Can lymphocytic leukemia cause a low Hemoglobin A1c (HbA1c)?

Lymphocytic Leukemia Can Cause a Low Hemoglobin A1c (HbA1c)

Yes, lymphocytic leukemia, particularly chronic lymphocytic leukemia (CLL), can cause falsely low HbA1c values due to shortened red blood cell lifespan.

Mechanism of Low HbA1c in Lymphocytic Leukemia

• HbA1c values reflect glycemia over the preceding 120 days, with approximately 50% determined by blood glucose levels in the month prior to measurement, 25% from 30-60 days before, and 25% from 60-120 days before measurement 1

• Any condition that shortens erythrocyte lifespan decreases HbA1c values, since glycation of hemoglobin increases with the age of red blood cells 1

• Chronic lymphocytic leukemia can cause hemolytic anemia or otherwise reduce red blood cell survival, leading to falsely low HbA1c readings that do not accurately reflect actual glycemic control 1

Evidence of HbA1c Interference in CLL

• A 2022 case report specifically documented unexpectedly low HbA1c in a patient with chronic lymphocytic leukemia, suggesting that the marked number of neoplastic lymphocytes may interfere with enzymatic HbA1c assays 2

• Advanced CLL (Binet stage C) is characterized by anemia (hemoglobin <10 g/dl) and/or thrombocytopenia, which can affect HbA1c measurements 1, 3

Clinical Implications

• When evaluating HbA1c in patients with lymphocytic leukemia, clinicians should be aware that values may be falsely low and not representative of true glycemic control 1, 2

• A hemoglobin variant or interference should be suspected if the HbA1c reading is surprisingly low or significantly changed coincident with a change in laboratory method 1

• In patients with CLL and suspected HbA1c interference, alternative methods for monitoring glycemic control should be considered:

  • Self-monitoring of blood glucose (SMBG) 1
  • Fructosamine or glycated albumin measurements
  • Continuous glucose monitoring when available

Other Conditions That May Affect HbA1c

• Besides lymphocytic leukemia, other conditions that can decrease HbA1c include:

  • Kidney disease 1
  • Liver disease 1
  • Hemolytic anemia 1
  • Hemoglobinopathies 1
  • Recovery from blood loss 1
  • Pregnancy 1

• Conversely, conditions that slow erythropoiesis, such as iron-deficiency anemia and aplastic anemia, can increase HbA1c by causing an older erythrocyte cohort 1

Laboratory Considerations

• When HbA1c values are unexpectedly low in a patient with lymphocytic leukemia, consider using a boronate affinity chromatography method of measuring HbA1c, which may be more reliable in the presence of interfering factors 1

• The National Glycohemoglobin Standardization Program (NGSP) provides resources for addressing potential interferences in HbA1c testing 1

• In cases of suspected interference, correlation with other glycemic measures (fasting glucose, post-prandial glucose) is essential to establish true glycemic status 1