Comment on “Association between non-anemic iron deficiency and outcomes following off-pump coronary artery bypass surgery: a retrospective analysis”
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Dear editor,
We read with interest the study conducted by Shin et al. [1], which reported that preoperative non-anemic iron deficiency was not independently associated with adverse outcomes in patients undergoing off-pump coronary artery bypass grafting (OPCAB). While the authors identified an indirect effect mediated by red blood cell transfusion, we contend that the absence of a direct association may be less a reflection of the biological irrelevance of iron and more a consequence of three key factors: the low-sensitivity surgical model, misaligned diagnostic workflow, and unquantified postoperative iron deficiency
First, the OPCAB model itself may attenuate the detectable impact of iron deficiency. Off-pump techniques are specifically chosen to minimize the profound physiological effects of cardiopulmonary bypass. As noted by the authors, OPCAB “avoids cardiopulmonary bypass-induced hemodilution and coagulopathy” [1]. By design, this creates a low-sensitivity environment in which subtle vulnerabilities, such as impaired mitochondrial energetics or reduced erythropoietic reserves, may not translate into statistically significant adverse events. The relatively low reported transfusion rates in patients with non-anemic iron deficiency compared with those without iron deficiency (25.8% vs. 10.8%) further suggest that this setting buffers the stressors under which iron deficiency would otherwise manifest.
Second, the timing of the iron assessment was not appropriately aligned with any therapeutic opportunity. The median interval between iron testing and surgery was only two days—far shorter than the 4–6 weeks recommended by the perioperative anemia management guidelines [2]. This brief window is physiologically insufficient for a meaningful erythropoietic response even with fast-acting intravenous iron formulations. Thus, the null finding may reflect a process limitation rather than biological futility.
Third, the study did not capture postoperative functional iron deficiency, a phenomenon that is increasingly being recognized after major surgery. Persistent inflammation elevates the levels of hepcidin and acute-phase proteins, promoting iron sequestration within macrophages and reducing bone marrow iron availability [3,4]. This “hidden” deficiency can delay hemoglobin recovery despite adequate total body iron stores. Recent evidence in cardiac surgery further shows that short-term preoperative intravenous iron in iron-deficient non-anemic patients fails to compensate for perioperative iron loss when administered too close to the time of surgery [5].
Taken together, the reported neutral direct association may be a compounded effect of the low-sensitivity model, suboptimal diagnostic timing, and unmeasured postoperative functional iron deficiency. Future prospective studies should incorporate a dynamic iron-deficit index integrating baseline status, estimated intraoperative iron loss, and postoperative inflammatory activity to better represent the true perioperative iron balance and recovery potential. For anesthesiologists, recognizing this hidden postoperative iron restriction may guide more effective timing of perioperative iron assessment and supplementation strategies.
Notes
Funding: None.
Conflicts of Interest: No potential conflict of interest relevant to this article was reported.
Author Contributions: Hsin-An Hsu (Conceptualization; Data curation; Writing – original draft; Writing – review & editing); Wen-Ting Lin (Conceptualization; Data curation; Writing – original draft; Writing – review & editing); Ming-Hui Hung (Conceptualization; Data curation; Supervision; Writing – original draft; Writing – review & editing)