Iron deficiency (ID) and iron deficiency anemia (IDA) are common, underrecognized conditions frequently encountered in the emergency department (ED). Management historically has focused on red blood cell (RBC) transfusion once anemia is detected, despite mounting evidence that transfusion is often unnecessary — and potentially harmful — in hemodynamically stable patients. Intravenous (IV) iron represents a safe, effective, and cost-conscious alternative that treats the underlying pathology rather than temporarily correcting hemoglobin levels.

Iron Deficiency Without Anemia: A Critical Concept

Patients can be iron deficient without anemia. A normal hemoglobin (Hgb) or mean corpuscular volume (MCV) does not rule out ID; it only excludes IDA. IDA is a late manifestation of ID, occurring only after iron stores have been depleted.¹

Iron deficiency alone can cause substantial morbidity. Symptoms include fatigue, irritability, depression, difficulty concentrating, headache, pica (craving for nonfood substances such as clay or paper), pagophagia (ice craving), dyspnea, lightheadedness, exercise intolerance, and restless legs syndrome.¹ Many ED patients presenting with vague or nonspecific complaints may have underlying ID that goes undiagnosed.

Diagnosing Iron Deficiency in the ED

When laboratory evaluation is warranted for patients with nonspecific symptoms, clinicians should consider adding a ferritin level. Ferritin is the only iron study that needs to be ordered in the ED.

A ferritin <30 ng/mL (or µg/L) is diagnostic for ID, regardless of Hgb level. Additional iron studies (serum iron, transferrin saturation, total iron binding capacity (TIBC)) are unnecessary in the ED and rarely change ED management.

Rethinking Transfusion Thresholds

Young, otherwise healthy patients can tolerate Hgb levels as low as 5 g/dL, assuming they are not actively bleeding and have stable vital signs.² Despite this, RBC transfusion remains common in stable patients with IDA. The American Association of Blood Banks (AABB) goes even further and recommends: “Don’t transfuse RBCs for iron deficiency without hemodynamic instability.”³

Blood transfusion should be viewed as a temporary bandage. It increases circulating Hgb but does not treat ID. Iron — administered orally or intravenously — is the definitive therapy.

Limitations of Red Blood Cell Transfusion

RBC transfusions are expensive, represent a limited resource, and expose patients to risks that are both more common and more serious than those associated with IV iron. These include transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), and alloimmunization. Given that transfusion does not correct ID, routine use in stable IDA patients offers limited long-term benefits while increasing costs and patient risk.

Oral Iron: Indications and Limitations

Indications for Oral Iron Therapy

Oral iron remains appropriate for patients with ID without severe anemia, such as those with a ferritin <30 µg/L and a Hgb greater than 9 g/dL, who are clinically stable. In these patients, symptoms of ID should be expected to improve gradually over weeks to months. For patients with chronic medical conditions that may impair absorption, referral for outpatient IV iron should be considered.

Limitations of Oral Iron Therapy

Despite its widespread use, oral iron has important limitations. Gastrointestinal side effects — nausea, constipation, diarrhea, and abdominal pain — are extremely common and lead many patients to discontinue therapy. Even when tolerated, absorption is limited: Patients absorb only approximately 200 mg of elemental iron per month, meaning it takes approximately five months of oral therapy to equal a single 1-gram IV iron dose administered in the ED. Absorption may be minimal or absent in patients with bariatric surgery, celiac disease, or other malabsorptive conditions. Additionally, oral formulations marketed as having fewer side effects often contain lower elemental iron content and may be less effective. In patients with ongoing blood loss (e.g., menorrhagia), oral iron may be insufficient to keep pace with losses.

Evidence-Based Oral Iron Recommendation

When oral iron is chosen, prescribe ferrous sulfate 325 mg once every other day on an empty stomach. Patients should be counseled that treatment requires months to replenish iron stores.

Why IV Iron in the ED?

Safety

IV iron is extremely safe. In one analysis of approximately 36,000 IV iron doses, only two patients required epinephrine for suspected anaphylaxsis.⁴ Another study by Auerbach et al. reported over 20,000 doses of iron dextran with zero serious adverse events.⁵ Mild reactions — myalgias, flushing, and pruritus — occur in about 5 percent of patients and are not true allergies. Assuming stable vital signs, the only contraindications are active infection or known allergy. Notably, the risks of IV iron are lower than those associated with RBC transfusion.

Efficacy and Cost

A recent mini-review demonstrated that IV iron use in IDA can reduce RBC transfusions, decrease hospital readmissions, and improve Hgb by approximately 4 g/dL within one month.⁶ From a cost perspective, RBC transfusion charges (including type and screen) are typically around $2,000, compared with $500 to $1,000 for IV iron dextran.⁷

IV Iron Formulations

There are approximately six IV iron formulations available, differing in dose limits, infusion times, need for test dosing, and cost. All have similar efficacy, so clinicians should work with your hospital’s pharmacy to understand local formulary options. A practical ED approach is to administer 1 gram of IV iron without calculating individualized deficits, simplifying workflow while providing adequate repletion for most patients.

A Practical ED Protocol for IV Iron

One feasible ED protocol uses low-molecular weight iron dextran to deliver a large dose efficiently and at low cost. Inclusion criteria include Hgb ≤9.0 g/dL, ferritin <30 µg/L, hemodynamic stability, and no active infection (recognizing conflicting evidence but erring on the side of caution). The recommended regimen is iron dextran 1,000 mg IV once, infused over 60 minutes with a test dose. Administer a 0.5 mL test dose over 30 seconds. Although evidence supporting test dosing is weak, it remains commonly recommended.⁴ Observe the patient for 15 minutes for anaphylaxis or other serious reactions. Recent evidence suggests this is sufficient compared with the 60 minutes listed in package inserts.⁸ If no reaction occurs, proceed with the full infusion.

A Stepwise Transition Away From Transfusion

For clinicians uncomfortable withholding RBC transfusion, a reasonable transitional strategy is to administer both RBC transfusion and IV iron (before or after RBCs). This allows familiarity with dosing and side effects while still addressing ID. Over time, many clinicians may eliminate RBC transfusion altogether in stable patients.

Conclusion

RBC transfusion is likely overused in stable patients with IDA, exposing patients to unnecessary risk and increasing health care costs. IV iron is safe, effective, and treats the underlying disease. By recognizing ID without anemia, ordering ferritin appropriately, and incorporating IV iron into ED practice, clinicians can move beyond temporary fixes and provide care that is evidence-based, patient-centered, and resource-conscious.

Dr. Lipton is an associate professor of clinical emergency medicine and the program director for the Advanced EM Ultrasonography fellowship at Vanderbilt University Medical Center in Nashville, TN.

References

1. Auerbach M, DeLoughery TG, Tirnauer JS. Iron Deficiency in Adults: A Review. JAMA. 2025;333(20):1813-1823. https://pubmed.ncbi.nlm.nih.gov/40159291/
2. Weiskopf RB, Viele MK, Feiner J, et al. Human Cardiovascular and Metabolic Response to Acute, Severe Isovolemic Anemia. JAMA. 1998;279(3):217-221. https://pubmed.ncbi.nlm.nih.gov/9438742/
3. Five Things Physicians and Patients Should Question. Choosing Wisely. ABIM Foundation. Published April 24, 2014. https://www.aabb.org/docs/default-source/default-document-library/resources/choosing-wisely-five-things-physicians-and-patients-should-question.pdf
4. Arastu AH, Elstrott BK, Martens KL, et al. Analysis of Adverse Events and Intravenous Iron Infusion Formulations in Adults With and Without Prior Infusion Reactions. JAMA Netw Open. 2022;5(3):e224488. https://pubmed.ncbi.nlm.nih.gov/35353168/
5. Auerbach M, Ballard H, Glaspy J. Clinical Update: Intravenous Iron for Anaemia. Lancet. 2007;369(9572):1502-1504. https://pubmed.ncbi.nlm.nih.gov/17482969/
6. Ramos JF, Zeller MP. Evidence-Based Minireview: The role of IV iron in management of patients with iron-deficiency anemia presenting to the emergency department. 2019. Hematology Am Soc Hematol Educ Program. 2019;(1):323-326. https://pubmed.ncbi.nlm.nih.gov/31808876/
7. Jacobs JW, Diaz M, Salazar DEA, et al. United States blood pricing: A cross-sectional analysis of charges and reimbursement at 200 US hospitals. Am J Hematol. 2023; 98(7): E179-E182.https://pubmed.ncbi.nlm.nih.gov/37096559/
8. Kang M, Verstraete, R. Optimizing Iron Dextra Infusion Protocols to Enhance Efficiency and Patient Throughput in an Outpatient Infusion Center: A Process Improvement Initiative. J Hema Oncol Pharmacy. 2025; Vol. 15 Special Feature. Abstract #CR01. https://www.jhoponline.com/issue-archive/2025-issues/march-2025-vol-15-special-feature/optimizing-iron-dextran-infusion-protocols-to-enhance-efficiency-and-patient-throughput-in-an-outpatient-infusion-center