Factors Influencing Iron Repletion: Failure of One Gram of Intravenous Iron to Adequately Replete Iron Stores

Introduction: Accurately identifying patient-specific factors requiring higher doses of intravenous (IV) iron for repletion can be challenging. Multiple guidelines, including those from the National Comprehensive Cancer Network, recommend parental doses of iron greater than one gram when the iron deficit is in excess. The Ganzoni equation can be used to calculate an iron deficit and appropriate IV iron dose, taking into account the patients weight, hemoglobin, and target hemoglobin. Calculation of the iron deficit has a significant impact on the management of iron deficiency, particularly in clinical settings where precise iron dosing is crucial. We aim to evaluate the ability of the Ganzoni equation to predict iron needs and identify other practical factors to guide decision making surrounding IV iron dosing.

Methods: A retrospective analysis was performed on 400 patients referred to hematology at our academic institution for iron deficiency, or iron deficiency anemia, between 2018-2023 who received at least one dose of IV iron. All doses of iron were 1000mg in total. Data regarding demographics, baseline laboratory values, the etiology of iron deficiency, type and dose of IV iron, and iron deficiency recurrence was collected. Twenty-seven patients who did not replete their iron stores (ferritin <50ng/mL on repeat labs within 28-120 days) were identified. Fifty patients who did replete their iron stores within this time frame were randomly selected as the control group. An iron deficit was calculated using the Ganzoni equation, considering weight at the time of infusion and pre-infusion hemoglobin. A target hemoglobin of 12g/dl for women and 14g/dl for men was used. Unpaired T-tests were used for continuous variables and Fisher's exact test was used for categorical variables.

Results: The median iron deficit calculated using the Ganzoni equation was 846.5mg (95% confidence interval [CI]: 633mg-1026mg) in the non-replete group and 453.8mg (95% CI: 366mg-563mg) in the iron-replete group; p=0.002. Non-replete patients had a median weight of 79.5kg compared to 75.6kg in replete patients, however this was not statistically significant (p=0.288). A ferritin of ≤10ng/mL was present in 22 of 27 non-replete patients and 18 of 50 replete patients with an odds ratio (OR) of 7.822 (95% CI 2.529 to 21.02). The median baseline ferritin was 6ng/mL(95% CI 4-10ng/mL) for non-replete patients and 16ng/mL (95% CI 13-20ng/mL) in replete patients; P<0.001. The median follow-up ferritin for non-replete patients was 26ng/mL and 153ng/mL for replete patients. The median baseline hemoglobin for non-replete patients was 10.6g/dl compared to 12.3g/dl in replete patients; P=0.003. Lower hemoglobin in non-replete patients remains statistically significant when only female patients were analyzed. There were significantly more women with hemoglobin ≤12g/dl in the non-replete group with OR 4.018 (95% CI 1.224-11.12) P=0.0195. When men were analyzed separately, there was no significant difference in hemoglobin between the groups. There was no statistically significant difference between the etiology of iron deficiency or the type of IV iron used. 1000mg IV iron was used in all patients. There was a borderline statistically significant difference in gender, with males more often being non-replete (p=0.0476).

Conclusion: The group that did not replete their iron stores after 1000mg of IV iron had significantly higher iron deficits calculated by the Ganzoni equation. However, the median value remained under 1000mg, thus the equation may underestimate the iron need of these patients. Baseline ferritin levels appear to be a more significant factor in determining which patients will not appropriately respond to one gram of IV iron, particularly at levels ≤10 ng/mL. Additionally, lower baseline hemoglobin levels conferred a higher likelihood of non-repletion, though this was not demonstrated in male patients possibly due to limited sample size. Identifying patients who would benefit from higher doses of intravenous iron upfront is important for expedited symptom resolution. More data is needed in order to predict specific dosages to efficiently replete stores, however factors such as baseline ferritin and hemoglobin can serve to aid in clinical decision making.

No relevant conflicts of interest to declare.