Tag Archives: iron deficiency

AGA Recommendations For Iron Deficiency Anemia

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TG DeLoughery et al. Clin Gastroenterol Hepatol 2024; 22: 1575-1583. Open Access! AGA Clinical Practice Update on Management of Iron Deficiency Anemia: Expert Review

This guideline was developed with adults in mind; however, much of the practice advice is applicable in the pediatric population as well. Here are some of the recommendations:

  • Best Practice Advice 1: No single formulation of oral iron has any advantages over any other. Ferrous sulfate is preferred as the least expensive iron formulation.
  • Best Practice Advice 2: Give oral iron once a day at most. Every-other-day iron dosing may be better tolerated for some patients with similar or equal rates of iron absorption as daily dosing.
  • Best Practice Advice 3: Add vitamin C to oral iron supplementation to improve absorption.
  • Best Practice Advice 4: Intravenous iron should be used if the patient does not tolerate oral iron, ferritin levels do not improve with a trial of oral iron, or the patient has a condition in which oral iron is not likely to be absorbed.
  • Best Practice Advice 5: Intravenous iron formulations that can replace iron deficits with 1 or 2 infusions are preferred over those that require more than 2 infusions.
  • Best Practice Advice 6: All intravenous iron formulations have similar risks; true anaphylaxis is very rare. The vast majority of reactions to intravenous iron are complement activation–related pseudo-allergy (infusion reactions) and should be treated as such.

With regard to iron infusion reactions, the authors note the following:

Being truly allergic to IV iron is very rare—almost all reactions are complement activation–related pseudo-allergy, which are idiosyncratic infusion reactions that can mimic allergic reactions.26 For mild reactions, simply stopping the infusions and restarting 15 minutes later at a slower rate will suffice. For more severe reactions, corticosteroids may be of benefit. Diphenhydramine should be avoided because its side effects of mouth dryness, tachycardia, diaphoresis, somnolence, and hypotension can be mistaken for worsening of the reaction.27 Studies have shown that rates of mild reactions are approximately 1:200 and rates of major reactions are approximately 1:200,000.28

Related information: Our hematologists often recommend Novaferrum (polysaccharide-iron complex) products in children.

Food/diet items with plenty of iron:

  • beef, pork, poultry, and seafood
  • tofu
  • dried beans and peas
  • dried fruits
  • leafy dark green vegetables
  • iron-fortified breakfast cereals, breads, and pastas
  • Use of “lucky fish” (also available at Amazon) while cooking and cooking with cast iron pan can increase iron intake. The lucky fish can be used for 5 years.

Limiting milk consumption can help improve iron absorption.

My take: Iron deficiency anemia is a common issue in pediatric gastroenterology that usually merits evaluation. The AGA practice update provides helpful information with regard to management.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Changing Approach to Iron Deficiency Anemia in Pediatric IBD

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Previously, there have been numerous posts on this blog discussing iron deficiency anemia in pediatric IBD, including an algorithm by CHOP in 2019 (CHOP QI: Anemia in IBD Pathway) and a NASPGHAN position paper in 2020 (Anemia in IBD -NASPGHAN Position Paper). A recent study from Nationwide Children’s highlights ongoing changes in the approach to this common problem.

J Smith et al. JPGN 2023; 76: 313-318. Diagnosis and Treatment of Iron Deficiency and Anemia in Youth With Inflammatory Bowel Disease

This study focused on a quality improvement effort to improve iron deficiency screening in newly-diagnosed patients with IBD. The QI project increased screening from a baseline of 20% to more than 90%. Importantly, this article details a useful algorithm (Figure 4). Key components:

  1. Screen with Ferritin, Iron and TIBC. If Ferritin is less than 30 or iron saturation is less than 20%, it recommends weight-based oral treatment.
  2. If less than 35 kg, options include 3 mg/kg/day (elemental) of ferrous sulfate or Novaferrum. If more than 35 kg, then it recommends ferrous sulfate (325 mg daily=65 mg elemental), ferrous gluconate (325 mg tab bid=36 mg elemental BID), or Novaferrum Ferrex capsule (150 mg daily =150 mg elemental).
  3. Anemia & iron indices are followed every 2-3 months (until improved) and if not resolved, options include either intravenous treatment and/or hematology involvement. For patients less than 50 kg, the authors utilize ferric carboxymaltose (FCM) 15 mg/kg/dose and for those more than 50 kg, FCM at 750 mg dosing.

For IV iron, the authors prefer FCM, which is FDA approved in children 1 yr of age and older, over iron sucrose or iron dextran as the number of infusions needed to replete iron stores is significantly reduced.  FCM is a relatively costly IV iron formulation, but can be given over 15 minutes; however, due to fewer infusions, FCM is likely cost-effective.

In the discussion, the authors caution against relying on laboratory reference values for ferritin and iron saturation which often set lower normative values (eg. Ferritin of 7 and iron saturation of 15%).

My take: This QI project provides a good strategy for dealing with iron deficiency anemia in the pediatric population.

Nationwide Children’s Algorithm

What is the Best Ferritin Threshold and Why It Needs to Be Checked In 1-Year-Olds

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E Mantadakis. J Pediatr 2022; 245: 12-14. (Editorial) Open access. Serum Ferritin Threshold for Iron Deficiency Screening in One-Year-Old Children nutrition.

N Mukhtarova et al. J Pediatr 2022; 245: 217-221. Serum Ferritin Threshold for Iron Deficiency Screening in One-Year-Old Children. This study included 3153 infants, with 698 included in the final analysis.

Key points:

  • 11.4% had iron deficiency, 3.5% had iron deficiency anemia, 8.2% had anemia, and 76.9% were normal.
  • “The authors showed that the hemoglobin threshold of 110 g/L that  is currently recommended for diagnosing anemia at 1-year-old well-child visit corresponds with a very low serum ferritin (4.42 mcg/L).”
  • In a previous study, TARGet Kids!, “a higher serum ferritin was associated with higher cognitive function, with a serum ferritin of 17 mcg/L corresponding with the maximum level of cognition.” That is, iron deficiency, even in the absence of anemia, can contribute to detrimental cognitive outcomes.
  • Thus, current hemoglobin levels and ferritin need to be revised.  Neither a hemoglobin of 11.0 g/dL nor a ferritin of 12 mcg/L is sensitive in detecting iron deficiency in toddlers.
  • In the U.S., only ~40% of anemia in toddlers is attributable to iron deficiency; thus, checking a ferritin can help determine if iron supplementation is worthwhile.

My take: Iron deficiency anemia is a late indicator of iron deficiency and relying on hemoglobin alone could have irreversible detrimental effects on cognitive outcomes. These articles make a strong argument for the following:

  1. Use a ferritin threshold of at least 18 mcg/L to determine if iron deficient
  2. Check a ferritin along with a hemoglobin at 1-year well-child check. 

Related blog post: Briefly Noted: Ferritin Levels and Cognitive Outcomes

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Nutritional Anemia -Expert Review

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At Children’s Healthcare of Atlanta, there has been a long-standing nutritional lecture series coordinated by Kipp Ellsworth.

A recent webinar: Link to WebEx (password PmSU6JPt): Nutrition Support Colloquium featuring Dr. Parmi Suchdev: “The Prevention, Diagnosis, and Treatment of Nutritional Anemia” (30 minute lecture)

Dr. Parmi Suchdev affiliations:

  • Associate Director, Emory Global Health Institute
    Director, Global Health Office of Pediatrics
    Professor of Global Health, Rollins School of Public Health
    Professor of Pediatrics, Emory University School of Medicine
  • BRINDA: BIOMARKERS REFLECTING INFLAMMATION AND NUTRITIONAL DETERMINANTS OF ANEMIA

Here are a few of the slides:

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

Briefly Noted: Ferritin Levels and Cognitive Outcomes

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PC Parkin et al. J Pediatr 2020; 217:189-91.

In this study, the authors conducted a secondary analysis of data from the Optimizing Early Child Development Study (Toronto) with 745 healthy children.  The authors note that the setting is from a high resource area with high maternal education.

Key finding:

  • In pediatric patients, 1-3 years, higher serum ferritin values were associated with higher cognitive function as measured by the Mullen Scales of Early Learning
  • Ferritin of 17 mcg/L or higher corresponded to maximum level of cognition

Based on this study, the authors recommend obtaining a ferritin level at 12 months of age at same time when a hemoglobin is recommended.

My take: The implication of this study is that iron deficiency, even in the absence of socioeconomic status, can have a detrimental effect on cognitive outcomes.

Related blog post: Nutrition Week (Day 6) Iron Deficiency in Breastfed Infants

 

Giant Flag in San Juan, Puerto Rico

Anemia in Pediatric Inflammatory Bowel Disease

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A recent retrospective study (G Aljomah et al. JPGN 2018; 67: 351-5) provides some useful information about anemia in the pediatric inflammatory bowel disease (IBD) population. This study included 153 patients, though the diagnostic tests varied considerably; for example, only 42 patients had a serum transferrin receptor (sTR) assay available at followup.

Key points:

  • 67.3% of patients had anemia at diagnosis.  38.5% had anemia of chronic disease (ACD) and the remainder had either iron deficiency anemia (IDA) or IDA in combination with ACD.
  • 20.5% had anemia at followup approximately 1 year after diagnosis. 5.1% with ACD alone and 15.4% had IDA or IDA in combination with ACD.
  • In a subset of patients with more complete data, it was shown that anemia was much more common in patients with Crohn’s disease: 91.2% at diagnosis and 27.3% at followup compared with patients with ulcerative colitis with 40.0% at diagnosis and 7.7% at followup.

The authors used the sTR index (sTR/log ferritin index) to determine if ACD was present.  “This index can differentiate IDA from ACD; however, it cannot separate IDA from the combination of IDA/ACD.  IDA or IDA/ACD were considered to be present if the sTR index was greater than 1.03. An sTR index of <1.03 was taken to be indicative of the presence of ACD.”

Briefly noted: MR Serpico et al. JPGN 2018; 67: 341-5.  This retrospective study  examined the use of allopurinol to optimize thiopurine levels.  32 of 52 patients remained on the combination for 1 year.  In this group, median alanine transaminase decreased to 19 from 77 (P<0.001) and median 6-TG levels increased to 322 from 166 (P<0.001). In addition, steroid-free remission rates improved to 82% (23 of 28).  About 40% of the initial cohort of 52 patients were switched to antitumor necrosis factor therapy.

My take: The initial study shows that anemia is frequent in pediatric IBD, especially at diagnosis (67%).  Even at followup, 20% of patients had ongoing anemia.

Related blog posts:

Nutrition Week (Day 6) Iron Deficiency Anemia in Breastfed Infants

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In brief: A recent cross-sectional study (KM Clark et al. J Pediatr 2017; 181: 56-61) showed that breastfeeding at 9 months of age in Chinese infants was associated with iron deficiency anemia..  Iron deficiency can contribute to neurodevelopmental delays in addition to anemia.

  • In Zhejiang (n=142), 27.5% of breastfed infants had iron deficiency anemia (IDA) compared with 0% of formula-fed infants.
  • In Hebei (n=813) , 44% of breastfed infants had IDA compared with 2.8% of formula-fed infants.

My take: In later infancy (after 6 months of age), breastfeeding infants are at increased risk for iron deficiency anemia.

screenshot-97

Microcytic Anemia Review

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A useful review of microcytic anemia (NEJM 2014; 371: 1324-31) discusses the most common causes, mechanisms and treatment of microcytic anemia.

Common causes discussed include thalassemia, iron deficiency anemia, and anemia of inflammation.  With the latter, the authors review the pathophysiology: “the cause of this anemia is twofold. First, renal production of erythropoietin is suppressed by inflammatory cytokines, resulting in decreased red-cell production. Second, lack of iron availability for developing red cells can lead to microcytosis.  The lack of iron is largely due to the protein hepcidin, an acute-phase reactant that leads to both reduced iron absorption and reduced release of iron from body stores.”

Treatment of iron deficiency anemia –pointers:

  • Ferrous sulfate (325 mg [65 mg of elemental iron] orally three times a day -considered first line for adults.  Ferrous gluconate at a daily dose of 325 mg [35 mg elemental] is an alternative.
  • “Several trials suggest that lower doses of iron, such as 15 to 20 mg of elemental iron daily can be as effective as higher doses and have fewer side effects.”
  • “There are many oral iron preparations, but no one compound appears to be superior to another.”
  • In those with an inadequate response to oral iron therapy, parenteral iron can be helpful.  The authors note that low-molecular-weight iron dextran (INFeD) is “associated with an incidence of reactions that is similar to that with the newer products but allows for higher doses of iron replacement.”  Typical dosing for adults: 25 mg test dose, and if tolerated for 1 hr, can give 975 mg (1000 mg total) over 4-6 hours.  The low-molecular-weight iron dextran should not be used in patients with previous iron dextran hypersensitivity reactions.
  • Alternative IV iron products: Ferric gluconate [Ferrlecit] 125 mg adult dose over 1 hour -given weekly (8 doses = 1000 mg) or Iron Sucrose [Venofer] 200 mg adult dose over 15-60 min, 300 mg over 1.5 hr, or 500 mg over 4 hr; can repeat in subsequent sessions until total dose of 1000 mg.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Less Red Meat, More Anemia

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The title of this entry is not particularly surprising.  A recent study (JPGN 2013; 57: 722-27) showed that among 263 children (1.5-6 years in age) in Jerusalem, that anemia was present in 11.2%, iron deficiency in 22%, and iron-deficiency anemia in 3.7%.

Key finding:

Children with extremely low red meat consumption had 4-fold higher rates of iron deficiency than those who consumed ≥2 servings per week.  Poultry intake was not protective.

Bottomline: As more families choose a ‘health-conscious diet,’ iron deficiency may become more frequent.

Related blog entry: Help with hepcidin | gutsandgrowth

Inadequate treatment of anemia in IBD

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In some patients with inflammatory bowel disease (IBD), treatment of anemia associated with IBD sometimes results in more symptomatic benefit than treatment of the IBD.  Yet, anemia remains common in IBD, both in children and adults (Inflamm Bowel Dis 2012; 18: 513-19).

Using a cross-sectional observational study design, a tertiary adult and pediatric IBD center reviewed consecutive clinic patients in April 2009.  The prevalence of anemia was 70% (41/59) children, 42% (24/54) adolescents, and 40% (49/124) adult.  In addition, iron deficiency anemia was more common in the pediatric population: 36/41 children and 20/23 adolescents.  In the adults with anemia, only 55% (27/49) were iron deficient.  One of the key determinants of anemia was disease activity.

Interestingly, among patients with iron deficiency, younger age was inversely associated with treatment with iron therapy: 13% of children, 30% of adolescents, and 48% of adults.

Other important aspects of anemia in IBD:

  • Anemic patients can have quality of life scores as poor as those seen in malignancy
  • Almost all IBD patients will respond to either oral or parenteral iron.  Erythropoetin reserved for patients who do not respond to parenteral iron.

Additional references:

  • -NEJM 2005; 352: 1011. Anemia algorithm.  If transferrin saturation <16%, check ferritin.  If ferritin less than 30, then patient with Fe-deficiency; if >100, anemia of chronic disease.  If 30-100, could check soluble transferrin receptor (level of sTranReceptor/log ferritin < 1 is c/w anemia of chronic disease whereas when > 2, c/w combined Fe-def anemia and anemia of chronic disease)
  • -JPGN 2010; 51: 708. 25-50% still anemic 1yr post IBD diagnosis.
  • -IBD 2007; 13: 1545-53. Guidelines for anemia mgt w IBD. Max oral absorption is 10-20mg/day; thus IV iron often needed. Goal for iron Rx is transferrin saturation of 15-50% and ferritin > 30 mcg/L (>100 if active inflammation). Anemia of chronic disease likely if TS <16% and ferritin > 100. Rec IV iron Rx prior to use of Epo. IV iron effective alone in 70-80%. Epo if no response to IV iron & Hgb <10. Consider folic acid & B12 deficiency if high MCV. AZA/6MP usually associated with pancytopenia not isolated anemia.
  • -Gastroenterology 2011; 141: 846. Ferric carboxymaltose better than iron sucrose (Ferrlecit/Venofer) b/c can use higher dose & give more rapidly.