Hemoglobinopathy Evaluation in Routine Carrier Testing: Results to Inform Guidelines and Protocols [5O

Abstract

INTRODUCTION: ACOG guidelines recommend red blood cell indices followed by hemoglobin electrophoresis to assess carrier status for hemoglobinopathies. However, data is limited on outcomes of these recommendations, and the role of DNA testing. METHODS: Our database was queried for abnormal hemoglobin evaluations from 42,166 consecutive samples of mixed ethnicities. Hemoglobin evaluation consisted of red blood indices and, high-performance liquid chromatography followed by, if necessary, hemoglobin electrophoresis. A subset (n= 2,863) also had DNA genotyping. Abnormal reports were evaluated individually, and test metrics and interpretations were tabulated. RESULTS: Of the 42,166 samples, 2,278 (5.4%) had abnormal hemoglobin evaluation results. Of the 2,278 abnormal results, the most common interpretation (32%) was 'possible alpha thalassemia trait', followed by 'sickle cell trait' (22%), 'possible beta thalassemia trait' (10%), 'elevated hemoglobin F' (10%), and 'hemoglobin C trait' (5%). Of the 2,863 samples that had genotyping, 146 (5.1%) had abnormal molecular results. Genotyping confirmed 100% (5/5) of samples with abnormal hemoglobin evaluation indicating 'consistent with alpha thalassemia trait' and 41% (17/41) indicating 'possible alpha thalassemia trait'. Sixteen percent (14/89) of samples with abnormal molecular results, and normal hemoglobin evaluation for alpha thalassemia, were silent alpha thalassemia carriers. CONCLUSION: Our study estimates a 5% positivity rate for hemoglobin evaluation. However, some results are non-specific and require molecular follow up. Forty-one percent of hemoglobin evaluation results interpreted as 'possible alpha thalassemia trait' were confirmed as genetic carriers. Concurrent DNA testing provides information and results more quickly to patients, and better identifies those patients truly at risk to be carriers of alpha thalassemia.