Abstract
Objective
This study aimed to assess the prevalence of anemia in Hungary between 2019 and 2022 as detailed data in this regard was not available.
Methods
This retrospective, observational, cross-sectional study enrolled 85628 patients with a median age of 63 (44-76 interquartile range) years admitted to the Emergency Department of the University of Pécs, Hungary, between January, 2019, and December, 2022.
Results
The overall prevalence of anemia was 22.68%. The prevalence of anemia did not change significantly during the study period (2019: 22.30%; 2020: 22.88%; 2021: 22.55%; 2022: 23.00%). However, the prevalence of severe anemia (Hgb<8g/dL) was higher compared to 2019, in each year (2019:2.00%; 2020:2.52%; 2021:2.60%; 2022:2.47%, p<0.001). The increase was observed in each analyzed year among the elderly male patients and in 2021 and 2022 among the elderly female patients. The rising number of patients with COVID-19 diagnosis presenting severe anemia may have contributed to this change. Among all anemic patients, the overall prevalence of microcytic and macrocytic anemia accounted for one-third, while hypochromic and hyperchromic anemia for half of the cases. Hypochromic anemia prevalence decreased and normochromic anemia prevalence increased significantly in each year. The prevalence of microcytic anemia decreased in the year 2020 compared to 2019, the changes being observed among the female patients only.
Conclusions
Over the study period, anemia affected approximately one-quarter of the patients each year, while the proportion of severe anemia increased, especially in the elderly.
Keywords
Introduction
Anemia represents a significant global health challenge due to the high prevalence among reproductive-aged females, and the impact on the quality of life and outcome of co-occurring diseases. Elderly anemic patients have reduced physical performance, and muscle strength associated with a higher risk of falling, more frequent hospitalizations, and an increased risk of mortality. 1 Anemia is associated with a worsened clinical outcome in patients with heart failure,2,3 while several studies concluded that parenteral iron replenishment improves hemoglobin concentration, which will result in improved physical capacity and subsequently lead to reduced hospitalization numbers and mortality.4,5 Anemia is a condition with a large spectrum of etiologies. The most frequent etiology of anemia is the anemia of deficiencies, especially iron deficiency. In older age, multifactorial anemia and anemia of chronic diseases have a higher prevalence.6–9 The World Health Organization (WHO) estimated a global anemia prevalence of 29.9%, with a European prevalence of 18.8% and a 21.7% in Hungary among non-pregnant women of reproductive age in 2019. 10 The Global Burden of Disease Study (GBD) reported an estimated 24.3% prevalence of anemia globally, 14.8% in Central Europe, and 12.7% in the general population in Hungary for 2021. 6 Anemia is even more prevalent among hospitalized patients and has a negative impact on hospitalization duration, readmission rates, and in-hospital or post-discharge mortality.6–8,11 Beverina et al. in a study performed in 2019 at the emergency department of a tertiary care hospital on anemia prevalence, included 22329 patients and reported an overall prevalence of 27.5%, 12 which is higher than the estimation for the general population (5,8% in Italy in 2021). 6 The patients of emergency departments represent a large and heterogenous group regarding their age and medical condition as well. Excluding the most severe cases, which require acute hospitalization, the analysis gains insight into the prevalence of anemia in the general and outpatient clinic population.
The primary aim of this study was the descriptive analysis of anemia prevalence overall and anemia classifications by severity and morphologic types in the outpatient setting at the Emergency Department of the University of Pécs, Clinical Centre, Hungary. The secondary aim of the study was the investigation of the relationship between the available influencing factors and the prevalence of anemia overall and by specific anemia classifications. Tertiary, the effect of the SARS-CoV-2 pandemic on the fluctuations of anemia prevalence overall and anemia classification by severity and morphologic types was also analyzed.
Materials and methods
Study design and setting
This retrospective, observational, cross-sectional study utilized data collected from the tertiary care Emergency Department (ED) of the Clinical Center of University of Pécs, Hungary, serving the southwest region of Hungary and providing healthcare for more than 1 million people, including six Transdanubian counties. The yearly case numbers in the ED for any cause were 41830 in 2019, 41106 in 2020, 43267 in 2021, and 43592 in 2022. The Department is open 0-24, the triage examination takes place right after admission, as in all Hungarian emergency departments, patients are admitted not only with serious conditions. Almost all specialties are represented, except obstetrics; even severely injured pediatric cases are treated in our ED. The collected data spans from January, 2019 to December, 2022.
Data availability and ethical considerations
The reporting of this study conforms to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for cross-sectional studies. 13 The study protocol was reviewed and approved by the Regional Ethical Committee of the University of Pécs (Approval No. 9391–PTE2023, approval date: July 31st, 2023). All procedures involving human data were conducted in accordance with the ethical principles of the Declaration of Helsinki (1975), as revised in 2024.
This study was based exclusively on anonymized, aggregated data. No case-level, directly identifiable, or indirectly identifiable patient information was accessed, used, or reported at any stage of the analysis. As a result, individual patient identification is not possible, and informed consent was not required in accordance with applicable ethical and regulatory standards.
The datasets analyzed during the current study are not publicly available due to institutional data protection regulations, but may be made available from the corresponding author upon reasonable request and with appropriate ethical approvals.
Patient population and data collection
The medical records of adult patients (aged 18 years or older) presenting to the ED during the study period were analyzed. Inclusion criteria required patients to be classified as outpatients (not requiring immediate inpatient admission linked to the ED presentation) and to have had a complete blood count (CBC) ordered and recorded during their ED visit. Patients were excluded if inpatient care was subsequently required, if CBC results were incomplete or unavailable, or if the discharge diagnosis was missing. To increase the relevance of the study findings for national health policy, non-Hungarian citizens were also excluded.
From the initial pool of 123,225 adult cases meeting the selection criteria, 2,160 were excluded due to non-Hungarian citizenship, leaving 121,065 cases. To handle the bias from multiple presentations within a single year for the same condition, the sample with the lowest hemoglobin concentration for patients identified with anemia during that year was used; otherwise, data from the patient’s first presentation in that year were used. After excluding 344 cases due to missing data, this process resulted in a final study population of 85,628 unique patient data for analysis (Figure 1). Flow diagram of data curation.
The collected parameters included patient birthdate, sex assigned at birth, discharge diagnoses (coded according to ICD-10) 14 and complete blood count results. COVID-19 diagnoses were based on rapid antigen tests performed during the ED admission. All laboratory analyses were performed at the Department of Laboratory Medicine, University of Pécs, using a Sysmex XN9000 analyzer.
Definitions
Anemia was defined according to WHO criteria as hemoglobin <120 g/L in women and <130 g/L in men. The classification of anemia by severity resulted in mild (hemoglobin >110 g/L up to the lower limit of normal), moderate (hemoglobin between 80 – 110 g/L), or severe (hemoglobin < 80 g/L) anemia. Morphological classification used the local laboratory reference intervals for Mean Corpuscular Volume (MCV: 80-95 fL; defining Microcytic, Normocytic, Macrocytic) and Mean Corpuscular Hemoglobin (MCH: 28-33 pg; defining Hypochromic, Normochromic, Hyperchromic). Patients were stratified by age (Reproductive:18-49 years, Middle: 50-64 years, Elder: ≥ 65 years) and sex (Female/Male).
Statistical analysis
The statistical approach was selected based on the structure, temporal span, and heterogeneity of the dataset. Owing to the extended study period and the observational nature of the data, analyses focused on descriptive characterization and multivariable modeling rather than classical hypothesis-testing procedures with strict distributional assumptions.
The prevalence of anemia
Yearly and monthly prevalence estimates were calculated for overall anemia, anemia severity categories, and the distribution of anemia morphologies based on mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Monthly proportions of anemic patients within these categories were calculated to evaluate temporal patterns. These descriptive analyses were performed at the case level and served as the basis for subsequent regression modeling.
The analysis of the influencing factors of anemia
Multivariable logistic regression models were applied to examine factors associated with anemia and its subtypes, enabling accounting for potential confounding. Regression modeling was preferred over classical inferential tests, as the latter would not adequately account for confounding introduced by temporal variation, demographic heterogeneity, and diagnostic case mix across the prolonged study period.
Four separate regression models were constructed using the defined outcomes: Anemia (No [reference]/Yes); anemia severity (No anemia [reference]/Mild/Moderate/Severe), anemia morphology by MCV (Normocytic [reference]/Microcytic/Macrocytic) and anemia morphology by MCH (Normochromic [reference]/Hypochromic/Hyperchromic).
Candidate predictor variables were considered based on clinical relevance and data availability. Variables intrinsically linked to the definition or classification of anemia (hemoglobin, hematocrit, MCV, MCH, MCHC) were excluded to avoid circular reasoning. Certain patient-level risk factors (dietary habits, detailed socioeconomic indicators) could not be assessed due to limitations inherent to retrospective data collection.
A backward variable selection approach was initially explored, including age category, leukocyte parameters (total white blood cell count and differential), platelet count, RDW, and platelet distribution width. Following this process and clinical consideration of model interpretability, the final multivariable models retained age category, sex, calendar time, and diagnosis category as predictors. Calendar time was treated as a categorical variable using calendar years (2019–2022), allowing adjustment for secular trends without assuming linearity.
Multicollinearity among predictors retained in the final models was assessed using the generalized variance inflation factor (GVIF). No evidence of problematic multicollinearity was identified (GVIF^(1/(2×df)) values ranging from 1.07 to 1.33). Model results are presented as odds ratios with corresponding 95% confidence intervals and p-values.
The size of the sample was sufficient for stable estimation of the regression parameters.
The effect of the pandemic on the prevalence of anemia
To assess the potential impact of the COVID-19 pandemic on anemia prevalence trends, comparative analyses were conducted between two groups: 1) all anemic patients and 2) anemic patients excluding those with a concurrent COVID-19 diagnosis. Segmented logistic regression models were employed to evaluate changes in prevalence trajectories over defined epidemiological periods, rather than calendar-year categorization. Segment 1 was defined as the time interval between January 2019 and March 2020, representing the pre-pandemic era. Segment 2, ranging between April 2020 and December 2020 represented a shorter period, while Segment 3 and Segment 4 were identical to the previously defined calendar-year categories.
For each segment (excluding the baseline period), separate logistic segmented regression models were fitted using monthly prevalence proportions as outcomes, weighted by the total number of relevant patients per month. The models included time (month), group (with vs. without COVID-19 diagnosis), and an interaction term between time and group. This interaction term tested whether the rate of change in prevalence over time differed between groups within each segment. A p-value < 0.05 for the interaction term was interpreted as evidence of a statistically significant difference in trend trajectories between the two groups during that specific period.
Software
Data management and statistical analyses were conducted using R software (version 4.4.0). The multivariable logistic regression analyses utilized the ‘nnet’ package (for multinomial models) and the ‘car’ package (for GVIF calculation). The segmented regression analysis and data visualization utilized packages including ‘dplyr’, ‘tidyr’, ‘lubridate’, ‘ggplot2’, ‘broom’, and ‘stats’. Trends from the segmented analysis were visualized using line plots displaying monthly proportions for both groups, with superimposed regression lines for each segment. P-values from the trend comparisons (reflecting the significance of the time-by-group interaction within each segment) were noted on the plots where applicable. The threshold for statistical significance was set at p < 0.05 throughout the analyses.
Results
The prevalence of anemia
Overall and yearly distribution of the patients and anemic patients by sex assigned at birth and age categories.
Anemia prevalence differed in the combined analysis regarding the age groups and groups by sex assigned at birth. Among the patients aged between 18 and 49 years, the overall prevalence of anemia was 5.02 % in the male patients, while in the female patients, the prevalence of anemic patients was 13.02%. In contrast, among the middle-aged and elderly patients, the male anemic patients were dominant with 20.26% of males vs 14.37% of females in the middle-aged and 38.10% of males vs 31.38% of females in the elderly group (Table 1).
Overall and yearly prevalence of anemia severity within the different patient groups.
Yearly distribution of the anemic patients by morphologic subtypes of anemia overall, by sex assigned at birth, and by the age categories in the case of the female anemic patients.
In 2019, normochromic anemia accounted for more than half of the anemic patients, followed by hypochromic anemia (one-third) and hyperchromic anemia. In comparison to 2019, in each following year, hypochromic anemia prevalence was lower, while the occurrence of normochromic anemia was increased. In 2021, the hyperchromic anemia prevalence increased, with corresponding changes in the morphologic subtypes only in the female patient group. The observed changes in hyperchromic, hypochromic, and normochromic subtypes both in the overall and in the female patient groups corresponded with the findings in the female patient group aged 65 and older. Thus, over the years, the prevalence of hypochromic anemia decreased, while normochromic anemia increased, especially in the elderly female group (Table 3).
The analysis of the influencing factors of anemia
A binomial logistic regression analysis examined associations between anemia (outcome variable) and age category, sex, year of admission, and diagnosis categories. Male sex was significantly associated with higher odds of anemia (OR: 1.09, 95%CI: 1.05-1.13) similarly to ‘Middle’ (OR: 2.10, 95%CI: 1.99 – 2.23) and ‘Elder’(OR: 5.16, 95%CI: 4.92 – 5.41) age categories compared to the ‘Reproductive’ group. The prevalence of anemia did not change significantly during the years, the analysis showing no significant relationship between Time (Years) and anemia. Compared to the patients with no recorded diagnosis (“Special”), and presenting an anemia prevalence of 11.7%, all diagnosis categories showed significant association with anemia, excepting psychiatric, oto-rhino-laryngology, and connective-tissue diseases (Figure 2). Forest plot of the odds ratios with 95% Confidence Intervals of associations between selected predictors and anemic status as well as anemia severity. Statistical significance of the odds is marked as follows: *(p<0.05); **(p<0.01); ***(p<0.001).
We evaluated associations between the predictors and the severity of anemia (Mild, Moderate, Severe vs. Normal). Age was strongly associated with mild, moderate, and severe anemia, the OR being most increased in the case of severe anemia, in both the ‘Middle’ and ‘Elder’ groups as well. The year of admission was not associated with mild or moderate anemia. A significant association of severe anemia with the year of admission was observed in 2020 (OR: 1.20, 95%CI: 1.05 – 1.39), 2021 (OR: 1.24, 95%CI: 1.08 – 1.42), and 2022 (OR: 1.15, 95%CI: 1.00-1.32), respectively. Immuno-haematologic conditions, malignancies, endocrine-metabolic, dermatologic, COVID-19, and infectious diseases were strongly associated with mild, moderate, and severe anemia. Trauma-related diagnoses, neurologic and pulmonary diagnoses were associated with mild and moderate anemia (Figure 2).
The analysis of associations between the predictors and the morphologic type of anemia revealed that male sex was significantly associated with hyperchromic (OR 1.75, 95%CI: 1.59-1.93) and macrocytic anemia (OR: 1.48, 95%CI: 1.36 – 1.61), and was negatively associated with hypochromic (OR: 0.59, 95%CI: 0.55 – 0.633) and microcytic (OR: 0.63, 95%CI: 0.58 – 0.68) anemia. The ‘Middle’ age category was associated with hyperchromic, macrocytic, and negatively associated with hypochromic and microcytic anemia. The ‘Elder’ age category was negatively associated with hypochromic and hyperchromic, microcytic anemia, and a positive association was observed with macrocytic anemia. The year of admission was negatively associated with microcytic anemia in 2020 (OR: 0.85, 95%CI: 0.77 – 0.96) and marginally positively associated with macrocytic anemia (OR: 1.13, 95%CI: 1.00 – 1.26). Subsequently, 2021 was negatively associated with hypochromic anemia (OR: 0.86, 95%CI: 0.79 – 0.95) (Figure 3). Forest plot of the odds ratios with 95% Confidence Intervals of associations between selected predictors and the morphology of anemia. Statistical significance of the odds is marked as follows: *(p<0.05); **(p<0.01); ***(p<0.001).
In Supplementary Table 1, the pharmaceutical product sales data showed a marked increase in each year compared to 2019, with the maximum increase in 2021 (79.42%) regarding iron-containing pharmaceuticals.
The effect of the pandemic on the prevalence of anemia
The impact of the COVID-19 diagnosis on the findings was further examined. To assess the impact of cases diagnosed with COVID-19, we performed a segmented regression analysis of monthly anemia prevalence trends. The analysis of monthly anemia prevalence was conducted with the inclusion of COVID-19 patients (red color on plot) and also with the exclusion of these patients (blue color on plot). The presence of COVID-19 cases was associated with a slight and significant increase in monthly anemia prevalence in the year 2021 (p = 0.0122) (Supplementary Figure 1).
Performing the same analysis by anemia severity classification revealed that COVID-19 cases exerted a stronger influence on the prevalence in the severely anemic group, although the difference was not statistically significant, while moderate and mild anemia were less influenced by COVID-19 infection. COVID-19 cases did not influence the morphologic subtypes of anemia (Supplementary Figure 1). The logistic regression models also revealed a strong association of COVID-19 with anemia (OR: 2.05, 95%CI: 1.62 - 2.64). The presence of a COVID-19 diagnosis was associated with the severity of anemia, in the following order: mild anemia (OR: 1.68, 95%CI: 1.24 – 2.28), moderate anemia (OR: 2.31, 95%CI: 1.56 – 3.44), and severe anemia (OR: 3.83, 95%CI: 1.69 – 8.63) (Figure 2). COVID-19 was associated with macrocytic anemia (OR: 2.91, 95%CI: 1.16 – 7.30) (Figure 3).
To assess a possible background for these observed changes, we further analyzed the severely anemic patients. Severely anemic patients have shown high rates of COVID-19 diagnoses, accounting for more than a fourth of the cases in 2020 (27.42 % [23.67-31.51] CI95%), 2021 (29.06% [25.43-32.98] CI95%), and 2022 (29.2 % [25.62-33.05] CI95%). Overall, the prevalence of COVID-19 was lower in every analyzed year than in the severely anemic group with 12.76 % [12.31-13.24] in 2020, 15.3% [14.82-15.79] in 2021, and 22.13% [21.6-22.67] in 2022, respectively. The distribution of diagnoses in severe anemic patients was similar in most of the diagnosis categories during the study period. The yearly occurrence of gastroenterology and immunohematology diagnoses among severely anemic patients decreased each year, compared to 2019 (Supplementary Table 2).
Discussion
The Emergency Care Unit of the University of Pécs manages a high number of patients annually. The analysis of the acquired data revealed that the yearly distribution of patients stratified by sex assigned at birth and age categories was similar during the analyzed time interval. The overall yearly prevalence of anemia presented slight fluctuations, which were statistically not significant. In this study, the data have shown a lower yearly prevalence of anemia in women of reproductive age (14.66%) in comparison with the 21.7% WHO prevalence estimation for Hungary in 2019. 10 According to the findings of this study, in comparison with the WHO estimates, the prevalence of anemia was lower in each year. WHO estimates reveal an increasing trend in the prevalence of anemia (21.70% in 2019 vs 23.30% in 2022), which could also be observed in this study. 10 In the age group between 18-49 years, anemia was more frequent in females than in male patients, while in the older age groups, anemia prevalence was higher in males compared to females.
The estimation of the overall anemia prevalence according to the GBD study in Hungary, for 2021, was 12.7%. Our study group presented a higher prevalence (22.68%), similar to the results of Beverina et al. (27.5%), who examined patients in the emergency department, and the mean age of the enrolled patients (56 +/- 25 SD) was closer to our study (60.34 +/- 20.05 SD).2,6
The differences observed in the prevalence of anemia may be explained by differences in the case-mix of the two Emergency Departments. Our study only included outpatients treated at the ED of the University of Pécs, in comparison with the Beverina et al.’s study, the goal of which was to assess anemia prevalence in unselected patients referring to the ED of Lignano, Italy. 12 The overall prevalence of anemia showed a slightly increasing tendency during the years when COVID-19 cases accounted for a high percentage of patients requiring emergency care. During these years, globally, the healthcare systems emphasized the focus on the therapy and diagnosis of acute COVID-19 patients, while anemia prevention and treatment were possibly hindered due to the pandemic situation. The number of severely anemic patients increased significantly during the analyzed time interval.
The analysis of the distribution of diagnoses in the severely anemic patient group showed a high frequency of COVID-19 patients starting in 2020, which could partially explain the continuously increasing number of severely anemic patients compared to 2019. Conversely, the number of patients with gastroenterological and immunohematological conditions decreased significantly each year, possibly due to the temporarily altered patient routes imposed by the national regulations based on international recommendations and guidelines to reallocate resources and to address acute changes in the management of patients. The higher integration, accessibility, and faster adaptation of telemedicinal patient care may have also played a role in the reduction of cases in these diagnosis groups. 15 The number of severely anemic patients with underlying gastrointestinal and immunohematology conditions reduced, but was strongly associated with this condition. The rising number of severely anemic patients with a COVID-19 diagnosis contributed to a significant overall increase in the frequency of this patient group. Between 2020 and 2022, the higher number of patients diagnosed with COVID-19 resulted in an increased overall prevalence of anemia, which was most expressed in the severely anemic group, but also present in the mild and moderately anemic patients. These findings suggest that anemia, especially severe anemia, may have occurred more frequently in the patients diagnosed with COVID-19, a phenomenon also emphasized by several authors.16–18
Altogether, these findings suggest that the most clinically relevant temporal change in this cohort was the increase in severe anemia prevalence, particularly among the elderly. Microcytic and hypochromic anemia is most frequently associated with iron deficiency, however, the lack of microcytosis does not exclude the possibility of iron deficiency. Statistically significant differences were observed in hypochromic and normochromic, microcytic and macrocytic categories, but these changes were generally modest in absolute terms. Therefore, the morphologic findings in this study are interpreted as secondary descriptive features of the cohort. The available data were insufficient to clarify their underlying mechanisms in greater detail. Our results draw attention to the need for further examinations to identify and correct deficiencies that frequently cause anemia.
According to the results of this study, normocytic anemia accounts for a high proportion of anemia, frequently related to underlying chronic inflammation, bleeding, and renal diseases. Among the etiologies of anemia of deficiencies, the most frequent ones are iron, vitamin B12, and folate deficiencies. The lack of iron leads not only to anemia but also increases susceptibility to infections by suppressing the immunological response to pathogens, 19 and alters several neural functions (restless leg syndrome, brain fog). 20 Furthermore, iron is a component of several enzymes, influencing the cytochrome oxidase system and electron transport capacity. Thus, iron deficiency can affect a broad range of physiological processes and is not exclusively related to the development of anemia.
The National Health and Nutrition Examination Survey (NHANES) 2007-2018 analysis reported vitamin B12 deficiency (<200 pg/mL) in 3.6% and insufficiency (<300 pg/mL) in 12.5% of US adults, with variable global prevalence. 21 Classic clinical manifestations are now less frequent due to earlier testing and supplementation. 22 Metformin, the first-line oral antidiabetic agent, causes dose- and duration-dependent B12 malabsorption, highlighting the need to monitor deficiency in the growing diabetic population.23–25
Folate deficiency is usually coexistent with other nutrient deficiencies, based on poor diet, malabsorptive disorders, and/or chronic alcohol consumption.26,27 Larger amounts of folate intake can treat macrocytic anemia, but not the neurological damage related to vitamin B12 deficiency. 28 The prevalence of alcohol-related disorders has increased in Hungary, affecting approximately 20% of the adult population, and worsened during the COVID-19 pandemic. 29 This may partially be an explanatory phenomenon for the observations regarding the increased prevalence of macrocytic anemia. Morphologic classification based on MCV and MCH may orient the diagnostic approach, but confirmation requires complementary laboratory assessment such as iron studies, vitamin B12 and folate levels, renal function parameters, inflammatory markers, and, where appropriate, further hematologic and gastrointestinal evaluation. In a study performed recently to assess the medical approach to an anemic state at an internal medicine unit in Italy, Randi et al. emphasized the low acknowledgment of anemic status at the time of discharge. Reportedly, anemia management was only adequate, specifically in patients admitted due to severe anemia. 30 Awareness of anemia in high-risk population groups, in the elderly, vegetarians, and/or patients with comorbidities at the clinical and educational level, could be beneficial. Anemia is associated with worsened clinical outcomes, and the lack of therapy and prevention maintains its higher prevalence. Prevention and/or adequate diagnosis and therapy of the underlying causes of anemia would contribute to a lower anemia prevalence and may improve hospitalized patients’ clinical outcomes.31,32
Current clinical guidelines emphasize that in adult populations, iron deficiency anemia serves as a sentinel sign for occult blood loss; thus, a rigorous gastrointestinal evaluation in these cases is needed. 33 As noted in standard workflows, the detection of microcytic anemia in men and postmenopausal women serves as a definitive indication for bidirectional endoscopy to exclude malignancies, given the 6–15% prevalence of colorectal cancer in this demographic group.33,34
Conversely, the prevalence of normocytic anemia among patients with renal failure, infectious diseases, or circulatory system disorders highlights the complex etiology of anemia of chronic disease (inflammation) and hypoproliferative states.35,36 In these clinical contexts, anemia is typically driven by cytokine-mediated iron sequestration or blunted erythropoiesis rather than nutritional deficits. 35 This aligns with the diagnostic framework, suggesting that normocytic presentations prioritize the assessment of renal function, inflammatory markers (CRP), and marrow response (reticulocytes) over immediate endoscopic investigation. 37 The association in our cohort between normocytic indices and cardiovascular diseases, endocrine and metabolic, and renal-urogenital diseases is in line with the view that these cases represent multifactorial pathology requiring a broader expanded laboratory panel rather than isolated iron replacement. 37
The stratification of our results by anemia severity and morphology supports a structural diagnostic approach, but the associations should be interpreted cautiously. In this retrospective dataset, containing information on ED visits, discharge diagnoses primarily reflect the clinical context of the acute encounter. Therefore, the diagnosis-category analyses are best understood as describing encounter-level case mix associated with anemia detection in the emergency setting, and not in the context of cause-and-effect relationship between these conditions and anemia. This aligns with the targeted strategy where patients with microcytic anemia are rapidly triaged toward iron studies and gastrointestinal evaluation, while those with normocytic anemia warrant screening for renal dysfunction and inflammatory etiologies.37,38 Integrating this morphological awareness into the admission workflow could optimize resource utilization, ensuring that invasive procedures like endoscopy or bone marrow examination are reserved for the highest-yield populations. 39
In our previous retrospective investigation, analyzing data between January 2020 and December 2022, we examined the relationship between COVID-19 and anemia. Our findings hinted a significant association between the two conditions, observing a bidirectional relationship, with higher proportion of COVID-19 diagnoses among anemic patients and a higher proportion of anemia among COVID-19 patients annually. 40 This pattern highlights the possible role of acute infection and inflammatory processes in the development of anemia, while also suggesting that anemia may increase susceptibility to infection. The present study expands on these findings by evaluating the prevalence of anemia by morphologic subtype and severity, while also controlling for confounding variables to reduce bias.
The limitations of this paper include the retrospective nature of the study, reducing the availability of variables that were not routinely recorded during the study period. Focusing exclusively on patients from a single center is a second limiting factor for the applicability and external validity of the findings in other populations or settings. During the investigation of the causes of signs and symptoms requiring emergency care in patients admitted to the emergency department, only diagnoses related to these issues are documented. As a result, the collection of these diagnoses does not provide comprehensive insight into other medical conditions affecting the patient. The exclusion of non-Hungarian citizens does not eliminate heterogeneity in background, migration status or socioeconomic position among Hungarian citizens, which remain unmeasured potential confounders. Pregnant female patients may be admitted to the ED without being aware of their pregnancy, such occurrences could not be identified or excluded, and therefore remained in the analyzed study group.
Furthermore, while the pharmaceutical data provides a robust overview of market trends for iron and vitamin supplements, it is limited to the volume of units sold. Pharmaceutical sales data do not provide case-level information about individual supplements and vitamin consumption but highlight local trends in the region. These results suggest the hypothesis about an improved substrate availability in parallel with slightly decreased microcytic anemia prevalence. The lack of data regarding precise dosages, concentrations, or individual patient adherence means these results should be interpreted as indicators of general availability rather than exact physiological supplementation levels. The patients analyzed in this study were older compared to the general population of Hungary, limiting the generalizability of our results. The ratio of males and females was similar to that of the general population. 41 The epidemiological characteristics of patients involved in this analysis assumably resembles that of Hungarian outpatient clinics, as we included only outpatients of ED in this study. The generalizability of this study is mainly limited to similar ED or acute-care outpatient populations in Hungary and possibly Central Europe. The external validity of this study’s findings is only applicable to similar settings, such as other EDs in Hungary or Central Europe, where patient demographics, healthcare structures, and nutritional and lifestyle patterns align with the study context. The study also provides a valuable reference point for regions with comparable healthcare challenges during and after the COVID-19 pandemic. This study may be used to inform local healthcare providers and may also support the optimal resource allocation strategy.
Most of the anemic conditions can be treated, improved, or prevented. This study serves as a basis for future studies, especially in Hungary and Central Europe. In Hungary, the number of patients with anemic conditions is high, although it remains less frequent compared to the global prevalence of anemia according to the WHO estimates in reproductive-aged women. This study provides a reference point for future work on anemia in comparable settings.
Conclusion
This descriptive observational study revealed that anemia affected 22-23% of adult emergency outpatients in Pécs, Hungary. The prevalence of severe anemia increased during the four-year period, especially in the elderly.
Supplemental material
Supplemental material - Unchanged prevalence and increased severity of anemia from 2019 to 2022 in emergency care outpatients: A cross-sectional study from a tertiary care university hospital of Pécs, Hungary
Supplemental material for Unchanged prevalence and increased severity of anemia from 2019 to 2022 in emergency care outpatients: A cross-sectional study from a tertiary care university hospital of Pécs, Hungary by Zsuzsanna Faust, Margit Solymár, Enikő Nemes-Nagy, Sándor Pál, Hussain Alizadeh, Péter Kanizsai, Boglárka Finta, Veronika Dolmán, Nelli Farkas, Barbara Réger, and Attila Miseta in Science Progress.
Supplemental material
Supplemental material - Unchanged prevalence and increased severity of anemia from 2019 to 2022 in emergency care outpatients: A cross-sectional study from a tertiary care university hospital of Pécs, Hungary
Supplemental material for Unchanged prevalence and increased severity of anemia from 2019 to 2022 in emergency care outpatients: A cross-sectional study from a tertiary care university hospital of Pécs, Hungary by Zsuzsanna Faust, Margit Solymár, Enikő Nemes-Nagy, Sándor Pál, Hussain Alizadeh, Péter Kanizsai, Boglárka Finta, Veronika Dolmán, Nelli Farkas, Barbara Réger, and Attila Miseta in Science Progress.
Supplemental material
Supplemental material - Unchanged prevalence and increased severity of anemia from 2019 to 2022 in emergency care outpatients: A cross-sectional study from a tertiary care university hospital of Pécs, Hungary
Supplemental material for Unchanged prevalence and increased severity of anemia from 2019 to 2022 in emergency care outpatients: A cross-sectional study from a tertiary care university hospital of Pécs, Hungary by Zsuzsanna Faust, Margit Solymár, Enikő Nemes-Nagy, Sándor Pál, Hussain Alizadeh, Péter Kanizsai, Boglárka Finta, Veronika Dolmán, Nelli Farkas, Barbara Réger, and Attila Miseta in Science Progress.
Footnotes
Ethical considerations
This study was conducted in accordance with the Helsinki Declaration of 1975 as revised in 2024. The study is reported according to STROBE guidelines. This study was approved by the Regional Ethical Committee for the Research Ethics of the University of Pécs (Approval no. 9391 – PTE2023, Date of approval: July 31st, 2023).
Consent to participate
Informed consent was not required for this study, as it was based on anonymized, aggregated data and did not involve the collection or analysis of identifiable individual-level patient information.
Author contributions
Funding
This research was supported by a grant from the University of Pécs Medical School (Szolcsányi János Research Fund No. 2025-04 to Zs.F.).
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
The datasets generated and/or analyzed during the current study are not publicly available due to institutional data protection regulations but are available from the corresponding author upon reasonable request and with appropriate approvals.
Supplemental material
Supplemental material for this article is available online.
References
Supplementary Material
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