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Updated: Jun 29, 2025

A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Leading digit bias in hemoglobin thresholds for red cell transfusion
Sheharyar Raza1,2, Malcolm Risk3, Christine Cserti-Gazdewich1,4
1Division of Hematology, University of Toronto, Toronto, Canada.
Background:
Leading digit bias is a heuristic whereby humans overemphasize the left-most digit when evaluating numbers (e.g., 9.99 vs. 10.00). The bias might affect the interpretation of hemoglobin results and influence red cell transfusion in hospitalized patients.
Study Design And Methods:
Adults who received a red cell transfusion while registered at the University Health Network (Toronto, Canada) between January 1, 2016 and January 1, 2022 (n = 6 years) were included. The primary analysis excluded apheresis, red cell disorders, radiology suites, and operating rooms. The primary comparison was a regression discontinuity analysis of transfusion occurrence above and below the hemoglobin threshold of 79 g/L (local units). Additional analyses tested other leading digit and control thresholds (71, 81, and 91 g/L). Secondary analyses explored temporal covariates and clinical subgroups.
Results:
A total of 211,872 red cell transfusions were identified over the study period (median pre-transfusion hemoglobin 76 g/L; interquartile range = 69-92 g/L), with 107,790 inpatient transfusions in the primary analysis. The 79 g/L threshold showed 815 fewer red cell units above the threshold (95% confidence interval [CI]: -1215 to -415). The 69 g/L threshold showed 2813 fewer transfused units (95% CI: -4407 to -1220), and 89 g/L showed 40 fewer units (95% CI: -408 to 328). The effect was accentuated during daytime, weekday, and May-June months, persisted in analyses including all transfusions, and was absent at control thresholds.
Conclusion:
Leading digit bias might have a modest influence on the decision to transfuse red cells. The findings may inform practice guidelines and quasi-experimental study design in transfusion research.
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