Iron Deficiency Anemia Updates for the Internist

Educational Objectives

The goal of this program is to improve the diagnosis of iron deficiency anemia (IDA). After hearing and assimilating this program, the clinician will be better able to:

1. List the definitive signs or characteristics of IDA.
2. Differentiate among diagnostic tests for IDA.
3. Compare regimens of oral administration of iron in IDA for effectiveness.

Summary

Key takeaways: iron deficiency anemia (IDA) is widespread, particularly among women of childbearing age and older adults with chronic diseases; while testing for IDA is controversial, low ferritin levels <30 ng/mL are a definite sign of IDA; most patients can be treated with oral iron once per day or alternative days depending on the individual, but not 3 times per day; careful management is required to help patients tolerate iron intake as it causes frequent adverse effects

IDA characteristics: include the possibility of heavy bleeding in postmenopausal women; pica (a desire to consume ice) is a sign of IDA; restless legs syndrome (RLS) is a sign of IDA until proven otherwise; while colon cancer is often associated with IDA, IDA can have many causes; most people with IDA do not have cancer; Barton et al (2024) determined the prevalence of iron deficiency by testing 3 definitions, which includes transferrin saturation (TSAT), serum ferritin levels of <15 ng/mL, and <25 ng/mL among women; it revealed that the prevalence of iron deficiency is common, especially among women of childbearing age (25-54 yr) and >25% in Hispanic women; iron deficiency or IDA in pregnant women can affect pregnancy outcomes, eg, neurocognitive development of the babies, preterm labor, premature babies; IDA identified in pregnant women should be treated with intravenous (IV) iron

Screening for IDA: the American Academy of Pediatric guidelines recommend screening for iron deficiency in children due to its impact on neurocognitive development; there are no screening recommendations for iron deficiency in people of childbearing age or in the general population, and no universal definition exists for it; the prevalence of iron deficiency varies depending on the definition, but in some populations, eg, people who have early onset of menstruation, high rates of obesity, or socioeconomic factors affecting their diet, iron deficiency could be ≤30% in women of reproductive age; most current knowledge about the clinical effects of iron deficiency focuses on anemia, yet only 20% of patients with iron deficiency have anemia; the health effects of iron deficiency in the remaining 80% of patients without anemia are less clear; many studies have focused on the diagnosis of cancer in patients with IDA rather than screening; the American Gastroenterological Association recommends investigating every patient with IDA or iron deficiency, but this approach presents practical challenges

Risk factors (RFs) of IDA: obstetric causes include delivering babies and heavy bleeding or regular menstruation, which is the most common RF; it is unclear if cancer is a RF, and ≈2% of IDA cases are attributed to cancer; other common RFs in the primary care population include people with unusual blood types, universal donors, and other blood donors; an unbalanced diet can lead to IDA; changes in dietary patterns and increased reliance on fast food have decreased the amount of iron in the diet; hence, it is challenging to replete iron deficiency through diet alone; RFs vary by population, eg, in US population, gastric bypass surgery is the most common RF, as it impairs iron absorption and necessitates lifelong iron supplementation; symptoms of pica and RLS (≈30%) are linked to iron deficiency; RLS specialists recommend a ferritin level of 75 ng/mL as an effective therapy target; some early retrospective studies suggested that proton pump inhibitors cause iron deficiency, but these studies were based on poor data

Diagnosis of IDA: the diagnosis of IDA is complex; low serum ferritin levels and low iron saturation are reliable indicators of IDA; when serum ferritin levels are not low, a low TSAT is a reliable indicator of IDA; however, if the patient is on iron supplements, the TSAT may falsely show high levels of iron; to diagnose and treat iron deficiency, anemia is not required, but its presence indicates classical findings; the soluble transferrin receptor (sTfr) is one of the more commonly referred tests in the literature that is relatively newer, not widely available, and expensive; sTfr is not routinely recommended but can be helpful in determining if IDA is associated with anemia of chronic disease, complex medical conditions, or other conditions; a bone marrow biopsy is the gold standard diagnosis for IDA

The Kidney Disease Improving Global Outcomes guidelines: recommend different ferritin thresholds for patients with chronic kidney disease (CKD), who also have a functional iron deficiency because of underlying renal disease; so, do not treat these patients first with stimulating agents before they receive iron replenishment (IV iron and ferritin thresholds); to treat patients with CKD not on dialysis and patients on dialysis, CKD 100 ng/mL and <200 ng/mL ferritin are sufficient, respectively; in malnutrition, iron deficiency increases susceptibility to lead poisoning as iron deficiency leads to more lead absorption; a condition with stable ferritin levels and low mean corpuscular volume is thalassemia; 97% of patients with IDA have low ferritin levels 2 to 3 days after transfusion, so iron levels can be tested

Treatment of IDA: oral iron is widely available, effective, inexpensive, and administered once per day; in the past, it was prescribed thrice a day, but this led to poor patient tolerance, constipation, and stomach upset, resulting in poor adherence; per observation, iron supplements given every other day yielded similar results compared with 3 times a day; new study comparing once a day administration with every other day showed replacement was faster with once a day administration vs every other day, but every other day also proved effective; however, the choice of dosing depends on the patient’s preference, as achieving patient adherence can be difficult; there are many over-the-counter formulations available, but there is no strong evidence that one is superior to the others; avoid sustained-release or coated preparations because of absorption issues; do not take iron with calcium, as calcium impairs iron absorption; taking iron on an empty stomach in the morning, ideally with vitamin C (orange juice), is the best choice; it is recommended to start with liquid formulations first, as they are commonly available and can be titrated up gradually to the patient’s tolerance level; be cautious of iron overdose in children, as it is the leading cause of medication overdose in this age group; iron supplements are typically used for ≈8 wk on alternate days until retest; an increase in iron levels is not seen immediately, especially for IDA, as it takes several weeks

IV iron: currently, people use IV iron more frequently because it does not cause anaphylaxis, unlike older formulations; there are many available formulations, some of which are expensive, especially iron dextran (single dose); the choice of formulation depends on community preferences, availability, and insurance coverage; IV iron is recommended for older patients who cannot tolerate oral iron, who are severely symptomatic, or who require rapid repletion; it is commonly used in older patients undergoing chemotherapy or in cases of impaired absorption; data show that, regardless of the iron formulation, patients tolerance and adherence are important; oral iron may suffice for the short term without the need for IV supplementation; during laboratory retests, aim for ferritin levels ≥50 ng/mL, especially for patients with RLS

Screening: the AGA recommends endoscopy for all patients, while obstetrics highlights that 30% of women experiencing bleeding have iron deficiency, and not all of them require a colonoscopy; the speaker advises that screening decisions should rely on patient history and professional judgment; routine screening is generally not recommended for most patients

Readings

Barton JC, Wiener HW, Barton JC, et al. Prevalence of iron deficiency using 3 definitions among women in the US and Canada. JAMA Netw Open. 2024;7(6):e2413967. doi:10.1001/jamanetworkopen.2024.13967; Bhuiyan MN, Giti S, Akhter M, et al. The role of soluble transferrin receptor in diagnostic work up for the assessment of iron status and iron deficiency. Haematol J Bangladesh. 2022;6(2):54-60. doi:10.37545/haematoljbd202294; Imai R, Higuchi T, Morimoto M, et al. Iron deficiency anemia due to the long-term use of a proton pump inhibitor. Intern Med. 2018;57(6):899-901. doi:10.2169/internalmedicine.9554-17; Johnson-Wimbley TD, Graham DY. Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol. 2011;4(3):177-184. doi:10.1177/1756283X11398736; Mackie S, Winkelman JW. Normal ferritin in a patient with iron deficiency and RLS. J Clin Sleep Med. 2013;9(5):511-513. doi:10.5664/jcsm.2680; Pasupathy E, Kandasamy R, Thomas K, et al. Alternate day versus daily oral iron for treatment of iron deficiency anemia: a randomized controlled trial [published correction appears in Sci Rep. 2023;13(1):10711. doi: 10.1038/s41598-023-37878-4]. Sci Rep. 2023;13(1):1818. doi:10.1038/s41598-023-29034-9.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Watts was recorded at the 40th Annual Internal Medicine Update, held July 26-28, 2024, on Mackinac Island, MI, and presented by the University of Michigan School of Medicine. For information about upcoming CME activities from this presenter, please visit https://ww2.highmarksce.com/micme. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

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The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Lecture ID:

IM720401

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.