From the Guidelines
A low Hemoglobin A1c (HbA1c) over 3 months combined with leukopenia (low white blood cell count) suggests several possible underlying conditions that require medical evaluation, and the most recent guidelines from 2025 recommend careful interpretation of HbA1c results in the context of other clinical findings 1. This combination may indicate bone marrow suppression, nutritional deficiencies, certain medications' side effects, or hematologic disorders. Low HbA1c (below 4%) doesn't necessarily mean good glycemic control but could reflect increased red blood cell turnover, shortened red blood cell lifespan, or hemolytic anemia, as noted in studies on the clinical application of HbA1c testing 1. The leukopenia component points to potential bone marrow dysfunction or autoimmune processes. Patients with this combination should undergo comprehensive blood work including:
- Complete blood count with differential
- Peripheral blood smear
- Vitamin B12 and folate levels
- Liver and kidney function tests
- Possibly bone marrow examination, as recommended for accurate diagnosis and management of diabetes and related conditions 1. Treatment depends on identifying the underlying cause - whether it's medication adjustment, nutritional supplementation, or management of an underlying condition like hypersplenism or autoimmune disorders. This combination of findings warrants prompt medical attention as it may indicate serious underlying pathology affecting multiple blood cell lines. The relationship between these two findings stems from their shared connection to blood cell production and lifespan dynamics, highlighting the importance of integrated care and consideration of all relevant clinical and laboratory findings in patient management 1.
From the Research
Low Hemoglobin A1c (HGA1c) and Leukopenia
- A low HGA1c level over 3 months with leukopenia can be an indication of several underlying conditions, and it is essential to consider the clinical context and other laboratory results to determine the cause.
- Leukopenia, a reduction in white blood cell count, can be caused by various factors, including bone marrow disorders, autoimmune diseases, and certain medications 2, 3, 4.
- A low HGA1c level may not always indicate good glycemic control, as it can be influenced by factors such as red blood cell lifespan and hemoglobinopathies 5.
Potential Causes of Low HGA1c and Leukopenia
- Bone marrow disorders, such as aplastic anemia or myelodysplastic syndrome, can cause both leukopenia and a low HGA1c level due to impaired production of blood cells 2, 4.
- Certain medications, such as those used to treat cancer or autoimmune diseases, can cause leukopenia and affect HGA1c levels 3, 4.
- Hemoglobinopathies, such as sickle cell disease or thalassemia, can affect HGA1c levels and cause leukopenia 5.
Clinical Implications
- Patients with low HGA1c and leukopenia should be evaluated for underlying conditions that may be causing these abnormalities.
- A comprehensive laboratory workup, including complete blood counts, blood smears, and hemoglobin electrophoresis, may be necessary to determine the cause of low HGA1c and leukopenia 2, 3, 4, 5.
- Clinicians should be cautious when interpreting HGA1c values, as they can be influenced by various factors, and consider the clinical context and other laboratory results when making treatment decisions 5.