Incidental Detection of Hb Disorders During HbA1c Analysis

Dear editor,

We read with interest the article by Lorenzo-Medina et al. published on effects of hemoglobin variants on HbA1c values measured using a high performance liquid chromatography method. ¹

HbA1c measures the exposure of hemoglobin (Hb) to the average blood glucose over the life span of a red blood cell (RBC), is an established index of glycemic control, and correlates with risk of long-term diabetic complications. However, the accuracy of HbA1c measurement can be affected by many factors. Analytical interference of Hb variants is well characterized for many HbA1c methods; less is known about RBC life span in these patients and whether the relationship between HbA1c and glycemia may be significantly different from that seen in hematologically normal individuals, thereby affecting the interpretation of the results.

Our area, Basque Country (north Spain), is considered a region of low prevalence of Hb disorders, but the presence of these diseases has increased in our area due to immigration; the incidentally detected Hb variants during HbA1c analysis runs in parallel.

HbA1c was measured with high pressure liquid chromatography (HPLC) analyzers Menarini ARKRAY ADAMS™ A1C HA-8160 Diabetes Mode (2002-2010), HA-8180V (2011-2014), and HA-8160 Thalassemia program.

In the period 2002-2014, 438 604 HbA1c analysis were performed and the number of Hb disorders detected: 600 beta thalassemia carriers, 173 alpha thalassemia carriers, 44 Hb Lepore, 12 deltabeta thalassemia, 5 HPFH, 115 HbAS, 1 HbSS, 23 HbAC, 15 HbAD, 3 HbAE, 2 HbAJ, 1 Hb Shelby.

Given the global occurrence of both Hb variants and diabetes, it is important to understand the potential impact of Hb variants on RBC survival and ultimately how the most common Hb variants may affect the clinical interpretation of HbA1c test results used in the diagnosis and management of diabetes. The idea that RBC survival in Hb S trait patients is normal can be found throughout the literature, without reference to a particular study. Data are also lacking for the remaining 3 most common Hb variants despite the widely accepted practice of using HbA1c to interpret average glycemia in diabetic patients with Hb C, Hb D, or Hb E trait. ²

The characteristic dynamic of eryptosis in iron deficiency anemia and thalassemia trait has been defined, which demonstrates that not only ineffective erythropoiesis but also altered RBC life span is present in thalassemia carriers. ³

Hb disorders may invalidate the results of HbA1c, resulting in missed diagnosis, misdiagnosis, or mismanagement of the patient. From that point of view HPLC has the advantage to detect the presence of Hb variants, which must be reported to the clinician, with the advice to interpret the result with caution to ensure appropriate patient management. ⁴ For situations in which the HbA1c values are unreliable, measurement of other glycated proteins (fructosamine or glycoalbumin) provides appropriate alternative to monitor therapy.