Journal Information
Vol. 40. Num. 3.July - September 2018
Pages 199-292
Share
Share
Download PDF
More article options
Visits
287
Vol. 40. Num. 3.July - September 2018
Pages 199-292
Original article
DOI: 10.1016/j.htct.2018.02.001
Open Access
Helicobacter pylori associated to unexplained or refractory iron deficiency anemia: an Egyptian single-center experience
Visits
287
Doaa M. El Demerdash
Corresponding author
dr_eldemerdash@kasralainy.edu.eg

Corresponding author at: Kasr AL-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Egypt.
, Heba Ibrahim, Dina M. Hassan, Heba Moustafa, Nehad M. Tawfik
Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt
This item has received
287
Visits
Article information
Abstract
Full Text
Bibliography
Download PDF
Statistics
Figures (2)
Tables (5)
Table 1. Data of patients with refractory or unexplained iron deficiency anemia.
Table 2. Non-parametric data of patients with refractory or unexplained iron deficiency anemia.
Table 3. Clinical and laboratory comparison between H. pylori-positive and -negative patients.
Table 4. Laboratory data comparing H. pylori eradication with iron supplementation (Group A) and iron supplementation alone (Group B).
Table 5. Helicobacter pylori associated unexplained iron deficiency anemia in comparable studies.
Show moreShow less
Abstract
Background

Refractory or unexplained iron deficiency anemia accounts for about 15% of all cases. The endoscopic gastrointestinal workup sometimes fails to establish the cause of iron deficiency anemia and a considerable proportion of patients regardless of risk category fail to respond to oral iron supplementation. The aim of the present study was to assess the etiological role of Helicobacter pylori infection in adult Egyptian patients with unexplained or refractory iron deficiency anemia.

Methods

A case controlled study was composed of 104 iron deficiency anemia cases and 70 age- and gender-matched healthy controls. Patients were diagnosed with iron deficiency anemia according to hemoglobin, mean corpuscular volume, serum ferritin, and transferrin saturation. Upper and lower endoscopies were performed and active H. pylori infection was investigated by testing for the H. pylori antigen in stool specimens. Hematological response to H. pylori treatment with triple therapy together with iron therapy (n=32) or only iron therapy (n=32) were assessed in patients with H. pylori infection.

Results

H. pylori infection was more prevalent in patients with unexplained or refractory iron deficiency anemia (61.5%). Of the different hematological parameters investigated, there was a significant correlation only between H. pylori infection and mean corpuscular volume (p-value 0.046). Moreover, there was a significant correlation between receiving triple therapy together with iron supplementation and improvements in the hematological parameters [hemoglobin (p-value<0.001), mean corpuscular volume (p-value<0.001), iron (p-value<0.001) and serum ferritin (p-value<0.001)] compared to receiving iron supplementation alone.

Conclusions

Failing to test for H. pylori infection could lead to a failure to identify a treatable cause of anemia and could lead to additional and potentially unnecessary investigations. Furthermore, treatment of H. pylori infection together with iron supplementation gives a more rapid and satisfactory response.

Keywords:
Helicobacter pylori
Iron deficiency anemia
Refractory iron deficiency
Unexplained iron deficiency
Microcytic anemia
Full Text
Introduction

Iron deficiency anemia (IDA) is a worldwide nutritional problem; it accounts for about half of the world's anemia burden with most IDA patients living in developing countries.1

Refractory or unexplained IDA accounts for about 15% of all cases.2 It is a diagnostic and evaluation challenge that employs a list of exams from stool testing for parasitic infestations to full gastroenterology endoscopies.3 The term ‘unexplained IDA’ can be applied when the endoscopic gastrointestinal workup fails to establish the cause of IDA.4 On the other hand, the term ‘refractory IDA’ is applied to a considerable proportion of patients when they fail to respond to iron supplementation at a dose of at least 100mg of elemental iron per day over 4–6 weeks.2

It is estimated that Helicobacter pylori infects the stomachs of 50% of the global population. There are variations in infection rates from one country to another with the rates being inversely correlated with the human development index.5

Without eradication treatment, H. pylori is likely to persist in its human host for a lifetime with a proportion of infected individuals developing peptic ulcers, gastric adenocarcinomas and/or mucosa associated lymphomas (MALT). Beyond the stomach, more than 50 extra-gastric manifestations of H. pylori have been reported involving a wide list of medical disorders.6

The relationship between H. pylori and iron deficiency was first described in 1991 as a 15-year-old boy with IDA had improved hematological parameters after H. pylori eradication.7 The mechanisms underlying the association between H. pylori infection and iron deficiency are not fully understood yet. The most obvious mechanism for H. pylori to cause IDA is by competing for dietary iron. H. pylori requires higher concentrations of inorganic iron and zinc than other pathogens for in vitro growth, yet there is no evidence that H. pylori has more iron- or zinc-dependent enzymes than other bacteria.8

Data on the effect of H. pylori eradication on adult Egyptian patients with refractory IDA or IDA of unknown origin, a population with a high prevalence of H. pylori, are scarce. The objectives of this study are to evaluate the prevalence of H. pylori infection among a cohort of Egyptian patients with unexplained iron deficiency anemia and to investigate the relationship between H. pylori infection and the hematological parameters of these patients. Furthermore, this study aimed to assess the patients’ response to combined H. pylori triple therapy with iron therapy compared to iron therapy alone.

Methods

A total of 104 Egyptian subjects who were diagnosed with IDA of unknown cause or who were refractory to oral iron therapy (60 women and 44 men with a mean age of 39.6±10.84 years) and 70 age- and gender-matched healthy controls were enrolled in this study. All subjects were consecutively recruited in the Clinical Hematology Unit of the Kasr Al-Ainy Teaching Hospital, Cairo University where they were diagnosed and followed-up prospectively between October 2014 and June 2017. The study complied with good clinical practice protocols and with the ethical norms stated in the Declaration of Helsinki (as revised in Tokyo 2004). The study was approved by the local Ethics Committee and all patients gave their written informed consent prior to recruitment.

All subjects with unexplained or refractory iron deficiency anemia as well as healthy controls were subjected to full history taking (especially nutritional and menstrual data, drugs taken, bleeding or gastrointestinal history as well as compliance to iron therapy), a thorough physical examination, and laboratory tests. The laboratory investigations included a complete blood count (CBC) and blood film, reticulocyte count, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and liver and kidney function as well as upper and lower endoscopies. Patients with malignancies, chronic diseases, dimorphic anemia, obvious causes of IDA and acute infections were excluded from the study.

Diagnosis of iron deficiency anemia

All patients had hemoglobin levels less than reference values for age and gender with a blood film that showed microcytic hypochromic anemia. The mean corpuscular volume (MCV) was less than 80fl, serum ferritin was below 20ng/dL; iron was below 50g/dL and total iron binding capacity (TIBC) was more than 350g/dL. The transferrin saturation was below 15%. Ferritin was measured using the Elecsys 2010 system using a Roche diagnostics kit by the electro-chemiluminescence immunoassay (ECLIA) method. Serum levels of iron were measured by the colorimetric method with a Roche modular analyzer. TIBC was measured with the Roche modular analyzer.

Diagnosis of H. pylori infection

Stool specimens were collected from participants (patients as well as healthy controls) and tested for the H. pylori antigen using the H. pylori Ag test (CTK Biotech, Inc. San Diego, CA 92121, USA. Cat # R0192C). This is a sandwich lateral flow chromatographic immunoassay that uses a colloidal gold conjugated monoclonal anti-H. pylori antibody and a second monoclonal anti-H. pylori antibody to specifically detect the H. pylori antigen present in fecal specimens. The detection limit for the spectrum H. pylori Ag test device is a 5ng/mL H. pylori lysate.

Therapy response assessment

Patients who were discovered to have H. pylori infection were randomly subdivided into two groups:

Group A: received triple therapy for H. pylori eradication (omeprazole 20mg b.i.d., amoxicillin 1g b.i.d. and clarithromycin 500mg b.i.d.) for 14 days combined with oral iron therapy (ferrous sulphate 325mg OD) for three months.

Group B: received only oral iron therapy (ferrous sulphate 325mg OD) for three months.

After three months of therapy, Group A and Group B were both reassessed regarding hemoglobin, MCV, mean corpuscular hemoglobin (MCH), serum iron, and ferritin levels with H. pylori eradication being evaluated by the detection of the H. pylori antigen in stools.

Statistical analysis

Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 23. Data was summarized using means, standard deviation (SD), median, minimum and maximum in quantitative data and using absolute frequencies (count) and relative frequencies (percentage) for categorical data. Comparisons between quantitative variables were achieved using the non-parametric Kruskal–Wallis and Mann–Whitney tests. The Chi-square (χ2) test was used to compare categorical data. Fisher's exact test was used when the expected frequency was less than 5. p-Values less than 0.05 were considered statistically significant.

Results

The patients enrolled in this study included 60 females (63.5%) and 44 males (42.3%) with ages ranging between 19 and 65 years (mean age: 39.6±10.84 years). The healthy controls were 36 (51.4%) females and 34 males (48.5%) with ages ranging between 20 and 62 years (mean age: 39.6±10.84 years).

The duration of IDA of the patients ranged from 0.9 to 8 years (mean: 3.8±1.6 years); all had unexplained causes for IDA. All patients had unremarkable physical examinations and the gynecological examinations of all the women were normal. Patient characteristics are summarized in Tables 1 and 2.

Table 1.

Data of patients with refractory or unexplained iron deficiency anemia.

Parameter  Range  Mean±SD 
Age (years)  (19–65)  39.67±10.84 
Duration of IDA (years)  (0.9–8)  3.83±1.66 
WBC (cells×109L–1(4–16)  7.5±3.4 
Hemoglobin (g/dL)  (5.8–10)  8.08±0.99 
MCV (fl)  (59–75)  68.1±3.89 
MCH (pg)  (17–25)  20.04±1.73 
Platelets (cells×109L–1(149–750)  333±122 
Reticulocyte (%)  (0.5–4)  2.06±0.86 
ESR (mm/h)  (10–90)  37.71±16.38 
IRON (g/dL)  (6–40)  22.8±10.89 
TIBC (g/dL)  (350–520)  387±72 
TS (%)  (1–14)  5.4±2.6 
Ferritin (ng/dL)  (1–20)  7.7±5.3 
ALT (IU/L)  (10–50)  30.65±18.8 
AST (IU/L)  (15–45)  32.46±19.3 
LDH (IU/L)  (95–300)  181.15±52.14 
ALB (mg/dL)  (3.5–5)  3.78±0.55 
PC (%)  (72–100)  95.81±5.3 
Creatinine (mg/dL)  (0.6–1.4)  1.1±0.18 

SD: standard deviation; IDA: iron deficiency anemia; WBC: white blood cell count; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin; ESR: erythrocyte sedimentation rate; TIBC: total iron binding capacity; TS: transferrin saturation; ALT: alanine transaminase; AST: aspartate transaminase; LDH: lactate dehydrogenase; ALB: albumin.

Table 2.

Non-parametric data of patients with refractory or unexplained iron deficiency anemia.

Parameter    n 
SexMale  44  42.3 
Female  66  63.5 
Previous iron therapyYes  74  71.1 
No  30  28.8 
Previous blood transfusionYes  38  36.5 
No  66  63.4 
Upper endoscopyNo abnormalities  66  63.4 
Mild gastritis  30  28.8 
Antral erosions  7.69 
ColonoscopyNormal  60  57.6 
Nonspecific colitis  44  42.3 
H. pylori Ag in stoolsPositive  64  61.5 
Negative  40  38.4 

The H. pylori Ag test was positive in 64 out of 104 (61.5%) patients and in 10 (14.3%) non-anemic healthy controls; the difference between the two groups was statistically significant (p-value<0.001; Figure 1).

Figure 1.
(0.05MB).

Prevalence of H. pylori between unexplained-refractory iron deficiency anemia and control groups. IDA: Unexplained-refractory iron deficiency anemia group (n=104); HC: healthy control group (n=70). *Mean values were significantly different between groups (p-value<0.001).

Patients were sub-divided into two groups according to H. pylori Ag status; Group I (H. pylori Ag Positive) and Group II (H. pylori Ag negative). A correlation analysis was performed with the clinical and laboratory features as summarized in Table 3; there was a significant correlation between H. pylori status and MCV (p-value=0.046), otherwise there were no significant correlations with other parameters including the iron parameters.

Table 3.

Clinical and laboratory comparison between H. pylori-positive and -negative patients.

Parameter  H. pylori statusp-Value 
  Group I positive (n=64)Group II negative (n=40) 
  Range  Mean±SD  Range  Mean±SD   
Age (years)  (19–65)  40.8±11.1  (20–55)  37.8±10.33  0.342 
Duration of IDA (years)  (1–8)  4.06±1.71  (0.9–7)  3.45±1.53  0.197 
WBC (cells×109L–1(4.5–14.5)  7.6±3.4  (4–16)  7.3±3.6  0.588 
Hemoglobin (gm/dL)  (5.8–9.9)  8.1±1.02  (6.8–10)  7.9±0.9  0.877 
MCV (fl)  (60–73)  66.7±3.5  (59.8–75)  68.9±3.9  0.046a 
MCH (pg)  (17–22)  19.4±1.43  (17–25)  20.4±1.82  0.057 
Platelets (cells×109L–1(149–750)  334.2±116.1  (160–690)  331.1±135.4  0.930 
Reticulocyte (%)  (0.8–3.3)  2.03±0.74  (0.5–4)  2.09±1.04  0.873 
Serum Iron (g/dL)  (6–35)  22.6±8.3  (6–40)  23.04±14.3  0.734 
TIBC (g/dL)  (350–504)  381.6±31.4  (352–520)  397.5±45.8  0.446 
TS (%)  (1–10.6)  5.6±2.3  (1–14)  5.2±3.03  0.067 
Ferritin (ng/dL)  (1–20)  7.8±5.7  (2.5–20)  7.5±4.8  0.977 

SD: standard deviation; IDA: iron deficiency anemia; WBC: white blood cell count; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin; TIBC: total iron binding capacity; TS: transferrin saturation.

a

Significantly difference (p-value<0.05).

Group I (H. pylori positive) was further randomly divided into two groups; Group A (32 patients) received triple therapy plus oral iron supplementation and Group B (32 Patients) received only oral iron supplementation. These patients were reassessed after three months. The flowchart of the study is shown in Figure 2 and the data are summarized in Table 4.

Figure 2.
(0.07MB).

Flowchart of study group. IDA: iron deficiency anemia.

Table 4.

Laboratory data comparing H. pylori eradication with iron supplementation (Group A) and iron supplementation alone (Group B).

Parameter  Group (A) (n=32)p-Value 
  Before therapy  After 3 months of therapy   
  Mean±SD  Mean±SD   
Hemoglobin (g/dL)  8.10±1.04  11.9±0.86  <0.001a 
MCV (fl)  69.09±4.64  79.75±4.07  <0.001a 
MCH (pg)  21.02±1.94  27.78±0.99  <0.001a 
Serum Iron (g/dL)  20.56±7.96  91.25±16.68  <0.001a 
TIBC (g/dL)  381.6±31.4  200±45.8  <0.001a 
TS (%)  5.6±2.3  45.62±3.03  <0.001a 
Ferritin (ng/dL)  7.8±5.7  25±4.8  <0.001a 
Parameter  Group (B) (n=32)p-Value 
  Before therapy  After 3 months of therapy   
  Mean±SD  Mean±SD   
Hemoglobin (g/dL)  8.17±1.04  8.61±1.05  0.083 
MCV (fl)  68.81±3.21  71.44±5.23  0.074 
MCH (pg)  19.78±1.51  21.97±4.22  0.092 
Serum Iron (g/dL)  24.75±8.59  27.31±19.96  0.068 
TIBC (g/dL)  385.4±33.1  370.1±42.7  0.067 
TS (%)  6.4±2.3  7.38±4.03  0.068 
Ferritin (ng/dL)  7.9±5.1  11±2.8  0.059 

SD: standard deviation; IDA: iron deficiency anemia; WBC: white blood cell count; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin; TIBC: total iron binding capacity; TS: transferrin saturation.

a

Significantly difference (p-value<0.05).

Group A was comprised of 14 males and 18 females while Group B consisted of 16 males and 16 females. Group A showed statistically significant improvements in the hemoglobin level, MCV, MCH, serum iron and ferritin after three months of therapy (p-value<0.001, 0.001, 0.001, 0.001, 0.001, respectively). On the other hand, Group B had no statistically significant improvements in hemoglobin level, MCV, MCH, serum iron or ferritin (p-value: 0.083, 0.074, 0.092, 0.068 and 0.059, respectively). H. pylori was eradicated in all 32 patients of Group A.

Discussion

Refractory or unexplained IDA accounts for about 15% of all IDA. It is a diagnostic challenge with evaluations that include a set of tests starting with stool testing for parasites and continuing up to full gastroenterology endoscopies. Endoscopic gastrointestinal workups sometimes fail to establish the cause of IDA and a considerable proportion of patients regardless of risk category fail to respond to oral iron supplementation.9 The prevalence of H. pylori is not homogenous worldwide; it varies depending on age, country of origin and socioeconomic conditions. The Egyptian Demographic Health Survey reported a prevalence of H. pylori infection in 6.6% of Egyptian adults.10 The aim of the present study was to assess the etiological role of H. pylori infection in adult Egyptian patients with unexplained or refractory IDA.

This study found that H. pylori infection was more prevalent in patients with unexplained or refractory IDA (61.5%) compared to healthy controls (14.3%) with these results possibly suggesting that H. pylori infection is one cause of IDA in adult patients with unexplained or refractory IDA for whom the standard diagnostic work-up is negative. These data are corroborated by many other studies that reported high prevalences of H. pylori in patients with unexplained or refractory IDA. For example, Hershko et al. found that H. pylori infection was the common coexisting finding in 55% of 300 patients with unexplained IDA.11 However, a study by Santos et al., conducted in 2149 children from Latin America did not find any significant association between H. pylori infection and IDA.12 Furthermore, studies performed in Brazil,13 South Korea,14 Sweden15 and Iran16 were not successful in finding any significant association between the prevalence of H. pylori infection and IDA.

The present study only found a significant difference in MCV between H. pylori-positive and H. pylori-negative groups. It was not expected to find any other differences especially in respect to iron parameters, as for many years different studies demonstrated an association between H. pylori infection and decreasing iron status. Some found an association between H. pylori infection and decreasing ferritin levels.17 A large study conducted in 1040 children in Alaska by Parkinson et al. found a significant association between low serum ferritin levels and the prevalence of H. pylori infection.18 A German study found significantly lower levels of hemoglobin in pregnant women suffering from H. pylori infection.19 Moreover, an American study conducted in 7462 healthy individuals found that those who were seropositive for H. pylori infection had significantly lower serum ferritin levels compared with seronegative individuals.20 Even so, an Egyptian study conducted with 90 chronic kidney disease patients on hemodialysis also found no significant differences between H. pylori-positive and -negative groups for any of the variables analyzed including hemoglobin, serum iron, ferritin and transferrin saturation.21 In addition, an Egyptian study conducted in 60 children found that the soluble transferrin receptor in serum was significantly higher in the H. pylori-positive group compared to the H. pylori-negative group although no significant differences were noted in hematologic variables and iron parameters between the two groups.22 This variability in studies could be due to differences in the geographical and ethnical distribution of patients, age, inclusion criteria, sample size, sampling procedures, methods of detecting anemia, and methods of detecting H. pylori infection.

Regarding the therapeutic intervention, there was marked improvement in hemoglobin level, Three months of therapy had a statistically significant effect on MCV and iron parameters in the arm that combined triple therapy with oral iron supplementation compared to the arm of oral iron therapy alone. This is considered the most reliable evidence for a cause–effect relationship between H. pylori infection and unexplained iron deficiency. This result corroborated many other studies that showed that the eradication of H. pylori, with or without iron supplementation, was followed by improvements in hemoglobin levels. However, other studies did not reveal such clear improvements in the markers of iron deficiency as shown in Table 5. These studies suggested that the treatment of H. pylori infection is important to reduce the IDA burden worldwide. On the contrary, one study conducted in 200 children in Bangladesh, a country with a high prevalence of H. pylori, found that H. pylori is neither a cause of IDA/iron deficiency nor a reason for failure of iron supplementation.23 Furthermore, a study conducted in 18 school-aged cases of IDA with H. pylori infections in Saudi Arabia reported no significant improvement in serum ferritin levels with the use of anti-H. pylori treatment without iron supplementation.24

Table 5.

Helicobacter pylori associated unexplained iron deficiency anemia in comparable studies.

Studies  Study group  H. pylori detection  Study design  Conclusions 
El-Aziz Awad et al., Egypt [22]  Children  H. pylori serum IgG antibodies  Group (A): Anti H. pylori and Oral iron (n=20)
Group (B): Anti H. pylori (n=20)
Group (C): oral iron (n=20) 
Improvement of iron parameters were significantly greater in groups of children who received anti-HP therapy either combined with iron or alone 
Nashaat et al., Egypt [25]  Pregnant women  H. pylori serum IgG antibodies  All patients received oral iron (n=100) after 1 month H. pylori positive cases (n=50) received anti H. pylori and oral iron  Hb in cases negative to H. pylori was higher than those positive to H. pylori.
It was found that rise of Hb was higher after treatment than before eradication of H. pylori
Kotb et al., Egypt [26]  IDA adults  Gastric biopsy for H. pylori  20 patients received sequential eradication therapy for followed by oral iron therapy.  Improvement in hematological parameters and serum iron profile was observed post successful H. eradication and oral iron therapy. 
Xia et al., China [27]  Adolescent girls  Serum H. pylori IgG antibodies and stool antigen EIA  Group (A): oral iron and anti H. pylori (n=32)
Group (B): oral iron (n=42) 
Treatment of H. pylori infection is associated with a more rapid response to oral Fe therapy 
Malik et al., India [28]  Pregnant women  H. pylori stool antigen  Group (A): anti H. pylori and oral iron and folic acid (n=19)
Group (B): oral iron and folic acid (n=19) 
Eradication therapy resulted in significantly better response to oral iron supplementation among H. pylori infected pregnant women with IDA. 
Cardenas et al., Texas [29]  Children (3–10) years  Urine H. pylori
IgG antibody and l3C-Iabeled urea breath tests 
Group (A): Both anti H. pylori and oral iron (n=32).
Group (B): anti H. pylori sequential (n=29)
Group (C): oral Iron (n=23)
Group (D): Placebo only (n=26) 
They found that those who had their infection eradicated had a 3-fold increased average change from baseline serum ferritin compared with that of children who remained infected 
Sarker et al., Bangladesh [23]  Children (2–5) years  l3C-Iabeled urea breath tests  Group (A): anti H. pylori and oral iron (n=50).
Group (B): anti H. pylori (n=50).
Group (C): oral iron (n=49)
Group (D): Placebos only (n=51) 
H. pylori is neither a cause of IDA/ID nor a reason for treatment failure of iron supplementation in young Bangladeshi children 
Vijayan et al., India [30]  13 years or older  Rapid urease test and histology  Group (A): anti H. pylori and oral iron (n=11)
Group (B): oral iron (n=11) 
Treatment for both anemia and H. pylori infections is required for lowering the levels of lipid peroxides in those patients. 
Chen and Luo, China [31]  IDA adults  l3C-Iabeled urea breath tests  Group (A): anti H. pylori and oral iron (n=43)
Group (B): Oral iron (n=43) 
Successful H. pylori eradication resulted in a significant post-treatment an increase in the peripheral complete blood count and serum iron. 
Gessner et al., USA [32]  Children (7–11) years  l3C-Iabeled urea breath tests  Group (A): anti H. pylori and oral iron (n=79)
Group (B): oral iron (n=113) 
In a high-prevalence population, treatment and resolution of H. pylori infection did not improve isolated iron deficiency or mild anemia up to 14 months after treatment initiation. 
Choe et al., South Korea [33]  Adolescent female athletes  Rapid urease test and histology  Group (A): anti H. pylori (n=12)
Group (B): oral iron (n=9) 
Significant increases in iron parameters after H. pylori eradication while no significant changes in subjects who were treated orally with iron alone 
Choe et al., South Korea [34]  Preadolescent children and adolescents  Rapid urease test and histology  Group A: anti H. pylori and oral iron.
Group B: only anti H. pylori.
Group C: only oral iron. 
Treatment of H. pylori infection was associated with a more rapid response to oral iron treatment than the use of iron alone 

In conclusion, the present study suggests that there is an association between H. pylori infection and refractory or unexplained IDA in adult Egyptian patients. In cases of IDA and co-existing H. pylori infection, IDA can be treated by the eradication of H. pylori in combination with iron supplementation. Failing to test for H. pylori infection could lead to a failure to identify a treatable cause of anemia and could lead to additional and potentially unnecessary investigations. Moreover, treatment of H. pylori infection together with iron therapy may give a more rapid and satisfactory response.

Authors’ contributions

Meticulous laboratory work done under the supervision of Dr. Dina M Hassan. Article written by Dr Doaa M El Demerdash, Data collection and Patient follow up by Dr. Heba Ibrahim. The article was revised by all authors.

Conflicts of interest

The authors declare no conflicts of interest.

Acknowledgments

We deeply thank all of our patients who accepted to participate in this study. In addition, we thank Dr. Mohamed Ali Eshra, Lecturer of Human Physiology, Faculty of Medicine, Cairo University, for his meticulous statistical work.

References
[1]
S.R. Pasricha,H. Drakesmith,J. Black,D. Hipgrave,B.A. Biggs
Control of iron deficiency anemia in low- and middle-income countries
[2]
C. Hershko,C. Camaschella
How I treat unexplained refractory iron deficiency anemia
[3]
M.W. Short,J.E. Domagalski
Iron deficiency anemia: evaluation and management
Am Fam Physician, 87 (2013), pp. 98-104
[4]
D.C. Rockey,J.P. Cello
Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia
N Engl J Med, 329 (1993), pp. 1691-1695 http://dx.doi.org/10.1056/NEJM199312023292303
[5]
M. Amieva,R.M. Peek Jr.
Pathobiology of Helicobacter pylori – induced gastric cancer
Gastroenterology, 150 (2016), pp. 64-78 http://dx.doi.org/10.1053/j.gastro.2015.09.004
[6]
T.L. Testerman,J. Morris
Beyond the stomach: an updated view of Helicobacter pylori pathogenesis, diagnosis, and treatment
World J Gastroenterol, 20 (2014), pp. 12781-12808 http://dx.doi.org/10.3748/wjg.v20.i36.12781
[7]
U. Blecker,F. Renders,S. Lanciers,Y. Vandenplas
Syncopes leading to the diagnosis of a Helicobacter pylori positive chronic active haemorrhagic gastritis
Eur J Pediatr, 150 (1991), pp. 560-561
[8]
T.L. Testerman,P.B. Conn,H.L. Mobley,D.J. McGee
Nutritional requirements and antibiotic resistance patterns of Helicobacter species in chemically defined media
J Clin Microbiol, 44 (2006), pp. 1650-1658 http://dx.doi.org/10.1128/JCM.44.5.1650-1658.2006
[9]
J.F. Dahlerup,M. Eivindson,B.A. Jacobsen,N.M. Jensen,S.P. Jorgensen,S.B. Laursen
Diagnosis and treatment of unexplained anemia with iron deficiency without overt bleeding
Dan Med J, 62 (2015), pp. C5072
[10]
F. El Zanaty,A. Way
Egypt Demographic and Health Survey 2005. Ministry of Health and Population, National Population Council
El Zanaty and Associates and ORC Macro, (2006)pp. 169-187
[11]
C. Hershko,A.V. Hoffbrand,D. Keret,M. Souroujon,I. Maschler,Y. Monselise
Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia
Haematologica, 90 (2005), pp. 585-595
[12]
I.S. Santos,J. Boccio,L. Davidson,M. Hernandez-Triana,E. Huanca-Sardinas,M. Janjetic
Helicobacter pylori is not associated with anemia in Latin America: results from Argentina, Brazil, Bolivia, Cuba, Mexico and Venezuela
Public Health Nutr, 12 (2009), pp. 1862-1870 http://dx.doi.org/10.1017/S1368980009004789
[13]
L.N. Araf,C.A. Pereira,R.S. Machado,D. Raguza,E. Kawakami
Helicobacter pylori and iron-deficiency anemia in adolescents in Brazil
J Pediatr Gastroenterol Nutr, 51 (2010), pp. 477-480 http://dx.doi.org/10.1097/MPG.0b013e3181d40cd7
[14]
J.W. Choi
Does Helicobacter pylori infection relate to iron deficiency anemia in prepubescent children less than 12 years of age?
Acta Paediatr, 92 (2003), pp. 970-972
[15]
G. Sandström,S. Rödjer,B. Kaijser,M. Börjesson
Helicobacter pylori antibodies and iron deficiency in female adolescents
[16]
A. Zamani,M. Shariat,Z.O. Yazdi,S. Bahremand,P.A. Asbagh,A. Dejakam
Relationship between Helicobacter pylori infection and serum ferritin level in primary school children of Tehran-Iran
J Pak Med Assoc, 61 (2011), pp. 658-661
[17]
S.H. Gheibi,H.R. Farrokh-Eslamlou,M. Noroozi,A. Pakniyat
Refractory iron deficiency anemia and Helicobacter pylori infection in pediatrics: a review
Iran J Ped Hematol Oncol, 5 (2015), pp. 50-64
[18]
A.J. Parkinson,B.D. Gold,L. Bulkow,R.B. Wainwright,B. Swaminathan,B. Khanna
High prevalence of Helicobacter pylori in the Alaska Native Population and association with low serum ferritin levels in young adults
Clin Diagn Lab Immunol, 7 (2000), pp. 885-888
[19]
M. Weyermann,D. Rothenbacher,L. Gayer,G. Bode,G. Adler,D. Grab
Role of Helicobacter pylori infection in iron deficiency during pregnancy
Am J Obstet Gynecol, 192 (2005), pp. 548-553 http://dx.doi.org/10.1016/j.ajog.2004.08.028
[20]
V.M. Cardenas,Z.D. Mulla,M. Ortiz,D.Y. Graham
Iron deficiency and Helicobacter pylori infection in the United States
Am J Epidemiol, 163 (2005), pp. 127-134 http://dx.doi.org/10.1093/aje/kwj018
[21]
H. El-Said,A.B. Attallah,Z.A. Ali-Eldin
Does Helicobacter pylori infection play a role in iron deficiency anemia in hemodialysis patients?
Clin Nephrol, 88 (2017), pp. 177-180 http://dx.doi.org/10.5414/CN109034
[22]
M.-D. El-Aziz Awad,S.M. Amin,S.M. Abdou
Assessment of diagnostic and therapeutic approaches of Helicobacter pylori-associated iron deficiency and anemia in children with dyspeptic symptoms
J Egypt Soc Parasitol, 44 (2014), pp. 695-708
[23]
S.A. Sarker,H. Mahmud,L. Davidsson,N.H. Alam,T. Ahmed,N. Alam
Causal relationship of Helicobacter pylori with iron-deficiency anemia or failure of iron supplementation in children
Gastroenterology, 135 (2008), pp. 1534-1542 http://dx.doi.org/10.1053/j.gastro.2008.07.030
[24]
H.S. Ali Habib,H.A. Murad,E.M. Amir,T.F. Halawa
Effect of sequential versus standard Helicobacter pylori eradication therapy on the associated iron deficiency anemia in children
Indian J Pharmacol, 45 (2013), pp. 470-473 http://dx.doi.org/10.4103/0253-7613.117757
[25]
E.H. Nashaat,G.M. Mansour
Helicobacter pylori and anemia with pregnancy
Arch Gynecol Obstet, 289 (2014), pp. 1197-1202 http://dx.doi.org/10.1007/s00404-013-3138-8
[26]
N.A. Kotb,M.M. Bedewy,H.H. Soliman,H.M. Nagy,E.A. Hasby
The impact of H. pylori eradication on response to oral iron therapy in patients with iron deficiency anemia
Egypt J Immunol, 19 (2012), pp. 11-18
[27]
W. Xia,X. Zhang,J.J. Wang,C.H. Sun,L.J. Wu
Survey of anaemia and Helicobacter pylori infection in adolescent girls in Suihua, China and enhancement of iron intervention effects by H. pylori eradication
Br J Nutr, 108 (2012), pp. 357-362 http://dx.doi.org/10.1017/S0007114511005666
[28]
R. Malik,K. Guleria,I. Kaur,M. Sikka,G. Radhakrishnan
Effect of Helicobacter pylori eradication therapy in iron deficiency anaemia of pregnancy – a pilot study
Indian J Med Res, 134 (2011), pp. 224-231
[29]
V.M. Cardenas,C.A. Prieto-Jimenez,Z.D. Mulla,J.O. Rivera,D.C. Dominguez,D.Y. Graham
Helicobacter pylori eradication and change in markers of iron stores among non-iron deficient children in El Paso, Texas: an etiologic intervention study
J Pediatr Gastroenterol Nutr, 52 (2011), pp. 326-332 http://dx.doi.org/10.1097/MPG.0b013e3182054123
[30]
G. Vijayan,R.C. Sundaram,Z. Bobby,A. Hamide,N. Selvaraj,N.R. Dasse
Increased plasma malondialdehyde and fructosamine in anemic H. pylori infected patients: effect of treatment
World J Gastroenterol, 13 (2007), pp. 796-800
[31]
L.H. Chen,H.S. Luo
Effects of H. pylori therapy on erythrocytic and iron parameters in iron deficiency anemia patients with H. pylori-positive chronic gastritis
World J Gastroenterol, 13 (2007), pp. 5380-5383
[32]
B.D. Gessner,H.C. Baggett,P.T. Muth,E. Dunaway,B.D. Gold,Z. Feng
A controlled, householdrandomized, open-label trial of the effect that treatment of Helicobacter pylori infection has on iron deficiency in children in rural Alaska
J Infect Dis, 193 (2006), pp. 537-546 http://dx.doi.org/10.1086/499604
[33]
Y.H. Choe,Y.S. Kwon,M.K. Jung,S.K. Kang,T.S. Hwang,Y.C. Hong
Helicobacter pylori-associated iron-deficiency anemia in adolescent female athletes
J Pediatr, 139 (2001), pp. 100-104 http://dx.doi.org/10.1067/mpd.2001.114700
[34]
Y.H. Choe,S.K. Kim,B.K. Son,D.H. Lee,Y.C. Hong,S.H. Pai
Randomized placebo-controlled trial of Helicobacter pylori eradication for iron deficiency anemia in preadolescent children and adolescents
Helicobacter, 4 (1999), pp. 135-139
Copyright © 2018. Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular
Idiomas
Hematology, Transfusion and Cell Therapy

Subscribe to our Newsletter

Article options
Tools
en pt
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.