce false A1c results. ² Of the 20 most commonly used methods to measure A1c there are three, the Abbott Architect/Aeroset, Bayer A1c NOW and Beckman AU system, that result in false HbA1c readings due to the sickle cell trait. ¹ Various testing methods such as Axis-Shield Afinion, Beckman Synchron System, Bio-Rad Variants and Ortho-Clinical Vitros can be used to measure HbA1c without interference from the sickle cell trait. ¹

1. HbA1c methods: Effects of Hemoglobin Variants (HbC, HbS, HbE and HbD traits) and Elevated Fetal Hemoglobin (HbF). Harmonizing Hemoglobin A1c Testing. NGSP, 2013 July. 24 July 2013.
2. “Sickle Cell Trait and Other Hemoglobinopathies and Diabetes: Important Information for Providers.” National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Diabetes Information Clearinghouse, 2012 October. 23 July 2013.
3. Kosecki, Sheri M, Rodgers, Philip T et al. “Glycemic Monitoring in Diabetics with Sickle Cell Plus β-Thalassemia Hemoglobinopathy.” The Ann of Pharmacother. Volume 39, Issue 9 (2005):1557-1560.
4. Behan, Kristina J, Merschen, Jane. “HbA1c does not always estimate average glucose.” Clinical Laboratory Science. American Society for Clinical Laboratory Science 22 March 2011. 24 July 2013. < https://www.freepatentsonline.com/article/Clinical-Laboratory-Science/277271055.html>
5. Blyer AJ, Vidya S et al. “The impact of sickle cell trait on glycated haemoglobin in diabetes mellitus.” Diabetic Medicine, Wiley Online Library. Volume 27, Issue 9 (2010): 1012-1016.

 

— Natasha Patel, PharmD Candidate, LECOM College of Pharmacy