Reticulocyte hemoglobin content: a new frontier in iron deficiency diagnostics for major surgical patients.

Background: Iron deficiency (ID) is the most common nutritional deficiency among patients undergoing major surgery. Treatment of ID is straightforward, however implementing a comprehensive anemia management strategy within clinical routines is complex. Recently, reticulocyte hemoglobin content (Ret-He) has been evaluated as an early marker for ID diagnosis.

Method: In this retrospective study, 2,966 major surgical patients from two University Hospitals were screened for the presence of ID and the significance of Ret-He in diagnosis ID was evaluated in both non-anemic and anemic patients. According to hemoglobin, ferritin, and transferrin saturation concentrations patients were assigned to a Control group (no anemia, no ID), ID group (no anemia, ID), IDA group (anemia, ID) or Others group (anemia, no ID).

Results: In total, 2,760 patients were included in analysis: Control (n = 1500; 54.2%), IDA (n = 412; 14.9%), ID (n = 487; 17.6%), and Others (n = 370; 13.4%). Ret-He was significantly decreased in the IDA group compared to ID, Control and Others, respectively (p < 0.001). The ROC curve analysis revealed an AUC of 0.842 (95% CI (0.82-0.87)) at Ret-He cutoff 33.5 pg, by which IDA was discriminated with 69.7% (95% CI (65.3-74.0%)) sensitivity and 85.7% (95% CI (82.3-86.1%)) specificity. Of the 370 patients with anemia of unknown cause (Others group) 131 had Ret-He levels < 33.5 pg. In these patients, the median values for ferritin was 492.0 ng/ml (333.5; 818.5 ng/ml) and transferrin saturation 11.9% (18.0; 23.3%). Logistic regression identified significant predictors of ID, with each decrease in Hb and Ret-He associated with a 19.4% (OR = 0.806; p < 0.001) and 26% (OR = 0.740; p < 0.001) increase in the odds of ID, respectively.

Conclusion: This study highlights the potential of Ret-He as a promising alternative marker for diagnosing ID in patients undergoing major surgery, particularly in cases of elevated ferritin levels or non-anemic patients. Ret-He may serve as a valuable tool to prioritize patients for further iron status testing, especially when preoperative time is limited.