Observational Study Medicine ®

OPEN

Pediatric gastritis and its impact on hematologic

parameters
∗
Maria Oana Săsăran, MD, PhDa, Lorena Elena Meliţ, MD, PhDb, , Simona Mocan, MDc,
Dana Valentina Ghiga, MD, PhDd, Ecaterina Daniela Dobru, MD, PhDe

Abstract
Non-invasive biomarkers, such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, may predict inflammation in various
disorders, including gastritis, according to recent data. Nevertheless, various studies reported an association between Helicobacter
pylori (H pylori) and immune thrombocytopenia in both adults and pediatric patients. The objective of our study was to evaluate the
impact of pediatric gastritis, caused or not by H pylori infection on erythrocytes, their parameters, thrombocytes, mean platelet
volume, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).
We performed a prospective, case–control study on 151 patients aged between 1 and 17 years who presented with chronic
dyspeptic symptoms. An upper digestive endoscopy with gastric biopsies and a complete blood count was performed in each case.
Control group consisted of 67 patients with normal histological findings, while the two study groups were divided into group 1—H
pylori-induced gastritis (31 patients) and group 2—non-H pylori-induced gastritis (53 patients). Children from the rural area were
more likely to develop both types of gastritis (P < .01). No significant difference was found between either of the study groups and
control group in terms of platelets, mean platelet volume, NLR and PLR (P > .05). However, significantly higher values of lymphocytes
were associated with non-H pylori-induced gastritis (P < .01). Comparison of the two study groups did not reflect any significant
differences in terms of hematological parameters. When assessing these constants in relation to gastritis severity, severe gastritis led
to a compelling decrease in hemoglobin (Hb) and hematocrit (Htc) levels. The comparison of parameters between severe, moderate,
and mild gastritis did not reveal any significant results.
Childhood and adolescent gastritis does not produce a significant effect upon platelet counts, their mean volume, PLR or NLR,
according to our study. An important increase in lymphocyte count might predict non-H pylori pediatric gastritis. Moreover, severe
gastritis might result in an important decrease in Hb and Htc levels.
Abbreviations: H pylori = Helicobacter pylori, Hb = hemoglobin, Htc = hematocrit, LMR = lymphocyte- monocyte ratio, MCV =
mean corpuscular volume, MPV = mean platelet volume, NLR = neutrophil to lymphocyte ratio, PLR = platelet to lymphocyte ratio,
RDW = red blood cell distribution width, SD = standard deviation.
Keywords: children, gastritis, Helicobacter pylori, hematologic parameters

1. Introduction which develops after a long-time span of chronic gastric

Chronic dyspeptic symptoms such as abdominal pain, nausea, inflammation.[1,2]
vomiting, or bloating are often suggestive for the diagnosis of Helicobacter pylori (H pylori), one of the most frequent
gastritis and gastropathies among pediatric patients. A prompt bacterial infection among humans, also represents the main
diagnosis of these entities might prevent life-threatening etiologic factors of pediatric gastritis.[3–5] Several studies reported
complications such as peptic ulcer disease or gastric cancer, an association between this pathogen and hematologic disorders,

Editor: Mostafa Sira.

This research was partially supported by the internal research grant of the University of Medicine, Pharmacy, Sciences and Technology ”George Emil Palade” of Târgu
Mureş, Romania, ”The role of genomic and inflammatory markers in the determinism of child’s gastritis” no. 615/11/17.01.2019.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the present study are available from the corresponding author on reasonable request.
a
Department of Pediatric Cardiology, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology from Târgu Mureş, b Department of Pediatrics,
“George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology from Târgu Mureş, c Pathology Department, County Emergency Clinical Hospital of
Târgu Mureş, d Department of Medical Informatics and Biostatistics, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology from Târgu
Mureş, e Department of Internal Medicine VII, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology from Târgu Mureş, Târgu Mureş,
Romania.
∗
Correspondence: Lorena Elena Meliţ, Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureş,
Gheorghe Marinescu street no 38, Târgu Mureş 540136, Romania (e-mail: lory_chimista89@yahoo.com).
Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to
download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
How to cite this article: Săsăran MO, Meliţ LE, Mocan S, Ghiga DV, Dobru ED. Pediatric gastritis and its impact on hematologic parameters. Medicine 2020;99:35
(e21985).
Received: 29 December 2019 / Received in final form: 7 July 2020 / Accepted: 24 July 2020
http://dx.doi.org/10.1097/MD.0000000000021985

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Săsăran et al. Medicine (2020) 99:35 Medicine

including immune thrombocytopenia.[6] Recent literature data Pediatric Tertiary Hospital from Romania. Patients with chronic
support the screening for H pylori infection in patients with dyspeptic symptoms, such as abdominal pain, bloating, nausea,
idiopathic thrombocytopenic purpura, independently of the vomiting, or pyrosis were included in the study, between
presence of gastrointestinal symptoms.[7–9] An improvement of February 2018 and October 2019. The exclusion criteria were:
the number of platelets has been underlined after successful patients with known chronic illnesses (including previously
eradication of this bacteria.[10] Still, this positive therapeutic known hematologic disorders: immune thrombocytopenic pur-
response seems to be related to the pathogenicity of H pylori pura, acute lymphoblastic or myeloblastic leukemia, lymphoma,
strains, especially the expression of CagA proteins, and therefore autoimmune hemolytic anemia, minor or major thalassemia),
to the geographic variability of the infection severity. Hence, chronic medication which might alter the hematologic param-
Eastern Asian populations diagnosed with thrombocytopenia eters, symptoms of other infectious diseases, parasitic infections
were more likely proved to experience a benefic response after the or weight under 12 kg (due to the characteristics of the video
eradication of H pylori infection.[9] endoscope). The subjects were divided into three groups,
In patients with H pylori positive gastritis, a useful tool for depending on the histopathological findings of the gastric
predicting a possible thrombocyte destruction is the assessment of biopsies:
platelet indexes. Thus, mean platelet volume (MPV) values were
1. group 1—H pylori gastritis,
shown to be higher in patients diagnosed with this type of
2. group 2—non-H pylori gastritis, and
gastritis, as compared to patients without histopathological
3. group 3—control group, consisting of patients without any
evidence of H pylori.[11] This phenomenon might be explained by
pathological changes.
an ongoing process of platelet destruction, initially compensated
by a continuous release of platelet precursor cells with an Laboratory tests included a complete blood count
increased cellular volume into the blood flow.[11,12] performed by an automated hematology analyzer (Cobas Integra
Red blood cell parameters have also been evaluated in 400 plus automated analyzer, Roche Diagnostics GmbH,
correlation with digestive disorders. Therefore, increased red Mannheim, Germany), which revealed absolute values of
blood cell volume distribution width (RDW) seems to be a erythrocytes, platelets, leukocytes, and the entire leukocyte
predictive marker of different gastropathies, including gastric formula, as well as platelet and erythrocyte indices, including
cancer, gastric ulcer, and chronic gastritis.[13]H pylori has been MPV, Hb, Htc, MCV, and RDW. The PLR and NLR values were
shown to produce the same effect upon RDW, whereas lower calculate by dividing platelet/neutrophil count to lymphocyte
values of the hematocrit (Htc), hemoglobin (Hb), and erythrocyte count.
count have been associated with its presence in adults. However, An abdominal ultrasound was performed for each patient, but
these changes seem to be reversible after H pylori eradication, due no abnormalities were found. Moreover, in order to elucidate the
to an improvement in serum iron and vitamin B12 levels.[14] A etiology of the symptoms, a parasitology stool examination was
special attention has been given to iron refractory iron-deficiency recommended in every patients with complaints suggesting a
anemia (IRIDA) in the past years, as H pylori infection parasitic infestation, such as abdominal pain, distension,
eradication has been proved to improve the efficacy of iron flatulence, diarrhea, lack of appetite, or perianal pruritus.[19]
supplementation in various pediatric studies evolving around this As functional abdominal pain and dyspepsia could have
condition. Still, a recent review that summarized the findings of represented the cause of dyspeptic symptoms in certain cases,
multiple studies and randomized control trials on this matter, only patients with a family history of digestive disorders or with
underlined the need for higher quality, larger cohort researches to alarming symptoms were included in the study. Therefore, the
elucidate a possible association between iron deficiency anemia decision of performing an upper digestive endoscopy was based
and H pylori infection in children.[15] upon negative abdominal ultrasound and parasitology stool
Novel inflammatory biomarkers, including neutrophil-to- examination (where applicable), positive family history of
lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio inflammatory bowel disease, celiac disease, peptic ulcer disease
(PLR), have been used as non-invasive predictors for systemic or H pylori infection and the presence of alarming symptoms, in
inflammation in various conditions, including gastritis.[3,16–18] accordance to the latest Rome IV criteria[20]: dysphagia,
Both parameters were assessed so far only in association with H odynophagia, persistent vomiting, hematemesis, melena, invol-
pylori positive gastritis and the role of PLR has been reported so untary weight loss, delayed puberty, lack of appetite, symptoms
far only in adults. Thus, a higher PLR has been described due to persisting for more than 6 months, severe symptoms affecting
an increase in thrombocyte count and a decrease in lymphocyte daily activities, including sleep. Each patient underwent an upper
one.[3] Interestingly, these findings are controversial since digestive endoscopy with gastric biopsies (at least two samples
previous studies stated that H pylori is associated with taken from the antrum and at least two from the corpus[21]) and a
thrombocytopenia. complete blood count. The upper digestive endoscopy was
This study aimed to assess the impact of pediatric gastric performed after a fastening period of at least 10 h, with each
inflammation on the levels of erythrocytes, thrombocytes, Hb, patient benefiting from a mild sedation with Diazepam,
Htc, mean corpuscular volume (MCV), RDW, MPV, NLR, and approximately 20 min prior to the procedure. All upper digestive
PLR. Moreover, our intention was to identify if the changes in endoscopies were performed by a single person using an Olympus
these parameters depend on the presence of H pylori infection, or gastroscope GIF P30. A microscopic examination was conducted
they are related only to the gastric inflammation. in each case, with the help of Giemsa staining, used for identifying
H pylori. The severity of gastritis was assessed in concordance
with the modified, updated Sydney classification system, depend-
2. Materials and methods
ing on the inflammatory modifications, activity, presence of
This prospective study was conducted on a sample of 151 atrophy, intestinal metaplasia and H pylori colonization, as
children aged between 1 and 17 years, who were admitted in a described microscopically.[22,23]

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2.1. Ethics (marked with an asterisk in the result table). The significance
The research was approved by the Ethics Committee of the threshold of the P-value was .05 (a confidence interval of 95%).
University of Medicine, Pharmacy, Science and Technology
“George Emil Palade” of Târgu Mureş (No 64/2018), respecting 3. Results
the principles of the declaration of Helsinki. Prior to admission in 3.1. Study sample design
the study, one of the parents or tutors of the child had to sign an
inform consent. We did not include in the study patients whose Out of the 151 patients enrolled in the study, 67 did not present
legal guardians refused the participation. any microscopical modifications of the gastric mucosa, being
included in control group, 31 were confirmed with H pylori
gastritis—group 1, while 53 were histologically identified with
2.2. Statistical analysis gastritis of other etiologies—group 2 (non-steroid anti-inflam-
For the statistical analysis, the GraphPad PrismT software was matory drug consumption, prolonged proton pump inhibitor
used. Descriptive statistics was helpful in calculating means and intake, biliary reflux or formerly known H pylori infection). The
medians of age and paraclinical data of the patients. For each following histopathological diagnoses were reported in group 2:
series of quantitative variables Shapiro–Wilk normality test was reactive gastropathy (50.9%), focal acute gastritis (32%), and
applied. Depending on its results, the comparison of means and chronic, inactive gastritis (16.9%). The distribution of the study
medians was performed by applying two tests used for unpaired groups and subgroups was described in Figure 1. As atrophy or
data: t test for values complying to a Gaussian distribution and intestinal metaplasia were not identified in either of these cases,
Mann–Whitney test for values sampled from non-Gaussian severity of gastritis was evaluated depending on the extent and
distributions. The use of the later test was marked in the results type of cellular infiltrate of the mucosa. Therefore, intensity of
tables with asterisk, whereas for the unmarked one t test was lymphoplasmocytic infiltrates, amount of lymphoid aggregates
used. Chi square test was used to analyze contingency tables, for (appreciative of chronic inflammation degree) and density of
assessing the relationship between qualitative variables (sex, neutrophils were the criteria used for dividing the subjects into
rural/urban background, symptoms) and the risk of developing four subgroups in terms of severity: no pathological findings,
either type of gastritis (H pylori and non-H pylori gastritis). The mild, moderate, and severe gastritis. Thus, out of the 84 children
analysis of mean parameter differences between multiple groups diagnosed with gastritis, almost half of them (40 subjects—
was done with the help of analysis of variance (ANOVA) test. 47.6%) suffered from a mild form, 26 (30.95%) with moderate
Furthermore, for multiple mean comparison parametric Bonfer- forms and only 18 patients (21.42%) had a severe type of
roni test or non-parametric Kruskal–Wallis test were used gastritis.

Figure 1. Flowchart with the distribution of the study groups and subgroups.

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Table 1
Demographic characteristics and main symptoms of the three groups.
Helicobacter pylori gastritis (n = 31) Non-H pylori gastritis (n = 53) Control group (n = 67) P
Age (years)
Mean ± SD 12.68 ± 3.55 11.35 ± 4.17 12.11 ± 3.22 .321
Sex (n)
Female 19 31 31 .259
Male 12 22 36
Background (n)
Rural 27 33 26 <.001
Urban 4 20 41
Abdominal pain (n)
Yes 29 44 53 .200
No 2 9 14
Nausea (n)
Yes 14 16 12 .017
No 17 37 55
Vomiting (n)
Yes 10 13 10 .130
No 21 40 57
Weight loss (n)
Yes 1 2 1 .723
No 30 51 66
n = number, SD = standard deviation.
The bold significance are used for highlighting statistically significant values (P < .05).

3.2. Demographic characteristics and main symptoms 3.3. Analysis of hematological parameters
The demographic characteristics of the children included in our We analyzed the variations of hematological parameters between
study, as well as the distribution of the main symptoms within the the two study groups and control group, but we also compared
study group and control groups were mentioned in Table 1. The their values between children with H pylori and non-H pylori
mean age was 12.11 ± 3.22 years for the control group, 12.68 ± gastritis, in order to assess the impact of H pylori on these
3.55 years for group 1 and 11.35 ± 4.17 for group 2, without parameters (Tables 2 and 3). Mean platelet, leukocyte, and MPV
significant differences in terms of age (P = .321), or gender values were higher in patients with both forms of gastritis, but did
distribution (P = .259). However, children from rural areas not differ significantly from the control group (P > .05). In spite of
(56.95%) were more likely to be diagnosed with gastritis the increased lymphocyte count in both study groups as
(P < .01). The most common chronic symptoms encountered in compared to control group, the mean values of the lymphocytes
our study indicating an upper digestive endoscopy were: were associated with non-H pylori gastritis (P = .007), but not
abdominal pain (83.44%), nausea (27.81%), vomiting with H pylori gastritis (P = .541). An increase of both PLR and
(21.85%), heartburn (14.56%), loss of appetite (5.96%), and NLR was noticed in H pylori induced gastritis, while a decrease
regurgitations (1.98%), but nausea was the only symptom of these parameters was found in children with non-H pylori
significantly associated with gastritis (P = .0177). gastritis, both without statistical significance (P = .904/P = .867).

Table 2
Comparison of hematologic parameters between non-Helicobacter pylori gastritis and control groups.
Non-H pylori gastritis (n = 53) Control group (n = 67)
Parameter Mean ± SD (median) Mean ± SD (median) P
∗
PLR 131.9 ± 66.77 (111.4) 140.3 ± 53.96 (126.5) .076
∗
NLR 1.75 ± 1.212 (1.45) 1.96 ± 1.28 (1.66) .258
∗
MPV (fL) 10.22 ± 1.07 (10.30) 9.86 ± 1.10 (10.00) .114
Platelets (number/mL) 309,815 ± 94,462 (307,000) 301,103 ± 71,209 (294,000) .578
∗
Leukocytes (number/mL) 7767 ± 2180 (7790) 7270 ± 1852 (6915) .192
∗
Neutrophils (number/mL) 4077 ± 1494 (3870) 4158 ± 1815 (3830) .864
∗
Lymphocytes (number/mL) 2751 ± 1120 (2610) 2268 ± 608.9 (2310) .007
∗
Erythrocytes (x106/mL) 4.77 ± 0.422 (4.82) 4.86 ± 0.432 (4.86) .415
∗
Hb (g/dL) 13.25 ± 1.17 (13.40) 13.46 ± 1.41 (13.50) .460
∗
Htc % 38.72 ± 3.23 (39.20) 39.54 ± 3.59 (39.40) .291
∗
MCV (fL) 81.27 ± 4.70 (80.50) 81.28 ± 3.56 (81.30) .641
∗
RDW % 13.59 ± 1.37 (13.30) 13.35 ± 1.59 (13.20) .326
Hb = hemoglobin, Htc = hematocrit, MCV = mean cellular volume, MPV = mean platelet volume, n = number, NLR = neutrophil-to-lymphocyte ratio, PLR = platelet-to-lymphocyte ratio, SD = standard deviation.
∗
Mann–Whitney test was used.
The bold significance are used for highlighting statistically significant values (P < .05).

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Table 3
Comparison of hematologic parameters between the Helicobacter pylori gastritis and control groups.
H pylori gastritis (n = 31) Control group (n = 67)
Parameter Mean ± SD (median) Mean ± SD (median) P
∗
PLR 144.6 ± 57.85 (119.1) 140.3 ± 53.96 (126.5) .904
∗
NLR 2.05 ± 1.53 (1.34) 1.96 ± 1.28 (1.66) .867
∗
MPV (fL) 10.02 ± 0.98 (10.00) 9.86 ± 1.10 (10.00) .860
Platelets (number/mL) 311,032 ± 81,816 (288,000) 301,103 ± 71,209 (294,000) .542
∗
Leukocytes (number/mL) 7370 ± 1910 (6780) 7270 ± 1852 (6915) .747
∗
Neutrophils (number/mL) 3923 ± 1747 (3450) 4158 ± 1815 (3830) .533
Lymphocytes (number/mL) 2358 ± 806.1 (2270) 2268 ± 608.9 (2310) .541
Erythrocytes (106/mL) 4.68 ± 0.38 (4.66) 4.86 ± 0.43 (4.86) .049
∗
Hb (g/dL) 12.86 ± 1.71 (13.20) 13.46 ± 1.41 (13.50) .107
∗
Htc % 37.75 ± 4.30 (38.70) 39.54 ± 3.59 (39.40) .109
∗
MCV (fL) 81.25 ± 6.63 (82.40) 81.28 ± 3.56 (81.30) .627
∗
RDW % 13.66 ± 2.00 (13.30) 13.35 ± 1.59 (13.20) .742
Hb = hemoglobin, Htc = hematocrit, MCV = mean cellular volume, MPV = mean platelet volume, n = number, NLR = neutrophil-to-lymphocyte ratio, PLR = platelet-to-lymphocyte ratio, RDW = red cell distribution
width, SD = standard deviation.
∗
Mann–Whitney test was used.
The bold significance are used for highlighting statistically significant values (P < .05).

Mean Hb, Htc, and MCV values were lower in the two study and patchy hemorrhages. In terms of hematological parameters,
groups in comparison to control one (P > .05). Mean erythrocyte no significant findings were revealed.
values were the only ones that were found to be significantly
decreased in H pylori gastritis group as opposed to healthy
3.5. Hematological parameters and gastritis severity
children (P = .049). In term of erythrocyte indices, RDW
presented higher mean percentages in both study groups, but Assessing the relationship between hematological parameters and
without statistical significance. gastritis severity degrees, we noticed that Hb and Htc values were
Table 4 describes the results of each mean comparison significantly lower in children with severe gastritis as compared to
performed between group 1 and group 2, showing that studied those included in control group (12.68 ± 1.43 vs 13.46 ± 1.41 in
complete blood count parameters and novel proposed inflam- control group, P = .041/37.03 ± 4.07 vs 39.54 ± 3.59, P = .023)
matory biomarkers, NLR, and PLR, are not influenced by the sole (Table 5). Nevertheless, no significant differences were found in
presence of H pylori infection in the context of gastric terms of hematological parameters between children with mild,
inflammation. moderate, or severe gastritis (Table 6).

3.4. Macroscopic findings 4. Discussions

Assessing the endoscopic findings, we noticed that macroscopic Prevalence of H pylori has decreased in recent years, but it still
cobblestone aspect was significantly more frequent in patients remains a public health problem in areas with a poor socio-
with H pylori infection (P < .01). Nevertheless, other macro- economic level and in individuals originating from rural
scopic aspects included hyperemia, edema, erosions, friability, environments.[24–26] Our study supports these findings proving

Table 4
Comparison of hematologic parameters between the non-Helicobacter pylori gastritis and H pylori gastritis groups.
H pylori gastritis (n = 31) Non-H pylori gastritis (n = 53)
Parameter mean ± SD (median) mean ± SD (median) P
∗
PLR 144.6 ± 57.85 (119.1) 131.9 ± 66.77 (111.4) .210
∗
NLR 2.05 ± 1.53 (1.34) 1.75 ± 1.21 (1.45) .484
MPV (fL) 10.02 ± 0.98 (10.00) 10.22 ± 1.07 (10.30) .409
Platelets (number/mL) 311,032 ± 81,816 (288,000) 309,815 ± 94,462 (307,000) .952
∗
Leukocytes (number/mL) 7370 ± 1910 (6780) 7756 ± 2161 (7790) .334
∗
Neutrophils (number/mL) 3923 ± 1747 (3450) 4077 ± 1494 (3870) .332
∗
Lymphocytes (number/mL) 2358 ± 806.1 (2270) 2751 ± 1120 (2610) .107
∗
Erythrocytes (106/mL) 4.68 ± 0.38 (4.66) 4.77 ± 0.42 (4.82) .160
∗
Hb (g/dL) 12.86 ± 1.71 (13.20) 13.25 ± 1.17 (13.40) .370
∗
Htc % 37.75 ± 4.30 (38.70) 38.72 ± 3.23 (39.20) .321
∗
MCV (fL) 81.25 ± 6.63 (82.40) 81.27 ± 4.70 (80.50) .486
∗
RDW % 27.54 ± 3.03 (27.90) 27.78 ± 1.67 (27.60) .745
Hb = hemoglobin, Htc = hematocrit, MCV = mean cellular volume, MPV = mean platelet volume, n = number, NLR = neutrophil-to-lymphocyte ratio, PLR = platelet-to-lymphocyte ratio, RDW = red cell distribution
width, SD = standard deviation.
∗
Mann–Whitney test was used.

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Table 5
Comparison of hematologic parameters between the severe forms of gastritis and control group.
Gastritis-severe form (n = 18) Control group (n = 67)
Parameter Mean ± SD, (Median) Mean ± SD, (Median) P
∗
PLR 144.7 ± 61.91 (121.5) 140.3 ± 53.96 (126.5) .874
∗
NLR 2.08 ± 1.59 (1.37) 1.96 ± 1.28 (1.66) .857
∗
MPV (fL) 10.21 ± 1.01 (10.00) 9.86 ± 1.10 (10.00) .330
Platelets (number/mL) 299,833 ± 72,066 (276,000) 301,103 ± 71,209 (294,000) .946
∗
Leukocytes (number/mL) 7440 ± 1905 (7030) 7279 ± 224 (6940) .759
∗
Neutrophils (number/mL) 4033 ± 1698 (3485) 4158 ± 1815 (3830) .814
Lymphocytes (number/mL) 2318 ± 926.6 (2285) 2268 ± 608.9 (2310) .828
Erythrocytes (106/mL) 4.66 ± 0.38 (4.67) 4.86 ± 0.43 (4.86) .080
Hb (g/dL) 12.68 ± 1.43 (12.95) 13.46 ± 1.41 (13.50) .041
∗
Htc % 37.03 ± 4.07 (38.45) 39.54 ± 3.59 (39.40) .023
MCV (fL) 80.42 ± 4.88 (81.05) 81.28 ± 3.56 (81.30) .401
∗
RDW % 13.68 ± 1.45 (13.30) 13.35 ± 1.59 (13.20) .404
Hb = hemoglobin, Htc = hematocrit, MCV = mean cellular volume, MPV = mean platelet volume, n = number, NLR = neutrophil-to-lymphocyte ratio, PLR = platelet-to-lymphocyte ratio, RDW = red cell distribution
width, SD = standard deviation.
∗
Mann–Whitney test was used.
The bold significance are used for highlighting statistically significant values (P < .05).

a positive correlation between rural area and children H pylori- tal investigation was carried out on mice, which analyzed platelet
induced gastritis. Moreover, an overall higher incidence of counts two months after H pylori inoculation of three different
gastritis was found in children from rural areas. strains a decrease in platelet count being documented in only one
H pylori infection seems to be less aggressive on children’s of the strains. Thus, this experimental study incriminated the
gastric mucosa as opposed to adults, due to a boost in regulation variability of the major histocompatibility complex as the most-
of T cell activity, typical for this age.[27] However, it produces a likely factor responsible for thrombocytopenia and not the
systemic response, mediated by pro-inflammatory cytokines, antibodies directed against H pylori.[33] Nevertheless, there are
causing systemic manifestations, even in pediatric patients.[28,29] few data regarding a possible association between H pylori and
Its oncoprotein CagA has been associated with both carcinogen- thrombocytopenia in children. These studies involved a small
esis[30] and hematologic disorders, including thrombocytope- number of patients, and described a partial or significant increase
nia.[31] Due to its molecular mimicry, this protein can cross-react in platelet count only in selected cases after eradication of H
with platelet-associated immunoglobulin G antibodies, therefore pylori.[34,35] Moreover, one of the few studies in the literature
triggering autoimmune-induced destruction of platelets.[31] This that compared MPV and platelet values in pediatric patients
finding remains controversial since other mechanisms, such as found a weak relationship between confirmed gastritis, regardless
phagocytic activity of monocytes, have also been reported as a of severity, or H pylori infection and a mild decrease in
potential mechanism.[9] Hence, further studies are necessary for thrombocyte count. Still, MPV did not present any significant
the elucidation of the exact molecular pathways. changes in any of the studied groups.[12] Similarly, our study did
Various adult studies have underlined the role of H pylori not find any important changes in MPV values in children with
infection in the development of immune thrombocytopenia.[32] gastritis independently of the etiology, and failed in identifying a
Thus, due to consistent data proving an association between H possible correlation between this parameter and gastritis severity
pylori and idiopathic thrombocytopenic purpura, an experimen- degrees. However, in terms of platelet count, the present study

Table 6
Comparison of hematologic parameters between different grades of gastritis severity.
Mild gastritis (n = 40) Moderate gastritis (n = 26) Severe gastritis (n = 18)
Parameter Mean ± SD (median) Mean ± SD (median) Mean ± SD (median) P
∗
PLR 131.3 ± 61.18 (120.8) 139.2 ± 69.79 (111.9) 144.7 ± 61.91 (121.5) .742
∗
NLR 1.654 ± 0.91 (1.43) 2.040 ± 1.66 (1.41) 2.08 ± 1.59 (1.37) .752
MPV (fL) 10.29 ± 0.98 (10.34) 9.878 ± 1.117 (9.90) 10.21 ± 1.01 (10.00) .280
Platelets (number/mL) 301,185 ± 89,661 (298,000) 325,577 ± 97,803 (335,500) 299,833 ± 72,066 (276,000) .570
∗
Leukocytes (number/mL) 7569 ± 1788 (7715) 7812 ± 2613 (7320) 7441 ± 1905 (7030) .939
Neutrophils (number/mL) 3953 ± 1503 (3695) 4115 ± 1681 (3855) 4033 ± 1698 (3485) .921
∗
Lymphocytes (number/mL) 2673 ± 972.8 (2545) 2702 ± 1172 (2675) 2318 ± 926.6 (2285) .397
∗
Erythrocytes (106/mL) 4.77 ± 0.42 (4.80) 4.74 ± 0.41 (4.70) 4.66 ± 0.38 (4.67) .600
∗
Hb (g/dL) 13.34 ± 1.08 (13.45) 13.04 ± 1.75 (13.35) 12.68 ± 1.43 (12.95) .115
∗
Htc % 39.04 ± 3.02 (39.54) 38.23 ± 4.13 (39.00) 37.03 ± 4.07 (38.45) .089
∗
MCV (fL) 81.96 ± 4.40 (81.00) 80.77 ± 7.13 (81.00) 80.42 ± 4.88 (81.05) .789
∗
RDW % 13.25 ± 0.91 (13.20) 14.16 ± 2.34 (13.35) 13.68 ± 1.45 (13.30) .466
Hb = hemoglobin, Htc = hematocrit, MCV = mean cellular volume, MPV = mean platelet volume, n = number, NLR = neutrophil-to-lymphocyte ratio, PLR = platelet-to-lymphocyte ratio, SD = standard deviation.
∗
Kruskal–Wallis test was used.

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reveals that the presence of mild and moderate gastritis might authors stated that reference values for these biomarkers depend
results in a slight increase in this hematological parameter. also on race and therefore further studies should be conducted in
Contrariwise, in case of children with severe gastritis, we found a larger geographic areas.[42]
decrease in platelet count. Nevertheless, none of these results It is well-documented that iron deficiency and vitamin B12
were found to be statistically significant. A possible hypothesis deficiency anemia is associated with H pylori infection.
for these findings might be related to a compensatory mechanism According to a Palestinian study, this infections results in a
expressed in the early stages of gastritis stimulating initially the decrease of mean erythrocytes, Hb and Htc levels, and a decrease
production of thrombocytes. However, in patients diagnosed of RDW.[14] Moreover, eradication of the infection seems to be
with H pylori gastritis higher MPV values were found as followed by a significant improvement in serum iron and vitamin
compared to those with gastritis of other etiologies or control B12 levels, even without supplementation.[43] Nevertheless, few
group, but without statistical significance. data describe the influence of H pylori on erythrocytes and their
Recent studies focused on assessing the usefulness of complete indexes. Thus, the study of Li et al underlined a significant
blood count parameters as a tool in gastric cancer screening.[36] increase in RDW related to chronic gastritis.[13] Similarly, our
Platelets appear to be involved in promoting carcinogenesis, by study revealed an association between H pylori gastritis and
increasing the secretion of pro-inflammatory cytokines.[37] lower erythrocyte values. However, hematologic parameters
Contrariwise, lymphocyte proliferation is considered a protective were not significantly different in severe forms, when compared
factor against tumor growth.[36] It is important to note that in our to moderate or mild ones.
research lymphocyte counts were significantly higher in patients Our control group included children with no microscopic
with non-H pylori gastritis in comparison to healthy controls and pathologic findings who were most-likely suffering from
H pylori gastritis. As it is well known that H pylori expresses a functional abdominal pain or dyspepsia taking into account
carcinogenic potential,[38] lack of relevant proliferation of the Rome IV criteria. Although Rome IV criteria does not support
lymphocytes in patients from group 1 might suggest a possible performing an upper digestive endoscopy in these cases, the
long-term malignant transformation. PLR and NLR were proven authors of the recent guideline recognize its need in patients with
to be reliable inflammatory markers for the diagnosis and staging alarming symptoms and the fact that this invasive maneuver
of gastric cancer, whether used individually or in combina- cannot be avoided in all cases.[20] Thus, according to the most
tion.[39] In terms of H pylori induced gastritis, the high values of recent Rome IV criteria we considered appropriate to perform an
these two biomarkers is caused by an increase in thrombocyte or upper digestive endoscopy in these patients as well, since their
neutrophil counts and a decrease in lymphocyte one.[3,40] symptoms or family history matched with their recommenda-
Contrariwise, our research showed an increase in mean values tions.
of PLR and NLR in children with H pylori-induced gastritis and a Probably one of the major limitations of this study consists in
decrease of these values in those with H pylori-negative gastritis, the relatively small sample size, and the reduced number of
but without statistical significance. No significant differences patients with H pylori-induced gastritis. Moreover, it would have
were noted when comparing these biomarkers or other been important to assess the hematological parameters depending
hematologic parameters including leukocyte count between the on different age groups, but we intend to expand our sample in
two study groups, nor in relation with gastritis severity degrees. the future and to accomplish this objective as well. Another
The only study so far that investigated the modification of NLR potential limitation consists in the fact that the study was
values in children with H pylori gastritis proved a mild increase of performed in a single medical unit, and thus we were not able to
this marker in these patients as compared to control group, but assess the role of geographic area and ethnicity on these results.
without significant differences, similarly to our findings.[16] The Furthermore, as all of the patients included in the study presented
same study underlined a significant increase in both neutrophil gastro-intestinal symptoms and underwent an upper digestive
and lymphocyte counts in children with H pylori positive gastritis endoscopy, this study did not include any asymptomatic H pylori
as opposed to ours, in which neutrophils did not differ children, which would have constituted a valuable study group,
significantly between the three groups included in our study.[16] ruling out a potential source of bias. Severity of gastritis was
Furthermore, a research conducted on adult patients reported a assessed according to the Sydney classification system, but only
significant association between the severity of H pylori positive by taking into account inflammation and activity and not severity
gastritis and both elevated white blood cells and NLR values of H pylori infection. As the sample of subjects with H pylori
explained by an increase in neutrophil count and a decrease in infection was small, dividing this population into three groups
lymphocyte one. However, the authors underlined the reversibil- and comparing each of them with patients without H pylori
ity of this elevated ratio after eradication therapy.[40] Thus, infection would have led to unreliable, bias prone statistic results.
multiple previously mentioned focused mainly on the impact of Several strengths of our study are worth mentioning. Therefore,
symptomatic or asymptomatic H pylori infection on hematologic to the best of our knowledge, it is the first one that assessed the
parameters.[16,38–40] It is important however to take into effect of childhood and adolescent H pylori and non-H pylori
consideration that few literature data have provided reference gastritis, as well as their severity on erythrocyte, platelet,
values for these novel inflammatory markers.[41] A recent study lymphocyte, PLR, NLR, Hb, Htc, MCV, RDW, and MPV
conducted on a large adult South Korean healthy population values. Additionally, it is among the few studies that established
tried to establish reference values for NLR, PLR, MPV, and the diagnosis of H pylori positive gastritis based on gastric biopsy
lymphocyte/monocyte ratio (LMR). These reference intervals exam since most of the findings reported in the literature were not
were divided based on age and gender.[42] Taking into account based on upper digestive endoscopy. Further studies on larger
the previously mentioned reference values, we could mention that pediatric populations, including asymptomatic H pylori patients
the mean values NLR, PLR, and MPV obtained in our study were as well would be useful extremely useful for providing clearer
similar to those reported in the study of Monzón et al, PLR and conclusions, as well as the assessment of the long-term effect of H
NLR values were higher in our control group. However, the pylori eradication upon hematological parameters.

7
Săsăran et al. Medicine (2020) 99:35 Medicine

5. Conclusions [11] Umit H, Umit EG. Helicobacter pylori and mean platelet volume: a
relation way before immune thrombocytopenia? Eur Rev Med
H pylori, one of the most common infections worldwide might Pharmacol Sci 2015;19:2818–23.
express a systemic impact being related to variations in [12] Agin M, Kayar Y, Dertli R. The relationship between mean platelet
hematological parameters. Our study proved that children with volume and platelet levels of children with Helicobacter pylori and
gastritis. Prz Gastroenterol 2019;14:198–201.
H pylori positive gastritis presented a mild increase in both NLR [13] Li T, Huang A, Zhang M, et al. Increased red blood cell volume
and PLR, while these markers were found to have lower values in distribution width: important clinical implications in predicting gastric
non-H pylori gastritis. Despite the lack of statistical significance, diseases. Clin Lab 2017;63:1199–206.
these findings might suggest that H pylori infection might own the [14] Mwafy SN, Afana WM. Hematological parameters, serum iron and
vitamin B12 levels in hospitalized Palestinian adult patients infected with
main role in the impairment of these parameters. Moreover,
Helicobacter pylori: a case-control study. Hematol Transfus Cell Ther
lymphocyte count might be an important predictor of non-H 2018;40:160–5.
pylori gastritis since higher values were noticed in this group. [15] Gheibi S, Farrokh-Eslamlou HR, Noroozi M, et al. Refractory iron
Gastritis severity is an important trigger of anemia in pediatric deficiency anemia and Helicobacter pylori Infection in pediatrics: a
patients with gastritis independently of H pylori infection taking review. Iran J Ped Hematol Oncol 2015;5:50–64.
[16] Meliţ LE, Mărginean MO, Mocan S, et al. The usefulness of
into account that our study revealed significantly lower Hb and inflammatory biomarkers in diagnosing child and adolescent’s gastritis.
Htc levels in children with severe form of gastritis. Further studies Medicine [Internet] 2019;98: Available at: https://www.ncbi.nlm.nih.
are required on larger samples involving also the effect of H gov/pmc/articles/PMC6616319/.
pylori eradication on hematological parameters in order to [17] Ma?rginean CO, Ma?rginean C, Meliţ LE. New insights regarding
genetic aspects of childhood obesity: a minireview. Front Pediatr
establish accurately the relationship between this infection and
2018;6:271.
systemic inflammation, as well as long-term malignant transfor- [18] Mărginean C, Meliţ L, Ghiga D, et al. Early inflammatory status related
mation. to pediatric obesity (STROBE compliant article). Front Pediatr
2019;7:241.
[19] Genta RM. Diarrhea in helminthic infections. Clin Infect Dis 1993;16
Author contributions
(Suppl 2):S122–129.
Conceptualization: Maria Oana Săsăran. [20] Hyams JS, Di Lorenzo C, Saps M, et al. Functional disorders:
children and adolescents. Gastroenterology 2016;doi: 10.1053/j.gas-
Data curation: Maria Oana Săsăran.
tro.2016.02.015.
Formal analysis: Maria Oana Săsăran, Lorena Elena Meliţ , Dana [21] Jones NL, Koletzko S, Goodman K, et al. Joint ESPGHAN/NASPGHAN
Valentina Ghiga. guidelines for the management of Helicobacter pylori in children and
Investigation: Maria Oana Săsăran, Lorena Elena Meliţ , Simona adolescents (update 2016). J Pediatr Gastroenterol Nutr 2017;64:991–
Mocan. 1003.
[22] Price AB. The Sydney system: histological division. J Gastroenterol
Methodology: Maria Oana Săsăran. Hepatol 1991;6:209–22.
Software: Dana Valentina Ghiga. [23] Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of
Supervision: Maria Oana Săsăran. gastritis. The updated Sydney System International Workshop on the
Validation: Maria Oana Săsăran. histopathology of gastritis, Houston 1994. Am J Surg Pathol
1996;20:1161–81.
Visualization: Maria Oana Săsăran.
[24] Bálint L, Tiszai A, Kozák G, et al. Epidemiologic characteristics of
Writing – original draft: Maria Oana Săsăran. Helicobacter pylori infection in southeast Hungary. World J Gastro-
Writing – review & editing: Maria Oana Săsăran. enterol 2019;25:6365–72.
[25] Awuku YA, Simpong DL, Alhassan IK, et al. Prevalence of helicobacter
pylori infection among children living in a rural setting in Sub-Saharan
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