Clinical study
Gastrointestinal causes of refractory iron deficiency anemia in patients without gastrointestinal symptoms☆

https://doi.org/10.1016/S0002-9343(01)00883-XGet rights and content

Abstract

Background

The standard evaluation of a patient with iron deficiency anemia includes a complete evaluation of the gastrointestinal tract to identify a source of bleeding. However, even after a careful examination, many patients remain without a diagnosis. Because iron deficiency anemia results from iron loss or defective absorption, we sought to determine the prevalence of potential gastrointestinal sources for iron deficiency anemia in patients without gastrointestinal symptoms.

Methods

Over a 10-month period, 668 outpatients were referred to the University Hematology Department with iron deficiency anemia, defined by a hemoglobin concentration less than 14 g/dL (less than 12 g/dL in women), mean corpuscular volume less than 80 fL, and ferritin level less than 30 μg/L. After excluding patients with obvious causes of blood loss, inadequate diet, chronic diseases, or malignancies, there were 81 eligible patients, 10 of whom refused investigation. The remaining 71 patients (51 women, median age 59 years) underwent colonoscopy, as well as gastroscopy with gastric (antrum and body) and duodenal biopsies.

Results

A likely cause of iron deficiency anemia was detected in 60 patients (85%). Diseases associated with bleeding were found in 26 patients (37%), including colon cancer (10 patients), gastric cancer (2), peptic ulcer (7), hiatal hernia with linear erosions (5), colonic vascular ectasia (3), colonic polyps (2), and Crohn’s disease (1). Causes not associated with bleeding were found in 36 patients (51%), including 19 with atrophic gastritis, 4 with celiac disease, and 13 with Helicobacter pylori gastritis. Six (8%) patients had coincident gastrointestinal findings, and 11 (15%) had no cause identified. Patients with an identified nonbleeding-associated cause were younger than those with a bleeding-associated cause (median, 56 vs 70 years; P = 0.001) and included 59% of women (n = 30) versus 30% of men (n = 6) (P = 0.04). Hemoglobin level was not related to the site and severity of disease.

Conclusion

Gastrointestinal diseases that do not usually cause bleeding are frequently associated with iron deficiency anemia in patients without gastrointestinal symptom or other potential causes of gastrointestinal bleeding.

Section snippets

Patients

From November 1998 to September 1999, 1202 consecutive outpatients were referred by their primary care physician to the University Hematology Department for consultation. Those with iron deficiency anemia, defined as a hemoglobin concentration less than 14 g/dL for men and less than 12 g/dL for women, a mean corpuscular volume less than 80 fL, and a ferritin level less than 30 μg/L were considered for the study (18). These 668 patients (581 women [87%]; median age, 33 years; range, 21 to 94

Evaluation of patients

All patients underwent gastroscopy with routine antral (n = 3 per patient), body (n = 3), and duodenal (n = 2) biopsies. Additional biopsies were taken from suspicious lesions. Sixty-three patients underwent colonoscopy. The cecum was reached in all patients. During colonoscopy, biopsies were taken from polyps or other suspect lesions. The 8 patients who refused colonoscopy were evaluated with a double-contrast barium enema.

Definitions

Several findings were considered possible causes of blood loss in the

Results

A total of 71 patients underwent a complete evaluation within 7 days (Table 2). All patients had symptoms of iron deficiency anemia (eg, fatigue, dyspnea). None had previously sought medical attention or used medications for gastrointestinal complaints. All but 5 patients had been treated previously with oral iron therapy by their primary care physicians without resolution of anemia. Only 24 (34%) of the patients had previously undergone fecal occult blood testing, which was positive in 9

Discussion

In a sample of consecutive patients referred to a hematology department for iron deficiency anemia, in whom obvious or potential causes of blood loss or other diseases able to cause iron deficiency anemia were excluded, at least one gastrointestinal finding likely to cause iron deficiency anemia was detected in 85% of cases.

The higher yield of our results, compared with studies that considered only diseases that were associated with gastrointestinal bleeding 2, 27, 28, 29, 30, may have been the

Acknowledgements

We thank Mrs. Amelia Pasquali for her technical assistance and Mrs. Annette Pickford for her revision of the English language and style.

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    ☆

    Supported by interuniversity cofinanced program 9906218982 (1999) from the Italian Ministry for University and Scientific and Technological Research (MURST), by a grant from Ministero Sanità (Ricerca Finalizzata d.lgs. 229/99), Rome, Italy, and by Fondazione Italiana per le Malattie Digestive (FIMAD).

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