Richard Godby, MD 

ASH Clinical Practice Guidelines in Development and Remaining Evidence Gaps in IDA Management 

An expert reviews the scope and methodology of the ASH clinical practice guidelines on iron deficiency anemia currently in development, identifies the most significant remaining evidence gaps, and summarizes the practical takeaways for clinicians managing IDA today.

The American Society of Hematology is developing its first clinical practice guidelines specifically addressing iron deficiency anemia — a notable undertaking given how common the condition is and how much variation currently exists in diagnostic and management practices. The guidelines will address at least 10 clinical questions prioritized for their potential impact on practice, including diagnostic thresholds across populations such as children, pregnant women, and patients with inflammatory conditions; optimal oral iron dosing and formulation selection; IV iron use in specific populations; and preoperative anemia management. The panel includes more than 20 members — hematologists, pediatric hematologists, patient representatives, implementation science experts, and international members — and is applying GRADE methodology with systematic reviews. The guidelines are targeted for publication in Blood Advances.

The most consequential evidence gaps the ASH guidelines are designed to address reflect longstanding uncertainties that clinicians encounter daily. Optimal oral iron formulation and dosing schedules are not definitively established, though alternate-day dosing has gained traction as a tolerability strategy with comparable absorption. Head-to-head comparisons of IV iron formulations in specific populations — including those with IBD — remain limited, leaving formulation choice largely driven by practical and logistical factors rather than population-specific efficacy data. Management of IDA in pediatric and pregnant populations is currently extrapolated from adult data, and the ASH guidelines specifically plan to address these populations with dedicated evidence synthesis rather than continued extrapolation.

In this final segment of the video discussion on IDA management, Richard Godby, MD, synthesizes the practical bottom line for clinicians managing IDA in the current evidence environment. Ferrous sulfate once daily remains the appropriate starting point for most patients, with escalation to IV iron indicated when oral therapy fails, is not absorbed, or is not tolerated. IV iron formulation should be selected based on practical considerations — primarily the number of infusions required — given that all available products are considered safe and similarly efficacious. Godby closes with an emphasis that cutting across every clinical scenario discussed: iron repletion is necessary but not sufficient, and clinicians must maintain focus on identifying and managing the underlying source of iron deficiency to prevent recurrence and achieve durable benefit for their patients.

Videos

Learn when IV iron beats pills and when endoscopy matters in GI-related anemia—from bariatric surgery to IBD, celiac, GAVE, angiectasias.

Special Populations — IDA After Bariatric Surgery, in IBD, Portal Hypertensive Gastropathy, GAVE, Celiac Disease, and Small Bowel Angioectasia 

An expert reviews the management of iron deficiency anemia across 6 distinct clinical populations, addressing the factors that drive iron deficiency in each setting and the evidence guiding route of iron repletion and adjunctive therapy.

Iron deficiency anemia is prevalent across a range of clinical populations in which the etiology, severity, and preferred management approach differ substantially from the general adult presentation. Following bariatric surgery, IDA is common and largely attributable to disruption of duodenal iron absorption; IV iron is preferred for severe cases or when oral supplementation is ineffective, and it is generally better tolerated in this population than oral formulations. Importantly, all post-bariatric patients who develop IDA should undergo esophagogastroduodenoscopy (EGD) to exclude anastomotic ulceration as a contributing source of blood loss. In inflammatory bowel disease (IBD), IDA affects up to 90% of patients and is multifactorial — driven by gastrointestinal blood loss, impaired absorption, and inadequate intake — and the first step is determining which of these mechanisms is dominant. IV iron is generally superior to oral iron in IBD, and the European Crohn's and Colitis Organization recommends IV iron as first-line therapy when hemoglobin is below 10 g/dL. Active inflammation contributing to blood loss should be addressed concurrently.

Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) represent 2 additional conditions where IDA management must be integrated with treatment of the underlying cause. In portal hypertensive gastropathy, oral iron can be initiated as there is no malabsorptive defect, and beta-blockers to reduce portal hypertension should be considered as part of the broader management plan. For GAVE, the mainstay of therapy is endoscopic treatment to reduce bleeding, with iron repletion — oral or IV depending on severity and oral tolerance — provided to all affected patients. In celiac disease, iron deficiency and IDA are common and frequently improve with strict adherence to a gluten-free diet; however, up to 20% of patients may remain iron deficient despite dietary compliance, and oral iron is indicated based on symptom severity, with IV iron considered when oral therapy produces an inadequate response.

In this segment of the video discussion on IDA management, Richard Godby, MD, addresses small bowel angioectasia as a particularly challenging population given re-bleeding rates of 30% to 50%, which sustain a cycle of recurrent iron deficiency and anemia. Endoscopic therapy remains the primary intervention when technically feasible, and adjunctive agents — including somatostatin analogs and antiangiogenic therapy such as thalidomide — can be considered alongside endoscopic management to reduce recurrent bleeding. Godby frames the management of IDA across all of these populations with a consistent principle: identifying and addressing the underlying cause of iron deficiency is not secondary to iron repletion but must occur in parallel, as repletion alone without source control will produce temporary benefit at best and fail to prevent recurrence.

Learn when IV iron beats pills for anemia after bariatric surgery, IBD, celiac, GAVE and angiectasias—plus key endoscopy steps.

Intravenous Iron — When to Escalate, Formulation Choice, and Safety Considerations 

An expert discusses the clinical thresholds for transitioning from oral to intravenous iron, the practical considerations that guide formulation selection among available IV iron products, and the safety profile of IV iron including the distinction between true anaphylaxis and complement activation-related reactions.

Intravenous (IV) iron is indicated when oral iron is ineffective, not tolerated, or not feasible given the patient's underlying condition. A practical benchmark for assessing oral iron response is a hemoglobin increase of approximately 1 g/dL within the first 2 weeks of therapy and a rise in ferritin within the first month. Failure to meet these benchmarks, patient-reported intolerance, or a clinical situation in which iron losses are known to exceed the capacity of oral absorption — such as post-bariatric surgery, active inflammatory bowel disease, or other malabsorptive states — all constitute grounds for escalating to IV iron. Many clinical teams also initiate IV iron empirically in high-risk patients rather than waiting for a demonstrated oral iron failure, recognizing that the trial of oral therapy in these populations is unlikely to succeed and delays repletion.

All currently available IV iron formulations have similar efficacy and overall safety profiles, and no single product is preferred on safety grounds alone. In practice, formulation selection is often driven by the number of infusions required to achieve full iron repletion — products such as ferric carboxymaltose, ferric derisomaltose, ferumoxytol, and low-molecular-weight iron dextran can each replace iron stores in 1 to 2 infusions, which is a meaningful advantage for patient convenience. True anaphylaxis to IV iron is rare; the majority of reactions encountered in practice are complement activation-related pseudoallergy (CARPA) reactions, managed by pausing the infusion, allowing the reaction to self-resolve, and resuming at a slower rate. These reactions occur in approximately 1 in 200 infusions; more severe CARPA reactions occur in approximately 1 in 200,000 infusions. Diphenhydramine premedication should be avoided, as its side effects can mimic infusion reactions and complicate clinical assessment.

In this segment of the video discussion on IDA management, Richard Godby, MD, highlights 2 product-specific considerations that clinicians and infusion teams should be aware of. Ferumoxytol has historically been used as an MRI contrast agent, and if a patient receiving ferumoxytol will undergo MRI imaging within 3 months, the radiology team should be notified to avoid interpretive interference. Ferric carboxymaltose, particularly with repeated infusions, carries a higher tendency to cause hypophosphatemia — a side effect that warrants monitoring and patient awareness. Godby frames these not as reasons to avoid these formulations but as practical considerations that should be part of the clinical team's and patient's shared understanding before infusion is initiated.

Learn when to switch to IV iron, which formulations need fewer infusions, and how to manage rare reactions, MRI issues, and hypophosphatemia.

Oral Iron — Formulation Selection, Dosing Frequency, and Absorption Optimization

An expert reviews the evidence on oral iron formulation choice, the impact of dosing frequency on tolerability and absorption, and practical steps clinicians can recommend to patients to maximize oral iron uptake.

No single oral iron formulation has demonstrated clear advantages over others in terms of efficacy or tolerability, though ferrous sulfate remains the least expensive option and is a practical first choice for most patients. Gastrointestinal side effects are common with oral iron therapy, with up to 10% of patients experiencing constipation, diarrhea, or nausea — a frequency that meaningfully affects adherence and is an important consideration when counseling patients at the time of initiation. Formulation selection in practice is therefore often guided as much by cost and side effect profile as by any differential evidence of superiority among available products.

Dosing frequency is an area where the evidence has meaningfully clarified practice in recent years. Oral iron should be given at most once daily — more frequent dosing does not improve outcomes and increases the risk of side effects. The mechanism underlying this recommendation involves hepcidin: oral iron ingestion raises endogenous hepcidin levels, which can remain elevated for up to 48 hours and suppress intestinal iron absorption during that window. Every-other-day dosing exploits this biology, improving tolerability while maintaining absorption rates comparable to daily dosing. The data supporting alternate-day dosing are promising, and further studies are underway to better define its role across patient populations.

In this segment of the video discussion on IDA management, Richard Godby, MD, addresses the practical questions clinicians most commonly face when initiating oral iron therapy. He notes that while the evidence for vitamin C supplementation as an absorption enhancer — through its role in preventing insoluble iron compound formation and reducing ferric to ferrous iron— is mixed, the evidence against tea and coffee is clear and consistent: both are potent inhibitors of iron absorption and should be avoided within 1 hour of taking an oral iron supplement. Godby advises that oral iron is best absorbed on an empty stomach but can be taken with food when gastrointestinal intolerance is limiting adherence, framing tolerability as a practical priority since a regimen the patient can sustain is more valuable than an optimal one they cannot.

Learn smarter oral iron dosing: once daily or every other day to cut GI side effects, boost absorption, and avoid tea/coffee.

Richard Godby, MD

Articles