Iron deficiency anemia (IDA)

 A 35-year-old woman presents with a 6-month history of fatigue, generalized weakness, and shortness of breath on exertion. She reports pica, specifically craving and eating ice. She follows a vegetarian diet and has chronic painless bright red rectal bleeding, with blood on the toilet paper and surface of the stool. She also reports chronic constipation with straining, anal itching, and discomfort. Examination shows pallor of the skin and conjunctiva, with no lymphadenopathy or hepatosplenomegaly. External hemorrhoids are noted on anorectal examination. Laboratory studies show low hemoglobin with a low MCV. Iron studies demonstrate low ferritin, low serum iron, high TIBC, and low transferrin saturation. Diagnosis?

The diagnosis is iron deficiency anemia, likely related to chronic blood loss. The external hemorrhoids may explain the anal itching and discomfort, but they should not be assumed to be the source of the painless rectal bleeding without further anorectal and gastrointestinal evaluation.

1. Definition

Iron deficiency anemia (IDA) is an anemia caused by insufficient iron availability for hemoglobin synthesis, typically producing microcytic, hypochromic red blood cells when deficiency becomes established.

2. Etiology

1.      Chronic blood loss

o    Gastrointestinal bleeding

o    Menstrual blood loss

o    Other chronic bleeding sources

2.      Reduced dietary iron intake

o    Vegetarian diets predominantly provide non-heme iron, which has lower bioavailability than heme iron

o    Vegetarianism itself does not cause IDA, but inadequate iron intake may contribute, particularly when combined with chronic blood loss

3.      Increased iron requirements

o    Pregnancy

o    Growth

4.      Reduced iron absorption

o    Celiac disease

o    Atrophic gastritis

o    Bariatric or gastric surgery

o    Other malabsorptive disorders

3. Pathophysiology

1.      Progressive iron loss or inadequate absorption causes depletion of iron stores

2.      Reduced available iron impairs heme synthesis

3.      Hemoglobin production decreases

4.      Erythrocytes become progressively microcytic and hypochromic

5.      Iron is absorbed predominantly in the duodenum and proximal small intestine

4. Clinical Features

1.      Fatigue and generalized weakness

2.      Dyspnea on exertion

3.      Pallor

4.      Pica

o    Pagophagia, or craving for ice, is particularly associated with iron deficiency

5.      Reduced exercise tolerance

6.      Koilonychia in longstanding deficiency

7.      Glossitis and angular cheilitis may occur

8.      Severe anemia may cause palpitations, tachycardia, or cardiovascular strain

Associated condition:

1.      Plummer-Vinson syndrome

o    Iron deficiency anemia

o    Esophageal webs

o    Dysphagia

5. Diagnosis

5.1 Complete Blood Count

1.      Low hemoglobin

2.      Low MCV, typically <80 fL

3.      Increased RDW is common

4.      Peripheral smear may show microcytosis, hypochromia, and anisopoikilocytosis

5.      Reactive thrombocytosis may occur

5.2 Iron Studies

Typical findings include:

1.      Low serum ferritin

o    Most useful marker of depleted iron stores

o    In patients with anemia, ferritin <45 ng/mL supports iron deficiency

o    Ferritin may be falsely normal or elevated during inflammation

2.      Low serum iron

3.      Increased TIBC or transferrin

4.      Low transferrin saturation

5.3 Additional Evaluation

1.      Soluble transferrin receptor may be elevated and can help when inflammation complicates ferritin interpretation

2.      Reticulocyte hemoglobin may provide additional evidence of iron-restricted erythropoiesis where available

3.      The Mentzer index may help distinguish iron deficiency from thalassemia trait but is only a screening aid and is not diagnostic

4.      Evaluate for potential causes of iron deficiency, including:

o    Menstrual history

o    Gastrointestinal blood loss

o    Dietary intake

o    Celiac disease

o    Malabsorption

5.4 Evaluation of Gastrointestinal Blood Loss

1.      Do not assume external hemorrhoids are the source of painless rectal bleeding or iron deficiency anemia

2.      External hemorrhoids may explain anal itching and discomfort, while painless bright red bleeding is more characteristic of internal hemorrhoids

3.      Anoscopy should be performed when possible to assess for internal hemorrhoids and other anal canal pathology

4.      Persistent hematochezia with documented IDA requires evaluation for other gastrointestinal causes

5.      Evaluation may include:

o    Colonoscopy, particularly in a patient with persistent hematochezia and IDA

o    Upper gastrointestinal evaluation when clinically indicated

o    Celiac disease testing

6.      Menstrual blood loss should also be carefully assessed in premenopausal women

7.      The extent of evaluation should be individualized according to symptoms, menstrual history, family history, anemia severity, and other gastrointestinal risk factors

6. Differential Diagnosis

1.      Thalassemia trait

2.      Anemia of chronic inflammation

3.      Sideroblastic anemia

4.      Lead toxicity

5.      Other causes of microcytic anemia

7. Management

7.1 Treat the Underlying Cause

1.      Identify and control the source of chronic blood loss

2.      Evaluate persistent rectal bleeding rather than attributing anemia solely to hemorrhoids

3.      If hemorrhoidal disease is confirmed to be clinically important:

o    Treat constipation

o    Increase dietary fiber and fluid intake

o    Reduce straining

o    Use procedural therapy when clinically indicated

7.2 Oral Iron Therapy

1.      Oral iron is first-line therapy for most patients

2.      Ferrous sulfate is commonly used because it is inexpensive and effective

3.      Oral iron should generally be administered once daily at most

4.      Every-other-day dosing may improve tolerability in some patients while maintaining effective absorption

5.      Vitamin C may be used with oral iron to enhance absorption

6.      Avoid taking iron simultaneously with substances that reduce absorption, such as large amounts of calcium or certain antacids

7.3 Intravenous Iron

IV iron should be considered when:

1.      Oral iron is not tolerated

2.      Iron stores fail to improve despite an adequate oral trial

3.      Malabsorption makes oral treatment ineffective

4.      Ongoing blood loss exceeds the ability of oral iron to replace losses

5.      Rapid iron repletion is clinically required

7.4 Monitoring Response

1.      A reticulocyte response generally begins within approximately 1 week

2.      Recheck hemoglobin after approximately 2 to 4 weeks

3.      Hemoglobin should rise progressively with adequate treatment

4.      Continue iron after correction of anemia until iron stores are adequately replenished

5.      An inadequate response should prompt evaluation for:

o    Nonadherence

o    Continued blood loss

o    Malabsorption

o    An alternative diagnosis

8. Complications

1.      Reduced physical and cognitive performance

2.      Restless legs syndrome

3.      Severe anemia may cause tachycardia and cardiac strain

4.      Persistent untreated blood loss may lead to recurrent or severe anemia

9. Key Clinical Insight

Microcytic anemia with low ferritin, low serum iron, high TIBC, low transferrin saturation, and pagophagia is a classic pattern of iron deficiency anemia. Chronic blood loss is likely in this patient, but the presence of external hemorrhoids should not prevent appropriate anorectal and gastrointestinal evaluation for the true bleeding source.

References

1.      DeLoughery TG, Jackson CS, Ko CW, Rockey DC. AGA Clinical Practice Update on Management of Iron Deficiency Anemia: Expert Review. Clin Gastroenterol Hepatol. 2024;22(8):1575-1583. doi:10.1016/j.cgh.2024.03.046.

2.      Ko CW, Siddique SM, Patel A, et al. AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia. Gastroenterology. 2020;159(3):1085-1094. doi:10.1053/j.gastro.2020.06.046.

3.      Qureshi W, Hoang S, Frye J, Rao SS. AGA Clinical Practice Update on Diagnosis and Treatment of Hemorrhoids: Expert Review. Clin Gastroenterol Hepatol. 2026;24(7):1773-1781. doi:10.1016/j.cgh.2026.04.008.