In reply: Erythropoietin and iron: separating the builder from his blocks
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CORRESPONDENCE
In reply: Erythropoietin and iron: separating the builder from his blocks Nikhil Mistry, MSc . Tiffanie Kei, MSc . Katerina Pavenski, MD, FRCPC . C. David Mazer, MD, FRCPC . Gregory M. T. Hare, MD, PhD, FRCPC
Received: 1 October 2019 / Revised: 1 October 2019 / Accepted: 3 October 2019 Ó Canadian Anesthesiologists’ Society 2019
To the Editor, We appreciate the opportunity to respond to the insightful comments by Abeysiri et al.1 We agree that the hormone erythropoietin (EPO) can be considered the ‘‘builder of red blood cells (RBCs)’’ and that ‘‘iron is a substrate for hemoglobin’’ which provides the foundation for the oxygen-carrying capacity of the RBC. Thus, the active hormone or ‘‘builder’’ acts together with the iron ‘‘building blocks’’ to produce optimal erythropoiesis and minimize RBC transfusion in the setting of acute surgical blood loss. Although we did not comment on iron status in our initial analysis, this information is important to the reported findings. Upon re-review of the manuscripts included in our review, 19 of the 25 (76%) reported iron status, with six of the 19 (32%) showing evidence of iron deficiency (i.e., low ferritin and/or transferrin saturation) (eTable, available as Electronic Supplementary Material). Interestingly, iron deficiency was an exclusion criterion in seven of the 25 (28%) studies, indicating that the purpose of therapy was not to treat iron deficiency, but rather to optimize blood management. Abeysiri et al. correctly point out that inclusion of studies that assess the impact of iron therapy in patients without iron deficiency may provide a source of confounding.1 Many of the studies Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12630-019-01510-9) contains supplementary material, which is available to authorized users. N. Mistry, MSc T. Kei, MSc K. Pavenski, MD, FRCPC C. D. Mazer, MD, FRCPC G. M. T. Hare, MD, PhD, FRCPC (&) St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada e-mail: [email protected]
included patients that were not iron deficient; in these patients, iron therapy would not likely impact erythropoiesis or RBC transfusion. By contrast the addition of exogenous EPO would be expected to boost erythropoiesis, above physiologic levels, and have higher likelihood of impacting RBC transfusion avoidance. Indeed, this was one of the important findings of our systematic review—i.e., exogenous EPO plus iron vs iron alone augmented erythropoiesis (elevated reticulocyte count 170% vs 1% increase), increased postoperative hemoglobin (increased by 9.0 gL-1; 95% confidence interval [CI], 6.6 to 11.4), and reduced the incidence of RBC transfusion (relative risk 0.57; 95% CI, 0.46 to 0.71).2 This may inform the optimal treatment of the surprisingly large proportion of patients (approximately 30%) who are anemic prior to undergoing elective surgery.3 Many of these patients are iron deficient, and therefore may benefit from iron alone. In this setting, the endogenous EPO ‘‘builder’
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