Anaemia is common among general population in developing Asian countries. Iron deficiency is a common cause of anaemia either due to poor intake or chronic blood loss. Iron deficiency anaemia is usually due to chronic gastrointestinal (GI) blood loss when there is no obvious source of bleeding. The standard of care for these patients with IDA includes evaluation of the Gastrointestinal (GI) tract for bleeding lesions [¹].

Iron deficiency anemia is considered as an alarm sign for the presence of possible GI malignancies, and inadequate evaluation of patients with IDA may delay the diagnosis of GI tumors especially colorectal cancer [²]. In 20% of patients with IDA a routine upper and lower GI endoscopy may not ascertain GI cause during hospital admission [³].

The available literature, in heterogeneous groups including old age patients and postmenopausal women with IDA, has shown GI lesions in 40 – 70% [^4-6]. Studies have shown that increasing age, male gender, ferritin level, prior NSAIDs use, positive fecal occult blood test were factors predictors of endoscopic lesions in patients with IDA with and without GI symptoms [^7-11]. Studies have concluded that prevalence of endoscopic lesions in patients with IDA without GI symptoms is between 48 – 71%, [^9-12] however there is a sparse data related to factors predicting GI lesions in this group.

Important implications for the recognition of iron deficiency anaemia include diagnosis and correction of underlying causes, most of which are identifiable, by means of conventional upper gastrointestinal endoscopy and colonoscopy [¹³] however it remains unresolved which procedure should be done first [³].

Many studies have concluded that on evaluation of Gastrointestinal Tract for IDA; most of the lesions were in lower GI Tract and have recommended that evaluation for IDA should be started with lower GI examination [^14-16].

There is scanty data to predict the nature and site of GI lesions in IDA patients without gastrointestinal symptoms. Therefore there is a need for studies especially from developing asian countries, which may establish endoscopic findings and their predictors in this group.

Primary aim of the study was to identify the predictors of gastrointestinal lesions diagnosed endoscopically in patients with iron deficiency anemia without gastrointestinal symptoms.

This Cross-sectional study performed on a convenience sample of consecutive subjects, conducted from May 2006 to August 2007 at Aga Khan University Hospital.

Two hundred fifty patients underwent endoscopy for iron deficiency anaemia with and without gastrointestinal symptoms during the study period. Ninety five patients met the inclusion criteria. Table 1 shows demographic and biochemical characteristics of patients

Out of ninety five patients endoscopic lesions were found in 50 (52.6%) of patients. Endoscopic lesions were predominantly in upper gastrointestinal tract. Figure 1 shows site of endoscopic lesions in gastrointestinal tract.

Seventeen patients had no obvious endoscopic lesion but on histopathological examination had either helicobacter associated gastritis or celiac disease, the later was confirmed on serologic testing. Table 2 shows etiology for the cause of iron deficiency anaemia in patients without gastrointestinal symptoms.

In upper gastrointestinal tract five patients had malignancy out of which one had oesophageal adenocarcinoma, two had gastric adenocarcinoma, one had gastric lymphoma and one had gastrointestinal stromal tumor (GIST). In lower gastrointestinal tract three patients had ulcerative colitis, two had colonic carcinoma and two had colonic tuberculosis with involvement of cecum and terminal ileum.

On univariate analysis age (p < 0.001), hemoglobin (p = 0.04), MCV ≤ 60 fl (p = 0.003), hemoglobin ≤ 9 gm/dl (p = 0.004), FOB (p < 0.001) and NSAID use (p = 0.04) were significantly related to bleeding related endoscopic lesions (Table 3, 4). On multivariable logistic regression analysis MCV ≤ 60 fl (OR 3.5, 95%CI 1.2 – 10.0), FOB (OR 16.4, 95% CI 3.9 – 67.3) and age (OR 1.05, 95% CI 1.02 – 1.07) were found independent predictors for bleeding related endoscopic lesions in patients with IDA without gastrointestinal symptoms.

For cause of iron deficiency anemia which included bleeding and non bleeding related etiologies; age (p = 0.004), MCV ≤ 60 fl (p < 0.001), hemoglobin ≤ 9 gm/dl (p = 0.06), TIBC (μg/dl) (p = 0.04) and positive fecal occult blood (p = 0.001) were significant factors associated with cause of iron deficiency anemia on univariate analysis. On Multivariable logistic regression analysis after adjusting for confounding factors age in years (OR 1.04, 95% CI 1.01 – 1.08), MCV ≤ 60 fl (OR 14.8, 95% CI 3.6 – 60.7), fecal occult blood positive (OR 7.8, 95% CI 1.46 – 41.8) were independent predictors of the cause of iron deficiency anemia endoscopically (Table 5, 6)

Receiver operating characteristics (ROC) analysis for bleeding related lesions showed area under curve 85% with CI 95% between 77 – 92% while ROC analysis for overall cause of anaemia showed area under curve 88% wit 95% CI between 81–95% (Fig 2 and 3).

Iron deficiency anaemia due to chronic blood loss is usually silent and becomes evident when patients become symptomatic [¹⁹]. Studies in patients with IDA without gastroenterological symptoms are few and have small number of patients and are in different groups of patients. It is difficult to conclude that what is usual pattern of diseases, factor which can predict the endoscopic out come in IDA patients without gastrointestinal symptoms.

We have scanty data in Asian population regarding endoscopic evaluation of IDA patients especially without gastrointestinal symptoms. Furthermore it is unresolved whether evaluation should be started with upper GI or lower GI endoscopic examination.

Available data in patients with IDA having gastrointestinal symptoms the prevalence of getting endoscopic lesions is up to 70% [^4-6] while in asymptomatic IDA patients the cause (bleeding and non-bleeding) was found in 85% [¹¹] and bleeding related lesions were found in 37 – 44% [¹¹,²⁰]. In this study we had 53% of patients with bleeding related cause for IDA and overall cause of IDA (bleeding and non bleeding lesions) was 71% on upper and lower GI endoscopy.

Three patients had celiac disease while14 patients had Helicobacter pylori associated gastritis. It is now recognized that celiac disease can present as IDA without any gastrointestinal symptoms [²¹,²²]. Similarly studies have shown helicobacter pylori infection association with increase in prevalence of IDA [¹¹,¹⁸,²³].

In this cohort, the frequency of lesions involving lower gastrointestinal tract was low which is striking and contrary to the studies in Caucasian population, in which lower GI lesions were more or equal to upper GI tract [²,⁹,¹⁵]. Another prominent finding in our study was small number of patients had malignancies. Only two patients had colonic malignancy which is again dissimilar to the available data which ranges from 10% to 50% patients [¹¹,¹⁵,²⁰,²⁴]. Lower proportion of malignancy in this study may be explained on the basis of lower incidence of gastrointestinal polyps in Asian population [²⁵].

Studies have suggested bidirectional endoscopic evaluation as a workup of IDA and most of them recommended lower gastrointestinal endoscopy first [²⁶,²⁷]. In our study only 10% of patients had colonic involvement while 61% had bleeding and non bleeding causes in upper gastrointestinal tract. Lesions involving both the tracts were present in one patient. Result of this cohort favors that endoscopic evaluation of the upper gastrointestinal tract first.

There is scanty data regarding predictors of endoscopic lesions in IDA patients without GI symptoms, however, hemoglobin, ferritin, female gender and history of NSAIDs have been shown to be associated with endoscopic lesions in patients with IDA having gastrointestinal symptoms [⁸,¹⁰,²⁸]. In the current study there was no correlation with the factors described in patients with GI symptoms. However, our results of advancing age, low mean corpuscular volume and positive fecal occult blood test are in concordance with the available literature of IDA patients.

The main limitation of our study is that we did not investigate patients with negative endoscopies with capsule endoscopy and/or enteroscopy.

In conclusion, patients with iron deficiency anemia without gastrointestinal symptoms obligates comprehensive gastrointestinal tract examination especially with advance age, low mean corpuscular volume and positive fecal occult blood test, as large proportion of patients may have potentially treatable etiology. High proportion of upper gastrointestinal lesions warrants upper gastrointestinal endoscopy as initial endoscopic procedure in patients with iron deficiency anemia with out gastrointestinal symptoms. However these conclusions need validation in further studies.

The authors declare that they have no competing interests.

SM conceived and designed the study, did literature search, collected and analyzed data. SM drafted the initial manuscript. MS was the coordinator of the study. MS helped in analysis and drafted the final manuscript. RW helped in recruitment of study patients. WJ contributed in designing of the study and supervised the study.

All authors read and approved the final manuscript.

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