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Updated: Dec 23, 2025

A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Using arterial-venous oxygen difference to guide red blood cell transfusion strategy
Alberto Fogagnolo1, Fabio Silvio Taccone2, Jean Louis Vincent2
1Department of Morphology, Surgery and Experimental Medicine, Section of Anaesthesia and Intensive Care, Azienda Ospedaliera-Universitaria Sant' Anna, University of Ferrara, 8, Aldo Moro, 44121, Ferrara, Italy.
Background:
Guidelines recommend a restrictive red blood cell transfusion strategy based on hemoglobin (Hb) concentrations in critically ill patients. We hypothesized that the arterial-venous oxygen difference (A-V O2diff), a surrogate for the oxygen delivery to consumption ratio, could provide a more personalized approach to identify patients who may benefit from transfusion.
Methods:
A prospective observational study including 177 non-bleeding adult patients with a Hb concentration of 7.0-10.0 g/dL within 72 h after ICU admission. The A-V O2diff, central venous oxygen saturation (ScvO2), and oxygen extraction ratio (O2ER) were noted when a patient's Hb was first within this range. Transfusion decisions were made by the treating physician according to institutional policy. We used the median A-V O2diff value in the study cohort (3.7 mL) to classify the transfusion strategy in each patient as "appropriate" (patient transfused when the A-V O2diff > 3.7 mL or not transfused when the A-V O2diff ≤ 3.7 mL) or "inappropriate" (patient transfused when the A-V O2diff ≤ 3.7 mL or not transfused when the A-V O2diff > 3.7 mL). The primary outcome was 90-day mortality.
Results:
Patients managed with an "appropriate" strategy had lower mortality rates (23/96 [24%] vs. 36/81 [44%]; p = 0.004), and an "appropriate" strategy was independently associated with reduced mortality (hazard ratio [HR] 0.51 [95% CI 0.30-0.89], p = 0.01). There was a trend to less acute kidney injury with the "appropriate" than with the "inappropriate" strategy (13% vs. 26%, p = 0.06), and the Sequential Organ Failure Assessment (SOFA) score decreased more rapidly (p = 0.01). The A-V O2diff, but not the ScvO2, predicted 90-day mortality in transfused (AUROC = 0.656) and non-transfused (AUROC = 0.630) patients with moderate accuracy. Using the ROC curve analysis, the best A-V O2diff cutoffs for predicting mortality were 3.6 mL in transfused and 3.5 mL in non-transfused patients.
Conclusions:
In anemic, non-bleeding critically ill patients, transfusion may be associated with lower 90-day mortality and morbidity in patients with higher A-V O2diff.
Trial Registration:
ClinicalTrials.gov, NCT03767127. Retrospectively registered on 6 December 2018.
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