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Updated: Mar 15, 2026

A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
What Clinical Laboratorians Should Do in Response to Extremely Low Hemoglobin A1c Results
Ping Wang1,2
1Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston TX, and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York City, NY pwang@houstonmethodist.org.
Abstract:
Extremely low hemoglobin A1c (HbA1c) results below reference range are rare, and the causes and clinical implications associated with low HbA1c results are not well understood among clinical laboratorians. A case of extremely low HbA1c results was reported, in which liver cirrhosis, subacute hemorrhage and recent transfusion all contributed to the low result. This case illustrates when HbA1c should not be used as a clinically relevant diabetes marker. However, low or extremely low HbA1c (<5.0% or <4.0%) may occur in apparently healthy individuals. When this occurs, it is an independent risk factor associated with liver diseases, hospitalization, and all-cause mortality. From the clinical laboratory perspective, the clinical cause of extremely low HbA1c should be determined, and suggestions of different test utilization or increased health surveillance should be given to care providers.
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