Iron deficiency anemia in patients with inflammatory bowel disease

Figures & data

Table 1 Common causes of iron deficiency anemia^3–5

Common causes of iron deficiency anemia
Increased iron loss	GI tract ulcers Inflammatory bowel disease – Ulcerative colitis – Crohn’s disease GI malignancy Gastritis (particularly due to Helicobacter pylori) Colonic or gastric polyps Postoperative patients with significant blood loss Intestinal parasites Angiodysplasia (arteriovenous malformations) Aspirin/nonsteroidal anti-inflammatory drug use Regular blood donors Diverticular bleeding Potassium tablets
Decreased iron absorption (malabsorption)	Upper GI pathology – Celiac disease – Crohn’s disease – Chronic gastritis – Gastric lymphoma Gastrectomy Intestinal bypass Duodenal pathology Achlorhydria Giardiasis Short bowel syndrome Gastrojejunostomy Bacterial overgrowth Helicobacter pylori colonization Drugs that bind iron Drugs that decrease gastric acidity Chronic renal failure
Increased demand for iron	Growing infants and children Adolescence Menstruation Lactation Pregnancy Erythropoietin therapy
Decreased iron intake	Diet (lack of balanced diet, vegetarians, vegans) Low socioeconomic status Alcoholism Elderly

Abbreviation: GI, gastrointestinal.

Table 2 Diagnostic tests for iron deficiency anemia^{12,15–17,59,60}

Test	Applicability
Complete blood count	Suggestive of iron deficiency Not the diagnostic test of choice for iron deficiency Hemoglobin, g/dL (to assess severity of anemia) ○ <13 – men ○ <12 – women
Serum ferritin	Diagnostic test of choice Adult levels, μg/L ○ <15 – diagnostic of iron deficiency ○ 15–50 – probable iron deficiency ○ 50–100 – possible iron deficiencya ○ >100 – iron deficiency unlikely ○ Persistently >1000 – consider test for iron overload
Other
Serum iron Iron-binding capacity Transferrin saturation	Low serum iron and high iron-binding capacity and transferrin saturation <16% may aid in the diagnosis of iron deficiency

Note:

a Serum ferritin levels of 50–100 μg/L may be indicative of iron deficiency in IBD.

Abbreviation: IBD, inflammatory bowel disease.

Table 3 Differential diagnosis of iron deficiency anemia, anemia of chronic disease, and anemia of mixed origin

	Iron deficiency anemia	Anemia of chronic disease	Anemia of mixed origin
Serum ferritina	Decreased	Normal or increased	Normal
Serum iron	Decreased	Decreased	Decreased
Transferrin	Increased	Decreased or normal	Decreased
Transferrin saturation	Decreased	Decreased	Decreased
Mean corpuscular volume	Decreased	Decreased or normal	Decreased or normal
Hemoglobin	Decreased	Decreased	Decreased
Iron-binding capacity	Increased	Decreased	Decreased to low normal
Serum transferrin receptor	Increased	Normal	Increased or normal
Serum transferrin receptor index	High (>2)	Low (<1)	High (>2)
C-reactive protein	Normal	Increased	Increased
Erythropoietin	Increased	Normal or slightly increased	Increased or normal
Cytokine levels	Normal	Increased	Increased

Notes:

a The normal range of ferritin values is between 30–100 μg/L. Copyright © 2009, World Journal of Gastroenterology. Adapted with permission from [Bermejo F, García- López S. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J Gastroenterol. 2009;15(37):4638–4643].⁴ Adapted by permission from Macmillan Publishers Ltd: [Nature Reviews Gastroenterology and Hepatology]. Stein J, Hartmann F, Dignass AU. Diagnosis and management of iron deficiency anemia in patients with IBD. Nat Rev Gastroenterol Hepatol. 2010;7(11):599–610. Copyright 2010.⁷

Figure 1 Algorithm for the management of iron deficiency anemia in patients with IBD and other GI diseases.

Adapted by permission from Macmillan Publishers Ltd: [Nature Reviews Gastroenterology and Hepatology]. Stein J, Hartmann F, Dignass AU. Diagnosis and management of iron deficiency anemia in patients with IBD. Nat Rev Gastroenterol Hepatol. 2010;7(11):599-610, Copyright 2010.⁷

Notes:^aHigher levels of serum ferritin do not exclude the possibility of iron deficiency. Serum ferritin <100 μg/L may still be consistent with iron deficiency in patients with IBD;^15bonly iron dextrans have a broad indication for the treatment of iron deficiency anemia.
Abbreviations: Hb, hemoglobin; MCV, mean corpuscular volume; MCHC, mean corpuscular hemoglobin concentration; RDW, red cell distribution width; IBD, irritable bowel disease; CHF, congestive heart failure; GI, gastrointestinal; IV, intravenous; ESA, erythropoiesis-stimulating agent.

Table 4 Comparison of oral iron preparations available in the United States

Oral iron preparation	Brand name(s)	Recommended dose	Elemental iron (mg)
Ferrous sulfate	Feosol^®, Fer-Gen-Sol^®, Fer-in-Sol^®, Fer-Iron	325 mg three times/day	65
Ferrous gluconate	Fergon^®	325 mg three times/day	38
Ferrous fumarate	Femiron, Ferretts, Ferro-Sequels^®, Nephro-Fer^®	324 mg three times/day	106

Note: Adapted by permission from Macmillan Publishers Ltd: [American Journal of Gastroenterology]. Rizvi S, Schoen RE. Supplementation with oral vs intravenous iron for anemia with IBD or gastrointestinal bleeding: is oral iron getting a bad rap? Am J Gastroenterol. 2011;106(11):1872–1879. Copyright 2011.⁶¹

Table 5 Comparison of intravenous iron preparations available in the United States^7,38–42

	LMWD	HMWD	Iron sucrose	Ferric gluconate	Ferumoxytol
Brand name	INFed^®	DexFerrum^®	Venofer^®	Ferrlecit^®	Feraheme^®
Molecular weight (kD)	73	165	43.3	37.5	731
Labeled indication	Iron deficiency anemiaa	Iron deficiency anemiaa	Iron deficiency anemia in patients with CKD	Iron deficiency anemia in adults and children aged ≥6 years with CKD and receiving dialysis and supplemental epoetin	Iron deficiency anemia in adults with CKD
Dosing and administration
Test dose required	Yes Initial test dose of 0.5 mL required	Yes Initial test dose of 0.5 mL required	No	No	No
Adult recommended dose	According to LBW and observed Hb concentration: dose (mL) = 0.0442 (desired Hb − observed Hb) × LBW + (0.26 × LBW) eg, 70 kg adult with Hb range of 3–10 g/dL will require 55–33 mLb	According to LBW and observed Hb concentration: dose (mL) = 0.0442 (desired Hb − observed Hb) × LBW + (0.26 × LBW) eg, 70 kg adult with Hb range of 3–10 g/dL will require 55–33 mL	HDD-CKD: 100 mg slow IV injection (2–5 min) or infusion of 100 mg in max 100 mL normal saline over 15 min at each dialysis session for a total cumulative dose of 1000 mg NDD-CKD: 200 mg slow IV injection (2–5 min) on five separate occasions over 14 days for a total cumulative dose of 1000 mg PDD-CKD: total cumulative dose of 1000 mg by slow infusion in three divided doses over 28 days	125 mg in 10 mL diluted in 100 mL normal saline for IV infusion over 1 hour. Most pts will require a cumulative dose of 1000 mg delivered over eight sessions at sequential dialysis treatments	510 mg followed by a second 510 mg dose 3–8 days later administered undiluted as IV injection up to 1 mL/sec
Dosage adjustments	None	None	None	Lower doses may be required in elderly patients	None

Note:

a Only LMWD and HMWD have a broad indication for the treatment of iron deficiency anemia;

b anecdotally, total doses of 1 to 1.5 g LMWD are commonly used in clinical practice.

Abbreviations: LMWD, low molecular weight dextran; HMWD, high molecular weight dextran; CKD, chronic kidney disease; LBW, lean body weight; Hb, hemoglobin; HDD-CKD, hemodialysis dependent-chronic kidney disease; IV, intravenous; NDD-CKD, nondialysis dependent-chronic kidney disease; PDD-CKD, peritoneal dialysis-chronic kidney disease.

Table 6 Indications for IV iron therapy^3,15

Indications for IV iron therapy in patients with GI disease Severe anemia (hemoglobin value <10 g/dL) Patients with symptoms such as dyspnea on mild exertion, tachycardia, severe fatigue, and ongoing gross blood loss from the GI tract, irrespective of hemoglobin level Patients in need of quick recovery Intolerance to oral iron therapy Failure of oral iron therapy Severe intestinal disease activity Concomitant erythropoietic therapy Patient preference

When to consider using IV iron as first-line therapy Inflammatory bowel disease Situations that require a rapid correction of anemia, such as those requiring an elective procedure in a few weeks (ie, preoperative) Congestive heart failure Upper GI bleeding (replete iron with IV not oral; practical issue of black stools from oral iron)

Abbreviations: IV, intravenous; GI, gastrointestinal.

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