Findings demonstrate a need to enhance glycemic control in sickle cell disease, suggesting better testing protocols.
Background Hemoglobin A1c (HbA1c) cannot be accurately measured in patients with Sickle Cell Disease (SCD) or other homozygous/compound heterozygous hemoglobin variants due to low or absent Hemoglobin A and increased red blood cell (RBC) turnover, which affects hemoglobin glycation rates. In patients receiving RBC transfusions, a common SCD treatment, HbA1c results are further confounded by donor HbA1c levels. Fructosamine, which measures glycated serum proteins, has emerged as a valuable alternative for monitoring long-term glycemic control in this population because it is independent of Hemoglobin A. To promote appropriate test utilization, our laboratory cancels HbA1c results when a homozygous/compound heterozygous hemoglobin variant is detected and recommends fructosamine testing for long-term glycemic monitoring. Purpose This study aims to assess the effectiveness of our HbA1c cancellation and recommendation protocol and identify opportunities to improve diabetes diagnosis and glycemic monitoring in affected patients. Methods Laboratory data from January 1, 2024, to December 31, 2024, were reviewed to identify instances where HbA1c tests were canceled due to homozygous/compound heterozygous hemoglobin variants detected by High-Performance Liquid Chromatography (HPLC) using the Bio-Rad D-100 analyzer. Electronic Medical Records (EMRs) were reviewed to determine whether fructosamine tests were subsequently ordered. Patient demographics and clinical data were analyzed to assess the risk of inadequate glycemic control in cases without follow-up fructosamine testing. Results Among 277,448 reported HbA1c results, 46 tests from 42 unique patients were canceled due to the presence of homozygous/compound heterozygous hemoglobin variants. The mean age of these patients was 49.7 years. Of these, 69.0% had known SCD (Hb SS, Hb SC, or Hb S/beta-thalassemia), 71.4% were female, and 92.8% were Black or African American. Additionally, 23.8% had received RBC transfusion therapy. While all 42 patients had documented blood glucose measurements, only 6 instances (13.0%) showed follow-up fructosamine test, with 50% showing abnormally high levels. Furthermore, 31 patients (73.8%) likely would have benefited from fructosamine testing due to a known diabetes diagnosis or at least one documented glucose level of 101 mg/dL or higher. Among these 31 patients, 24 were monitored for urine albumin-creatinine ratio, with 48.4% showing abnormal results. Discussion This study suggests that patients with SCD are not consistently monitored for long-term glycemic control, which increases the risk of undiagnosed or poorly managed diabetes. Laboratory interventions, such as adding alerts or notifications to the Electronic Medical Record, may help improve fructosamine testing rates and diabetic management in this vulnerable population.
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Snyder et al. (2025) studied this question.
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