Original Article

Endoscopy of the Gut: A Window into the Puzzle of

Iron‑deficiency Anemia
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Dr Ajay Kumar1, Col Dharmendra Kumar2, Col Manish Manrai1, Col Sharad Srivastava3, Lt Col Saurabh Dawra4, Brig Alok Chandra4, Col Vishesh Verma1,
Maj Abhinav Kumar1
1
Department of Internal Medicine, AFMC, Pune, Maharashtra, India, 2Department of Gastroenterology, Command Hospital, Udhampur, Jammu and Kashmir, India,
3
Department of Gastroenterology, Command Hospital, Kolkata, West Bengal, India, 4Department of Gastroenterology, Command Hospital, Pune, Maharashtra, India
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Abstract
Background: Iron‑deficiency anemia (IDA) is the most common form of anemia which affects almost every age group. It impacts with varied
severity the quality of life of the person affected. IDA is caused by either decreased availability of food, especially during times of increased
requirement or decreased absorption from the gastrointestinal (GI) tract or increased loss due to various reasons in different age groups. We
tried to estimate the prevalence of GI causes in patients with IDA in a tertiary care hospital and describe the clinicopathological profile of
the patients with IDA. Materials and Methods: A cross‑sectional observational study was conducted in a tertiary care center in Western
India on patients suffering from IDA. Male patients of >18 years and female patients >45 years with IDA and no known chronic disease or
infection were included in the study and their endoscopic/colonoscopic findings were recorded and analyzed. A biopsy was taken, whenever
deemed relevant. Advanced procedures such as enteroscopy or capsule endoscopy were not performed on these patients. Results: A total of
120 patients were evaluated for IDA. At least one GI lesion was found in 42.5% (n = 51) of patients. Upper GI (UGI) lesions (27.5%) were
most commonly encountered, followed by lower GI lesions (9.1%). Conclusion: The patients with unexplained IDA were found to have a
high incidence of GI lesions (42.5%). Hence, evaluation of the GI system with UGI endoscopy, colonoscopy, and mucosal biopsies in relevant
patients is recommended for the determination of the cause of anemia.

Keywords: Colonoscopy, endoscopy, iron‑deficiency anemia, mucosal biopsy

Introduction of causing reduced erythropoiesis.[3‑6] The most common

causes are decreased iron stores due to inadequate iron
Iron is one of the essential micronutrients required to sustain
intake, poor absorption, and increased iron demand and/or
life as it is employed in enzymes and proteins required for the
blood loss.[7‑9] Iron is essential for the production of heme
transportation of oxygen, cellular respiration, cellular growth and
for erythrocytes; as the deficiency increases, it results in a
differentiation, enzymatic reactions, development of immune
decrease in the production of erythrocytes. The effects of
systems, and cognitive and physical growth and development.[1]
these changes lead to the development of microcytic and
Any physiological or pathological cause of deficiency in the
hypochromic anemia.[3,4] IDA rarely occurs in isolation. It is
adult population not only affects the growth and development
usually associated with other conditions such as hookworm
but also the capacity to learn and work. Anemia even when it is
infestation, nutritional deficiency, malabsorption, and
mild impairs the maximal work capacity. As it becomes severe,
hemoglobinopathies.[10,11]
it impairs the work capacity of the population and consequently
the economic output of the country.[2] It is estimated that approximately 1.6 billion people around
the world, i.e., nearly 25% of the world population, have
Iron deficiency is the most common type of chronic anemia
and is defined as the decreased total iron content of the body.
Address for correspondence: Col (Dr) Manish Manrai,
It mostly manifests as iron‑deficiency anemia (IDA) when Department of Internal Medicine, AFMC, Pune ‑ 411 040,
the total iron content of the body is decreased to the extent Maharashtra, India.
E‑mail: manishmanrai75@yahoo.com
Submitted: 26‑Jul‑2023 Revised: 17‑Aug‑2023 Accepted: 26‑Aug‑2023 Published: 29-Feb-2024

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DOI: How to cite this article: Kumar A, Kumar D, Manrai M, Srivastava S,

10.4103/jmms.jmms_114_23 Dawra S, Chandra A, et al. Endoscopy of the gut: A window into the puzzle
of iron‑deficiency anemia. J Mar Med Soc 0;0:0.

© 2024 Journal of Marine Medical Society | Published by Wolters Kluwer - Medknow 1

 Kumar, et al.: Endoscopy in iron‑deficiency anemia
anemia.[12‑15] It is estimated that approximately 50% of anemic
individuals are afflicted with iron deficiency.[9,10] In India, more
than 50% of women and almost 24% of men have been found to
have anemia.[16] The prevalence is especially found to be more
in demographically backward states in the northern and eastern
regions of the country. Children have been elucidated to be
caught in a vicious cycle where chronically deficient mothers
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pass on the burdens of iron deficiency to their daughters,
leading to the propagation of the cycle.[17]
The gastrointestinal tract (GIT) is the site of absorption of
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essential micronutrients, e.g., iron and cobalamin. Most
of GIT diseases relate to malabsorption of these essential
nutrients that subsequently lead to nutritional anemia. In
some GIT disorders, anemia occurs due to bleeding.[18,19] The
most common and frequent gastrointestinal (GI) diseases that
cause anemia include celiac disease, inflammatory bowel
disease (IBD), tropical sprue, intestinal tuberculosis, cystic
fibrosis, and Helicobacter pylori infection.[14,15,20] GI bleeding
due to various causes such as occult gastric or colorectal
malignancy, gastritis, peptic ulceration, chronic use of aspirin
or nonsteroidal anti‑inflammatory drugs, varices, IBD,
diverticulitis, polyp, hemorrhoids, angiodysplasia, hookworm,
and schistosomiasis also causes IDA due to the constant loss
of blood from GIT. Thus, the present study was taken up to
evaluate GI causes in these cases and to assess the need for
such evaluation routinely in such a subset of adult patients
with unexplained anemia.
Materials and Methods
STrengthening the Reporting of OBservational studies
in Epidemiology checklist was adhered to, in this study.
This cross‑section observational study was conducted in
the department of medicine in a tertiary care, referral, and
teaching hospital in Western Maharashtra for a period of
2 years from January 2019 to June 2021. Permission for the
study was taken from the institutional ethical committee. Male
patients of >18 years and female patients >45 years, who
were diagnosed with IDA in outpatient department, or while
being admitted to the hospital, were included in the study. Due
informed consent was taken from each participant. Patients
with chronic kidney disease, chronic infections like HIV or
malaria, females <45 years, or suffering from abnormal uterine
bleeding were excluded from the study.
The demographic data and clinical features of patients
were recorded in a predesigned format. The blood samples
for relevant investigations were collected and analyzed
in the hospital laboratory. All patients were subjected to
fecal occult blood testing before endoscopy. The WHO
definition of anemia were used, i.e., <13 g/dl in males
and <12 g/dl in females. Grading of anemia, according
to the National Cancer Institute, is as follows: mild,
hemoglobin (Hb) – 10.0 g/dL to lower limit of normal;
moderate, Hb – 8.0–10.0 g/dL; severe, Hb – 6.5–7.9 g/dL;
and life‑threatening, Hb <6.5 g/dL.[21]
2 Journal of Marine Medical Society ¦ Volume XX ¦ Issue XX ¦ Month 2024
Microcytic anemia was defined according to cutoffs proposed by
the US Centers for Disease Control and Prevention (>15 years:
<85 fl).[22] Upper GI (UGI) endoscopy was done in all patients
under conscious sedation as and when required. All the
patients were also subjected to esophagogastroduodenoscopy
(EGD) and colonoscopy with cecal intubation using
Penta × 3500 EC‑3840 LK video scope. Any bleeding‑related
endoscopic lesions visualized were biopsied and duodenal
and gastric biopsies were taken if no lesions were found on
endoscopy. The bleeding lesions considered as the cause of
IDA on UGI endoscopy were esophagitis (erosions >5 mm of
the mucosa); gastric and duodenal ulcers (>0.5 cm in diameter);
carcinoma, adenomatous polyps (>0.5 cm in diameter); 5 or
more vascular ectasias; erosive gastritis or duodenitis (multiple
mucosal defects encircled by erythema) or hiatal hernia with
Cameron’s erosions; portal hypertensive gastropathy; and
esophagogastric varices. Nonbleeding UGI causes included
histopathologically proven celiac disease, H. pylori‑associated
chronic gastritis, or atrophic gastritis. The bleeding lesions
considered as the cause of IDA on colonoscopy included
colonic mass, one or more polyps (>0.5 cm in diameter), 5 or
more vascular ectasias, a vascular ectasia >0.7 cm in size,
colonic ulcer (s), and histopathological proven IBD or diffuse
diverticular disease. The automatic hematology analyzer
Beckman Coulter Hematology Analyzer LH 750 (Beckman
Coulter Inc., CA, USA) was used to assess the blood counts.
The levels of thyroid‑stimulating hormone and free thyroxine
were obtained by Beckman Coulter D × 1800 Immunoassay
Analyzer (Beckman Coulter Inc., CA, USA). Serum iron and
total iron‑binding capacity (TIBC) were evaluated using the
colorimetric method, while serum ferritin was performed by
ELISA using a ferritin enzyme immunoassay kit. X‑ray chest,
stool examination, ultrasound of the abdomen and pelvis, bone
marrow aspiration, and biopsy were advised according to the
patient profile.
For maximum sample size, the prevalence of GI causes in
patients with IDA in a tertiary care hospital is assumed to be
50% with a level of confidence of 95% and precision of 7.5%.
The sample size required came to 120 patients. Additional 10%
or 12 patients were recruited to compensate for patient attrition.
Quantitative data were presented with the help of mean and
standard deviation (SD). Comparison among the study groups
was done with the help of an unpaired t‑test as per the results
of the normality test. Qualitative data were presented with the
help of frequency and percentage tables. Association among
the study groups was assessed with the help of the Fisher’s test,
Student’s t‑test, and Chi‑square test (P <0.05 was considered
statistically significant).
Results
The total number of male and female participants was
78 and 42 out of a total of 120 participants [Figure 1].
The male‑to‑female ratio was 1.85 and the approximate
percentage distribution of males and females was 65% and
 Kumar, et al.: Endoscopy in iron‑deficiency anemia
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Figure 1: The figure depicts the result of the study. A total of 120 patients were evaluated in the study and 51 patients (42.5%) were detected with
gastrointestinal lesions. Most commonly encountered lesion was an upper gastrointestinal lesion (27.5%). GI: Gastrointestinal

35%, respectively. The age group of patients ranged from 18

Table 1: Demographic parameters of the participants
to 91 years with a maximum of 26.7% (n = 32) of patients
in the 31–40 years age group. The mean age of the patient’s Variables n=120, n (%)
cohort was 51.5 ± 16.8. Fatigue (53.3%) was the most Gender distribution
common symptom noted by patients, followed by weight Female 42 (65)
loss (28.3%) and effort intolerance (15.8%). Chronic analgesic Male 78 (35)
use was noted in 21.7% of patients and a family history of Age distribution (years), mean±SD 51.5±16.8
carcinoma was noted in 14.2% of all patients. The range of <21 1 (0.8)
Hb values in the included patient was between 3.8 and 11.4 g/ 21–30 8 (6.7)
dl (mean – 7.59 ± 1.68 g%). A total of 66 patients (55%) 31–40 32 (26.7)
41–50 21 (17.5)
had severe anemia (Hb – 6.5–7.9 g%), followed by
51–60 21 (17.5)
45 patients (37.5%) with moderate (Hb – 8–10 g%) and
61–70 17 (14.2)
9 patients (7.5%) with mild anemia.(Hb >10 g%) [Table 1].
71–80 14 (11.7)
The mean corpuscular volume values ranged between 46 and 81–90 5 (4.2)
78.3 fl. A total of 91 patients (75.8%) had mean corpuscular 91–100 1 (0.8)
hemoglobin (MCH) values <27 pg. All patients had MCH History suggestive of anemia
concentration values <32 g/dl. The range of Mentzer’s index was Weight loss 34 (28.3)
14.1–25.1. The majority of participants had a red blood cell count Fatigue 64 (53.3)
between 3 and 4 million/mm3. The range was 2.3–4.7 million Effort intolerance 19 (15.8)
cells/mm3. The range of serum iron values was between 0.2 and Chronic painkiller use 26 (21.7)
49 µg/dl (mean – 12.9 ± 7.9 µg/dl). A total of 97 patients (80.8%) Family history of Ca 17 (14.2)
had extremely low serum ferritin values of 0–10 µg/l. The Prior iron therapy 12 (10.0)
Hemoglobin profile
range of TIBC in participants was between 200 and 530 µg/
Mild 9 (7.5)
dl (mean – 369.6 ± 64.9). The range of transferrin (TF) saturation
Moderate 45 (37.5)
among participants was between 1.6% and 8.6% [Table 2].
Severe 66 (55)
The stomach was the most common site with demonstrable Mean±SD (g %) 7.59±1.68
lesions on evaluation (n = 14, 11.7%), followed by SD: Standard deviation
duodenal (9.2%) and esophageal lesions (5.8%). Multiple
site involvement was noted in 8 patients (6.6%). The most 12%). Esophageal masses were noted in 2 patients and
common lesions on UGI endoscopy were erosions and ulcers varices were noted in 3 patients. Gastric masses/polyps
from the lower esophagus to duodenal regions (n = 21, were present in 4 patients. A total of 33 patients had UGI

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 Kumar, et al.: Endoscopy in iron‑deficiency anemia

lesions (27.5%). Colonic ulcers, masses, and polyps were

Table 2: Blood parameters
present in 5 patients (4.2%). Hemorrhoids and proctitis
were present in 5 cases and a single patient had IBD. Parameters Mean±SD
A total of 11 patients (9.1%) were detected with lower GI MCV (fL) 61.1±6.6
lesions on evaluation. Nonbleeding lesions were detected in Mentzer’s index 18.03±2.5
7 patients (5.8%). We diagnosed two patients (1.7%) with RBC count (/mm3) 3.4±0.5×105
celiac disease on tissue biopsy. A total of 4 patients (3.3%) Serum iron 12.9±7.9
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were detected with H. pylori infection on rapid urease test Serum ferritin 8.1±7.3
and were administered anti‑H. pylori regime by the treating TIBC 369.9±64.9
Tf saturation (%) 4.8±1.3
physicians. One patient had short bowel syndrome (0.8%)
MCV: Mean corpuscular volume, RBC: Red blood cell, TIBC: Total
[Table 3].
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iron‑binding capacity, SD: Standard deviation, Tf: Transferrin

Discussion
Table 3: Site and the types of gastrointestinal lesions
IDA is the scrooge and one of the eminently treatable diseases associated with anemia
in adult populations in developing countries, especially in
women of childbearing age. Unexplained idiopathic IDA in Site of lesion n=120, n (%)
adults has long been suspected due to GI lesions in the Western UGI lesions
population and evaluated in many studies. However, such Duodenal erosions 8 (6.7)
studies are rare in the adult Indian population. Duodenal ulcer 4 (3.3)
Erosive esophagitis 1 (0.8)
Our study was done to evaluate such unexplained IDA in adult Esophageal mass 2 (1.7)
patients attending the out‑ or inpatient services in our tertiary Esophageal varices 3 (2.5)
care teaching hospital. A total of 120 patients underwent GI Esophagitis 2 (1.7)
evaluation for the cause of anemia and were thus included Esophagitis with gastroduodenitis 1 (0.8)
in the final analysis of the study. The reason for the higher Gastric erosions 5 (4.2)
representation of the male gender in our cohort in spite of Gastric mass 1 (0.8)
the higher incidence of anemia in the female population was Gastric polyp 3 (2.5)
mainly due to the exclusion of females in the reproductive Gastric ulcer 3 (2.5)
age group. All the patients in the study were subjected to UGI Lower GI lesions
endoscopy and colonoscopy and mucosal biopsies in addition Colonic polyp/mass 2 (1.7)
Colonic ulcer 3 (2.5)
to other investigations.
Hemorrhoids 4 (3.3)
The mean of the patient’s cohort was 51.5 years with an IBD 1 (0.8)
SD of 16.8 years. In general, the higher age group patients Proctitis 1 (0.8
had more malignant lesions, whereas the younger patients Nonbleeding lesions
did tend to have chronic infections or benign lesions. Celiac disease 2 (1.7)
The majority of patients were in the normal body mass Helicobacter pylori infection 4 (3.3)
index (BMI) range of 18–25 kg/m2. Eight patients (7%) Short bowel 1 (0.8)
were found to be undernourished whereas 13 patients were GI: Gastrointestinal, IBD: Inflammatory bowel disease, UGI: Upper GI
overweight (11%) and one patient was found to be obese. The
average values of distribution (mean ± SD) were 21.7 ± 2.7 kg/ et al.[25] reviewed 95 patients of IDA for evidence of GI lesions
m2. It is to be reiterated that patients with GI lesions had and found the associated cause of anemia in 71% of patients
lower BMI distribution than others without such lesions. with 53% having bleeding lesions. Capsule endoscopy was
Moreover, the majority of colonic and malignant lesions had used by Olano et al.[26] in a study published in 2020, wherein
severe undernourishment. Fatigue was the most common the authors noted GI lesions in unexplained IDA in 50% of
symptom noted by patients, followed by weight loss (mostly cases with 45% of these cases being angiodysplasia. Older
insignificant). studies have been done by multiple authors to delineate GI
A similar study done by Kumar et al.[23] evaluated 102 patients lesions in IDA patients. A study by Rockey et al.[27] followed
of both genders for the cause of anemia in a teaching hospital 409 patients with positive fecal occult blood and found
in India. The protocol of investigations included both UGI bleeding lesions in 48% of patients. Similarly, another study
endoscopy and colonoscopy to observe for GI lesions. In total, by Cook et al.[28] found that 65% of patients had GI lesions
39 patients had demonstrable lesions on UGI endoscopy and out of which 40% had an UGI, 25 patients had lower GI, and
eleven patients demonstrated lower GI lesions. Another study 7 patients had multiple lesions. Another study by McIntyre[29] in
by Odhaib et al.[24] evaluated 398 patients referred for GI 1993 found UGI lesions in 42% of patients and lower GI
evaluation of IDA and found that 102 patients had some UGI lesions in 19% of patients. Kepczyk et al.[30] reported 39% UGI
lesions and another 153 patients had lower GI lesions. Majid lesions, 25% lower GI lesions, and 12% with multiple lesions.

4 Journal of Marine Medical Society ¦ Volume XX ¦ Issue XX ¦ Month 2024

 Kumar, et al.: Endoscopy in iron‑deficiency anemia
This study demonstrated the stomach as the most common site Financial support and sponsorship
with demonstrable lesions (14 patients; 11.7%), followed by Self‑funded.
duodenal lesions (9.2%) and esophageal lesions (5.8%). Multiple
site involvement was noted in 8 cases. The most common lesions Conflicts of interest
on UGI endoscopy were erosions and ulcers from the lower There are no conflicts of interest.
esophagus to duodenal regions (21 patients; duodenal erosions
in 8 patients and gastric in 5 patients). Esophageal mass and References
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varices were noted in 3 patients each. Gastric masses/polyps 1.
were present in 4 patients. In the study by Kumar et al.,[23] antral
gastritis was the most common lesion followed by D and
2.
D2 ulcers. Similar to this study, Odhaib et al.[24] also found
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gastritis and erosions to be the most common UGI lesion. In
contrast to all these studies, Cook et al.[28] found esophagitis to 3.
be equal in frequency to gastric and duodenal erosions in their
investigations. Overall, 27.5% of our patients have UGI lesions, 4.
which was much lower in frequency than in all these studies.
5.
Colonic lesions, namely, ulcers, masses, and polyps, were
documented in 5 patients (4%). Hemorrhoids and proctitis 6.
were present in 5 cases and a single patient had IBD. Thus,
11 patients (9.2%) were detected with lower GI lesions 7.
on evaluation. Nonbleeding lesions were found in only
7 cases (5.8%). Three patients had celiac disease confirmed 8.
with tissue biopsy. Four patients were detected with H. pylori
infection on breath tests and were administered anti‑H. pylori
9.
regime by the treating physicians. It was comparable to the
frequency of lower GI lesions described by Kumar et al.[23] In 10.
comparison, both Odhaib et al.[24] and Cook et al.[28] found a
much higher number of intestinal and colonic lesions.
11.
Conclusion and Recommendations
12.
The patients with unexplained IDA were found to have a high
incidence of GI lesions. The most common lesions were gastric
and esophageal erosions. Hence, we recommend evaluation 13.
of the GI system with UGI endoscopy, colonoscopy, and
mucosal biopsies in relevant patients to evaluate for the cause 14.
of unexplained IDA. Endoscopy in our patients indeed acted
as a window into the etiology of unexplained IDA [Box 1].
15.
Acknowledgments
We acknowledge the support provided by the Department of 16.
Pathology, AFMC, Pune.
17.
Box 1: Findings of the study 18.
What is already known about this subject?
IDA is associated with chronic GI blood loss
GI lesions can give rise to decreased absorption of iron or increased 19.
utilization and depletion of iron stores in setting of chronic GI blood loss
What are the new findings?
20.
The association between the presence of a GI lesion in cases of IDA in
the Indian context was found to be approximately 42.5%
UGI lesions were found to be most commonly associated with IDA. 21.
The most common lesions found were gastric and oesophagal erosions
American Gastroenterology Association recommends bi‑directional
endoscopy for evaluation of IDA. Consistent with these guidelines we 22.
strongly recommend endoscopy for evaluation of GI etiology in IDA
GI: Gastrointestinal, UGI: Upper GI, IDA: Iron‑deficiency anemia
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6 Journal of Marine Medical Society ¦ Volume XX ¦ Issue XX ¦ Month 2024