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СпутникиРНSpaceXРоскосмосNASABackground and Objectives Helicobacter pylori is a known Gram-negative bacterium that colonizes the stomach of about 50% of the global population. Besides causing gastrointestinal symptoms, such as abdominal pain, discomfort, nausea, and burping, it also affects various other parts of the body, including the hematological system. Therefore, this retrospective cross-sectional study aimed to investigate complete blood count (CBC) parameters among patients infected with H. pylori. Materials and Methods This study was conducted at the polyclinic of King Faisal University in Al-Ahsa, Saudi Arabia. The data were collected between February and September 2024 from electronic medical records for 2015 to 2022. The 152 patients identified were split equally into two groups based on their H. pylori stool antigen test results: 76 with positive results, and 76 with negative results. Results CBC parameters did not differ significantly between groups. However, some CBC parameters differed significantly between males and females: hemoglobin, hematocrit, and red blood cell counts were significantly higher in males in both groups (both p
Helicobacter pylori is a known Gram-negative bacterium1 that has been classified as a class 1 carcinogen by both the World Health Organization (WHO) in 1994 and the International Agency for Research on Cancer.2–4 This classification reflects its well-established role in gastric carcinogenesis, as H. pylori infection can cause peptic ulcers, chronic gastritis, and gastric cancer,5 and its colonization of the stomach of about 50% of the global population.6
H. pylori infection mostly occurs during childhood, leading to a carrier state that may subsequently manifest symptoms in adulthood. However, most individuals infected with H. pylori are asymptomatic or show atypical or unclear symptoms.7 The most common symptoms of H. pylori infection are abdominal pain and discomfort, nausea, burping, and loss of appetite. Additional reported symptoms include weight loss, bloating, heartburn, and excessive burping.8 According to available data, 85%–95% of individuals in developing countries are infected with H. pylori, compared with approximately 30%–50% in developed countries.9–11
Although several epidemiological studies have reported risk factors for H. pylori infection, the exact mechanism of infection transmission remains unknown.12 Environmental factors, family living circumstances, and socioeconomic status are among the main risk factors.13 Recommendations now indicate that the initial course of treatment for H. pylori infection is an established triple therapy, comprising a proton pump inhibitor (PPI) and two antibiotics: clarithromycin and amoxicillin/metronidazole.6 However, the global prevalence of antibiotic-resistant H. pylori has reached concerning levels, requiring a rapid search for alternative therapies. A systematic review and meta-analysis of 178 studies revealed that the rate of H. pylori primary and secondary genotypic resistance has increased in six WHO regions.14 One study in Saudi Arabia reported a high prevalence of H. pylori antibiotic resistance, with the highest resistance to metronidazole (48.2%), followed by clarithromycin (27.7%), amoxicillin (14.6%), and tetracycline (9.5%).15
Besides its gastrointestinal effects, H. pylori infection also affects various other parts of the body, including the hematological system.16,17 Previous studies have associated numerous hematological conditions with H. pylori infection, including iron deficiency anemia (IDA), vitamin B12 deficiency, and idiopathic thrombocytopenic purpura (ITP).18,19 In the polyclinic at King Faisal University, anemia is defined as a hemoglobin (Hb) level below 12.5 g/dL, and thrombocytopenia is defined as a platelet count below 150 × 109/L, without specific cutoffs by sex or age. Five randomized controlled trials and one meta-analysis of 15 observational studies have associated H. pylori infection with IDA, with H. pylori eradication non-significantly increasing Hb and serum ferritin levels.20
In addition, studies have demonstrated that anemia is common in individuals with H. pylori–related gastritis and that H. pylori infection is significantly associated with anemia severity,21,22 which commonly presents with microcytic and megaloblastic features.21 One study explained that when iron is absorbed in an acidic gastric environment, ascorbic acid reduces ferric iron to ferrous iron. Pathological changes in inflamed tissue can reduce ascorbic acid levels and gastric acidity, which can lead to IDA. These H. pylori–induced changes may contribute to inadequate iron absorption. Moreover, stomach inflammation, irrespective of its severity, tends to increase the nonfunctional form of ascorbic acid, leading to the same outcome. Additionally, bacteria require iron to thrive, and occasionally, they will even outcompete their host for it. Thus, regardless of its manifestations, H. pylori infection can reduce dietary iron absorption.
Bleeding-related gastritis, blood oozing from peptic ulcers, and malignancies are additional potential causes or aggravating factors of iron deficiency. In vitamin B12 deficiency, it is well known that H. pylori–related gastritis reduces the acid secretion, which is required for the release of protein-bound vitamin B12. In addition, chronic H. pylori infections and PPI use can cause atrophic gastritis, which reduces cobalamin-binding intrinsic factor (CBLIF) synthesis, contributing to vitamin B12 insufficiency.23 A significant proportion of patients with ITP are infected with H. pylori, and mounting evidence indicates that eradicating H. pylori enhances their platelet counts according to a meta-analysis of seven studies in the middle eastern region involving 228 patients.24 The anti-platelet autoantibody reaction is fully resolved in most patients with ITP who respond to H. pylori eradication therapy, with no recurrence for over 7 years, suggesting complete recovery from ITP. Thus, H. pylori infection should be evaluated in adult patients with ITP, and eradication therapy is advised if an infection is detected.25
Several studies have established an association between H. pylori infection and changes in complete blood count (CBC) parameters.26–28 However, Shih et al. reported no significant differences in Hb, ferritin, serum iron, or total iron-binding capacity between H. pylori-infected and uninfected individuals, suggesting no clear association.29 Therefore, this study aimed to investigate CBC parameters among H. pylori-infected and uninfected patients to evaluate their causal associations. It focuses primarily on anemia and thrombocytopenia and secondarily on other CBC indices.
This retrospective cross-sectional study was conducted at the polyclinic of King Faisal University in Al-Ahsa, Saudi Arabia, between February and September 2024. It investigated associations between H. pylori infection and CBC parameters among patients who visited the polyclinic.
The exact population size of patients infected with H. pylori in Al-Ahsa has not been reported. In Saudi Arabia, the reported prevalences have ranged from 70% in 1989 to as low as 10.2% in 2018; therefore, based on a total population of approximately 35 million, the number of individuals infected with H. pylori is estimated to be between 3.5 and 24.5 million.30,31
The minimum sample size required for this study was estimated using OpenEpi (version 3.0, https://www.openepi.com/Menu/OE_Menu.htm).32 Considering 3.5–24.5 million individuals infected with H. pylori in Saudi Arabia, a 95% confidence interval, an anticipated frequency of 50%, and a design effect of 1, the required sample size was estimated to be 385. However, this study included 152 patients from February to September 2024, given time constraints, data collection process, and relevant policies. The electronic medical records of patients who underwent H. pylori testing from 2015 to 2022 at the polyclinic of King Faisal University were screened. Ultimately, this study included 76 patients with positive H. pylori test results and 76 with negative H. pylori test results.
The study cohort comprised 152 randomly selected patients who underwent H. pylori testing between 2015 and 2022 at the polyclinic at King Faisal University, and data were extracted from their electronic medical records between February and September 2024. The positive group comprised 76 patients with a verified diagnosis of H. pylori infection based on a stool antigen test, and the control group comprised 76 patients with negative H. pylori stool antigen test results. The only inclusion criterion was a H. pylori stool antigen test result. There were no specific exclusion criteria, such as chronic diseases (e.g., anemia, sickle cell disease, or other hematological conditions) or age restrictions, because the electronic medical record system used in the polyclinic at King Faisal University cannot separate patients by disease status or age. Thus, such exclusions would require manual review of all relevant electronic medical records, which would take substantial time and effort, making it infeasible. Therefore, this study only considered the H. pylori stool antigen test result when screening patients for inclusion. Thus, the study sample included patients of all ages with and without chronic diseases and/or comorbidities.
The data were collected between February and September 2024. Relevant demographic and clinical data were extracted from the patients’ electronic medical records, including age, sex, and CBC parameters such as Hb, hematocrit (HCT), red blood cell (RBC) count, platelet count, white blood cell count, and differential count. All data were de-identified and securely stored in a database for analysis.
This study was approved by the deanship of scientific research of King Faisal University in Al-Ahsa, Saudi Arabia (Project No. KFU-REC-2023-DEC-ETHICS1782) before its commencement and adhered to local regulations and the ethical principles outlined in the Declaration of Helsinki. Given its retrospective design. The data were collected and stored separately on password-protected, secure servers, and only authorized study workers had access to them. Paper records containing sensitive identifiers were stored in secure file cabinets. The anticipated benefits of this study include highlighting associations between CBC parameters and H. pylori infection and determining their clinical significance. This study posed no potential risks, burdens, or conflicts of interest. The polyclinic where the data were obtained operates under the same institutional ethics framework.
The SPSS program, version 23, was used to conduct the statistical analyses (IBM, Armonk, NY, USA). Proportions and percentages are used to depict categorical variables. Continuous data are expressed as mean and standard deviation (SD) for normally distributed data, and medians and interquartile ranges (IQR) for non-normally distributed data. Cross-tabulation was done between H. pylori status and the two categorical variables (anemia and thrombocytopenia). Statistical significance was tested using a chi-square test to detect any association between the categorical variables, Fisher’s exact test was used when expected cell counts were small. The independent-samples Mann– Whitney U test was used to compare the averages and to detect any association of CBC parameters across variables with two categories (H. pylori positive and H. pylori negative) and gender (male and female). A significance threshold of p < 0.05 was applied.
In total, 152 patients underwent H. pylori stool antigen testing between 2015 and 2022 at the polyclinic of King Faisal University, and their data were extracted from electronic medical records between February and September 2024. They were divided into two equal groups: 76 in the H. pylori–positive group, and 76 in the H. pylori–negative group. Their demographic and clinical characteristics are presented in Table 1. Among participants, 93 (61.2%) were female, and 59 (38.8%) were male. In addition, 32 (21.1%) of the ages in this study were aged 25–34 years, and 16 (10.5%) were aged >55 years, with a mean age of 33.34 ± 16.70 years. Most participants had no chronic diseases (n = 116, 76.3%), although some had comorbidities, including anemia (n = 36, 23.7%), diabetes mellitus (n = 10, 6.6%), hypertension (n = 9, 5.9%), and thrombocytopenia (n = 6, 3.9%).
The reference ranges, medians, and interquartile ranges (IQRs) of the CBC parameters used in the polyclinic at King Faisal University are presented in Table 2: Hb (g/dL), HCT–packed cell volume (PCV, %), RBC count (×106/mm3), mean corpuscular volume (MCV, fL), mean corpuscular Hb (MCH) (pg), mean corpuscular Hb concentration (MCHC, g/dL), red cell distribution width–coefficient of variation (RDW-CV, %), platelet count (×103/mm3), total leucocytic count (×103/mm3), neutrophil count (×109/L), lymphocyte count (×109/L), monocyte count (×109/L), eosinophil count (×109/L), basophil count (×109/L), neutrophil percentage (%), lymphocyte percentage (%), monocyte percentage (%), eosinophil percentage (%), basophil percentage (%), mean platelet volume (MPV, fL), platelet distribution width (PDW, fL), plateletcrit (PCT, %), red cell distribution width–standard deviation (RDW-SD, %), platelet–large cell ratio (P-LCR, fL), and platelet–large cell coefficient (P-LCC, fL).
The associations between H. pylori status (positive vs. negative) and CBC parameters are presented in Table 3. Notably, no significant associations were observed in our study cohort.
The associations between H. pylori status (positive vs. negative) with anemia and thrombocytopenia are presented in Table 4. The prevalence of anemia did not differ significantly between the H. pylori–positive and H. pylori–negative groups (22.4% vs. 25.0%, p = 0.703). Similarly, the prevalence of thrombocytopenia was the same in the H. pylori–positive and H. pylori–negative groups (3.9% vs. 3.9%, p > 0.999).
Sex-based differences in CBC parameters were also examined separately in the H. pylori–positive and H. pylori–negative groups, as well as in the entire study cohort ( Table 5). In the H. pylori–positive group, the median (IQR) was significantly higher in males than in females for Hb (14.55 [1.50] vs. 12.10 [2.10] g/dL, p < 0.001), HCT-PCV (43.45% [3.38] vs. 37.40% [5.50], p < 0.001), and RBC count (5.38 [0.51] vs. 4.69 [0.79] × 106/mm3, p < 0.001). In the H. pylori–negative group, the median (IQR) was significantly higher in males than in females for Hb (14.85 [1.78] vs. 12.70 [2.30] g/dL, p < 0.001), HCT-PCV (45.80% [5.50] vs. 38.30% [4.00], p < 0.001), and RBC count (5.29 [0.73] vs. 4.55 [0.92] × 106/mm3, p < 0.001). In contrast, the median (IQR) was significantly lower in males than in females for platelet count (278.00 [125.00] vs. 310.00 [150.00] × 103/mm3, p < 0.007), neutrophil counts (1.79 [1.28] vs. 2.98 [1.81] × 109/L, p < 0.014), PCT (0.25% [0.10] vs. 0.28% [0.10], p < 0.042), and P–LCC (58.00 [28.00] vs. 75.00 [33.00] fL, p < 0.019). Additionally, the median (IQR) was marginally lower in males than in females for RDW-CV (13.15% [1.57] vs. 13.90% [1.10], p < 0.061) and total leucocytic count (4.89 [1.66] vs. 6.28 [1.80] × 103/mm3, p < 0.060).
H. pylori is one of the most prevalent bacterial infections affecting individuals worldwide. It is responsible for causing gastric inflammation, peptic ulcers, and gastric cancer. According to previous research, H. pylori also has a role in hematological changes, including iron-deficiency anemia, vitamin B12 deficiency, and thrombocytopenia.33 As multiple studies have examined the relationship between hematological changes and H. pylori infection, our study aimed to examine how CBC parameters differed by H. pylori infection status among patients attending the outpatient clinics at King Faisal University.
Our findings revealed no significant difference in most CBC parameters by H. pylori infection status ( Table 3). They are consistent with a similar study conducted at King Abdulaziz University Hospital in Saudi Arabia in 2019, which found no association between H. pylori infection and hematological changes.34 Moreover, a prospective study in Iraq found no notable differences or changes in RBC counts, HCT, MCV, and MCHC between patients infected with H. pylori and uninfected patients.35 However, it did observe significantly lower Hb, RDW-SD, and MCHC among patients infected with H. pylori than among uninfected patients (all p < 0.01), as well as significant differences in lymphocytes, monocytes, and granulocytes. Nonetheless, our findings contradict those of a case-controlled study in Sudan in 2018, which found markedly lower RBCs, Hb, HCT, MCV, and neutrophil counts among patients infected with H. pylori than among uninfected patients.36 Another study in Ethiopia showed that Hb, RBC counts, HCT, MCV, MCH, MCHC, and RDW differed significantly between patients infected with H. pylori and uninfected patients. Moreover, studies conducted in China and Saudi Arabia’s Asir Region also found that RBC, MCV, MCH, and MCHC differed significantly between patients infected with H. pylori and uninfected patients.33,37,38 These differences can be explained by blood loss from peptic ulcers and hemorrhagic gastritis, inhibited iron absorption due to chronic gastritis, vitamin B12 deficiency, and iron deficiency secondary to chronic and atrophic gastritis.33 Differences between our study and previous studies may reflect different methods, sample sizes, target populations, and research areas.
In our study, the prevalence of anemia was slightly but non-significantly higher in the H. pylori–negative group than in the H. pylori–positive group (p = 0.703), while the prevalence of thrombocytopenia was equal between groups (p > 0.999, Table 4). Our findings regarding anemia contradict previous studies showing a significantly higher prevalence of anemia among patients infected with H. pylori than among uninfected patients. A retrospective study in China showed that the prevalence of anemia was considerably higher in the H. pylori–negative group than in the H. pylori–positive group.37 Another study conducted in Makkah, Saudi Arabia, found a positive association between H. pylori infection and idiopathic IDA.39
Regarding thrombocytopenia, a study in Egypt involving 160 patients infected with the hepatitis C virus found that 123 were also infected with H. pylori, of which 67 had thrombocytopenia.40 Thus, in this cohort, the prevalence of thrombocytopenia was significantly higher among patients infected with H. pylori than among uninfected patients (p = 0.039). Notably, 63% of the patients infected with H. pylori who had thrombocytopenia showed good responses and improved platelet levels after eradication therapy. In addition, Rahman et al. found significantly lower platelet counts among 50 patients infected with H. pylori than among 50 controls.41 Moreover, Lei et al. demonstrated that H. pylori activates megakaryocyte apoptosis via the nuclear factor kappa B (NF-κB)/interleukin 17 (IL17) signaling pathway, decreasing platelet production.42 Conversely, Jiao et al. found substantially higher platelet counts among individuals infected with H. pylori than among uninfected individuals,43 which they explained was due to H. pylori binding to von Willebrand factor (VWF) via interactions with glycoprotein Ib (GPIb) receptors on the surface of platelets, with the support of immunoglobulin G, leading to platelet aggregation.44 Moreover, H. pylori was found to stimulate platelets by enhancing selectin P (SELP/CD62P) expression on their surfaces.45
However, Samson et al. found no significant difference in platelet count between 108 patients infected with H. pylori and 600 controls (252 vs. 257 × 109/L),46 consistent with our study. Nonetheless, differences in platelet counts across studies are conflicting, regardless of the mechanism, likely reflecting different patient populations and disease states.
Comparisons of CBC parameters by sex ( Table 5) revealed significant differences between males and females, with Hb, HCT-PCV, and RBC counts higher in males. These findings are consistent with a previous study in Cameroon47 that showed significantly higher CBC parameters in males than in females, as well as another study in Saudi Arabia.39 These differences are likely explained by normal physiology, as females tend to have lower CBC parameters, which is suggested to be due to the menstrual cycle.
Our study had several limitations that should be acknowledged. Firstly, it employed a cross-sectional design, although a prospective cohort design would be optimal for studying CBC parameters. Secondly, since it only examined data from a single polyclinic, the findings may not generalize to Saudi Arabia as a whole. Thirdly, only 152 of the planned 385 patients were included due to the complexity of extracting data from the electronic medical records system used in the polyclinic at King Faisal University, thereby limiting statistical power. Therefore, further studies with larger sample sizes are required to confirm and expand our findings. Fourthly, this study was retrospective, examining data recorded in electronic medical records, which may limit the accuracy of some information, such as determining whether anemia was diagnosed before or after H. pylori infection. Fifthly, some patients were recorded as anemic without specifying the type of anemia or medication history. Moreover, patients had diverse comorbidities (anemia, chronic kidney disease, and inflammatory conditions) that could influence hematological parameters. Finally, In the polyclinic at King Faisal University, CBC reference ranges was defined without specific cutoffs by sex or age.
However, due to the heterogeneity and incomplete nature of the data, multivariate adjustment for all comorbidities was not feasible.
Given the limitations of this study, future research should prioritize prospective cohort studies of CBC parameters conducted in a broader range of populations.
This study revealed no significant differences in CBC parameters between patients infected with H. pylori and uninfected patients. Its findings revealed no associations between H. pylori infection and CBC parameters, as well as anemia or thrombocytopenia. The findings also highlight the need for further studies conducted across a broader range of clinics, as our study cohort was much smaller than the required sample size, limiting the generalizability of our findings to the general population of Saudi Arabia. Moreover, future studies should employ different methods, adjusting for and excluding comorbidities and other confounders.
This article was revised and approved by the deanship of scientific research of King Faisal University in Al-Ahsa, Saudi Arabia (Project No. KFU-REC-2023-DEC-ETHICS1782, Date: 27/12/2023).
Individual informed consent was waived by the Institutional Review Board (Deanship of Scientific Research, King Faisal University) because this was a retrospective study using de-identified data extracted from electronic medical records, with no direct patient interaction. Access to the data was approved by the administration of the polyclinic of King Faisal University in collaboration with the ethics committee.
No supplemental data are available.
The datasets generated and/or analyzed during the current study are not publicly available due to patient confidentiality. However, the data has been made available to the journal’s reviewers and editorial board for the purpose of peer review. For researchers outside of the editorial process, de-identified data may be obtained upon reasonable request to the corresponding author via email ( [email protected]).
The authors would like to thank the clinical pathologist “Dr. Hany Aly Hassan Mohammad” who works in the hematology unit, polyclinic laboratory, King Faisal University for his help in facilitating the data collection process.