Anemia is among the most common hematological disorders worldwide and makes up an important public health problem in both developing and developed countries. It is defined as a reduction in the concentration of hemoglobin or number of red blood cell (RBC) below the critical level necessary to sustain the physiological oxygen demands of an individual. Since hemoglobin encapsulates oxygen transport to tissue, anemia disrupts tissue oxygen delivery, leading to fatigue, muscular weakness dizziness exertional shortness of breath, decline in physical capacity and diminishing physical quality of life. Yet, clinical presentation and consequences are varied as the severity duration etiology, age, and physiological context of the afflicted individual [1,2]. The World Health Organization states that anemia always should be seen as not a disease per-se but rather a sign of a range of underlying nutritional infectious inflammatory chronic genetic and blood-loss associated conditions1 [1].

Anemia has an important clinical significance other than decreased hemoglobin concentration. Mild to moderate anemia may impair physical function and work capacity in particular in persons with predisposing chronic illnesses. Severe and prolonged anemia may compromise cardiovascular function and may worsen the pre-existing systemic illness. As observed in old age, anemia may be tied to physical and mental morbidity and mortality and may be present and other conditions, such as chronic renal failure, inflammatory diseases, nutritional deficiency, neoplasm, and marrow disorder [4]. Anemia also could impair behavioral and psychomotor development in children and could result in decreased activity and productivity of adults [5].

The etiology of anemia is often complex and causative factors often coexist. Iron deficiency may be a consequence of dietary deficiency malabsorption increased physiological requirements or blood loss. Folate and vitamin B12 deficiency could bring macrocytic or megaloblastic anemia, whereas acquired abnormalities of hemoglobin formation like thalassemia and sickling syndromes can give chronic hemolytic or microcytic anemia. Chronic infections, inflammations, neoplasms, and various forms of chronic renal failure may give anemia secondary to impaired erythropoiesis, deranged iron metabolism, decreased erythropoietin or excess RBC destruction [2,3]. Clinically so anemia is assessed by considering the Hb together with red cell indices reticulocytes peripheral blood appearances, iron status, other vitamin values, renal function and any other relevant tests.

Anemia is mainly relevant in the Indian context where malnutrition infection chronic illness, inequity, and restricted access to appropriate healthcare can often be lurking under the same roof. Though a significant focus has been centered on anemia in children adolescents pregnant and other reproductive age group women, adult men and non-pregnant women of reproductive age are also important target groups. As shown by frequency data from the national survey, anemia remains a common disease even in Indian adults, including women, and may not necessarily be restricted to maternal and childhood contexts [6]. Anemia persists despite nutrition supplementation and public health efforts, indicating the determinants for anemia are also multi-factorial and arguably should not be ascribed solely to iron deficiency.

Kerala is an important location to study anemia, as there is unique nation specific demographic socioeconomic nutritional, and health issues that exist within the state. Despite having a relatively advanced health care structure, and favorable health indicators compared with other states in India, anemia remains prevalent among various segments of the population within Kerala. The National Family Health Survey has identified the presence of anemia among both women and men in the state of Kerala, indicating that the issue of anemia bears not only on developing states of India, but on more advanced states as well [7]. Disparities in dietary habits, socioeconomic status, chronic disease prevalence, alcohol consumption rates, nutritional behaviors, and diagnostic and therapeutic access and ways may all be factors that support these variations in three categories of anemia.

Palakkad district is a relevant study population with its large rural population and wide variation in socioeconomic and occupational groups. Certain other factors may be prevalent in rural communities like suboptimal nutrition, dependence on locally available foods, occupational exposures, underutilization of healthcare services, certain chronic infections, gastrointestinal blood loss, alcohol intake or late presentation with chronic illnesses. Hospital based population may also exhibit different pattern of etiology and severity of anemia against community survey because large numbers of admission to medical wards have both acute and chronic illness also. Knowledge of such variations at individual levels may be useful in diagnostic evaluation and clinical management.

There is a large amount of literature on the subject of anemia in various high-risk groups. Though, far less attention has been paid to the etiological spectrum, severity, and risk factors connected to anemia among general medical hospital admissions in a community-based context, mostly in an unselected population from a rural district of Kerala. The assessment of anemia in a hospital-based setting helps to identify clinically relevant etiologies of anemia seen in everyday settings of medical practice. It can also serve in identifying aspects of potentially preventable risk factors for anemia. This is important considering in reality anemia may represent an unrecognized feature of nutritional depletion, underlying disease, occult blood loss, renal impairment, hemoglobinopathy, or other systemic disease states.

Because of this, the present study was undertaken with what comes next objectives: to determine the etiological spectrum and prevalence of anemia among adult patients admitted to a district hospital of Palakkad Kerala to assess the severity of anemia, and to evaluate some selected sociodemographic, clinical, nutritional, and lifestyle-related risk factors related to anemia. The present effort to document local magnitude and etiology of anemia among adult medical in-patients will be a significant addition to existing body of knowledge on anemia among adult medical in-patients and will generate evidence to promote appropriate diagnostic evaluation, rational management and future public health responses [8].

2.1 Study Design and Setting A hospital based cross sectional laboratory study was undertaken in the Department of General Medicine, District Hospital Palakkad Kerala. The prevalence and etiological spectrum of anemia, its severity and associated risk factors among the adult and adolescent patients admitted in the medicine wards was studied. The study was carried out over a span of one year in the Department of General Medicine from May 2021 to April 2022. 2.2 Study Population The study population included all patients aged above 13 years, who were admitted to the Department of General Medicine, District Hospital, Palakkad during the study period and found to have anaemia. The definition of anemia for this study is a hemoglobin concentration less than 11 g/dl. Patients were identified during their hospital admission using clinical history and investigations from the laboratory investigations routine to the hospital admission. Patients who fit the criteria, were recruited consecutively from the general medical departments over the period of study. 2.3 Sample Size and Sampling Technique The minimum sample size was determined using the standard formula for sample size estimation for cross sectional study (z2pq/d2) where Z is the standard normal deviate at the chosen confidence level, p the estimated prevalence, q = 1 p, and d the desired precision. Assuming a maximum estimated prevalence of 59%, a confidence level of 95%, and an absolute precision of 5%, the minimum sample size derived was about 384 respondents. Consecutive sampling was used and included all clinically diagnosed patients presented in the outpatient clinic fulfilling the inclusion criteria until the sample size was attained. 2.4 Eligibility Criteria Patients>13 years of age with a hemoglobin concentration<11g/dl and admitted to the Department of General Medicine, District Hospital Palakkad during the study period were included. Pregnant women were excluded because pregnancy is tied to physiological changes in hematological values that could complicate interpretation of their hemoglobin and other complete blood count indices. Patients who received a blood transfusion within 2 months of admission were excluded because their recent transfusion could change their hematological values and complicate assessment of their etiology of anemia. Patients who refused to give consent were also excluded. 2.5 Data Collection Information was collated using a predesigned and structured proforma. Participants were first given an information sheet explaining the aims and process of the study and written consent was obtained. Each participant had a detailed history and clinical examination and relevant laboratory and other investigations performed given the clinical condition. Information for demographic data, clinical features, relevant medical history and possible risk factors was obtained. Case records were further analyzed to obtain clinical details and laboratory findings. 2.6 Hematological Investigations All subjects underwent a complete hemogram in the Department of Pathology. Around 3 mL of venous blood was aseptically withdrawn into an ethylenediamine tetraacetic acid (EDTA) vacutainer. This sample was then analyzed by an automated haematology analyzer. The complete hemogram parameters evaluated were Hb concentration, red blood cell (RBC) count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC), total leukocyte count and platelet count. These haematological indices were then used to both establish a pattern of anemia and to evaluate its severity, and to outline the probable etiology of the anemia. 2.7 Evaluation of the Etiology of Anemia All patients found to be anaemic underwent further assessment based on their presenting history and initial hematological investigations. Further investigations were carried out where indicated, to establish the etiology of the anaemia. These included peripheral blood smear, iron studies, serum vitamin B12 assay, liver function test, renal function test ultrasonogram bone marrow aspiration and other relevant specialised investigations as clinically indicated. The final etiology categorization was based on the clinical features, hematological parameters, peripheral blood film features, biochemical investigations, imaging findings and relevant specialised investigations where indicated. 2.8 Assessment of Severity of Anemia Anemia severity was expressed by the hemoglobin levels and a World Health Organization classification system was used to determine categories of severity. The classification was used to define anemia severity levels for individuals with mild, moderate, and severe anemia. This classification was then compared to patient demographics, blood parameters, clinical features and etiological factors. 2.9 Study Outcomes The main outcome of the study was the pattern and causes of anemia among the study population admitted in Department of General Medicine. The prevalence of anemia was the primary outcome of the study. Others study outcomes were severity of anemia and the association of anemia with some demographical clinical nutritional and lifestyle related risk factors. Hematological profile including RBC indices, were also assessed with the purpose of establishing the morphological classification of anemia and to help in differential diagnosis. 2.10 Statistical Analysis The obtained data were entered into Microsoft Excel and analyzed with Statistical Package for the Social Sciences (SPSS version 20.0). For continuous variables, measures of central tendency and dispersion were calculated, while measures of frequency and proportion were used for categorical variables. The independent t test was used to compare parametric data between groups. Chi-square test was used to test for the existence of association among categorical variables. P value less than 0.05 (two-sided) was considered statistically significant. The results were expressed in tables and graphs (bar, pie charts) to show the frequency and etiological patterns of anemia, severity of anemia and the association of anemia with various study variables. 2.11 Ethical Considerations Ethical approval of the study was obtained from the Institutional Human Ethics Committee before participating in the study. The participants received information about the study, had signed an informed consent before participating in the study, and participated only with their consent. Participation was voluntarily and not compelled and was not affected by any treatment or procedure, other than it. The routine procedure of the diagnostic assessment or hospital care was not modified or changed. Approval to access clinical and laboratory data was obtained.

A total of 384 anemic patients admitted to the Department of General Medicine was studied over the study period. Ages ranged from 14 to 96 years, with a mean of 61.8±16.4 years. Patients in the age group 6170 years formed most of the study subject population (30.5%) followed by the age group 7180 years (23.4%). Females were the majority constituting 68.2% of the study subject population. On occupational status, manual labours formed the majority (41.9%) followed by unemployed participants (28.9%).

Table 1. Sociodemographic characteristics of the study population

Fatigue was the major presenting complain in 75.8% of patients, followed by shortness of breath (66.9%), decreased food intake (63.3%), pedal edema (61.2%) and palpitation (55.7%). Pallor was noted in 99.0% of patients and edema in 65.6%. Features of deficiency on nutritional and general physical examination were common- glossitis in 67.7%, alopecia in 57.3% and koilonychia in 51.3%. Various risk factors identified were- vegetarian diet in 23.2%, alcohol consumption in 19.0%, walking barefoot in 9.1% and poor hygiene in 7.3%. The commonest co morbid illness was diabetes mellitus in 50.5% patients followed by hypertension in 22.7% and chronic kidney disease in 11.5%.

Table 2. Clinical characteristics, risk factors, and comorbidities of the study population

Hemoglobins ranged from 2.7 to 10.0 g/dL with a mean of 6.37±1.94 g/dL. Severe anemia (WHO-based classification) was present in 68.8% of participants, with 31.2% having moderate anemia. The mean corpuscular volume (MCV) was 69.7±17.0fL, which was consistent with microcytic red cell morphology. The mean corpuscular hemoglobin (MCH) and the mean corpuscular hemoglobin corpuscular concentration (MCHC) were 25.9±5.2PG and 30.2±3.1g/dL respectively. The morphological pattern of participants on peripheral smear showed predominantly microcytic anemia in 67.4%, normocytic anemia in 16.4% and macrocytic anemia in 14.8%.

Table 3. Hematological profile and morphological pattern of anemia

Iron deficiency anemia made up the largest etiology being present in 63.8%. Vitamin B12 deficiency was found in 12.0%. The remaining approximately 13.3% was due to anemia of chronic disease when these were grouped together; chronic kidney disease, chronic liver disease, malignancy, and autoimmune disease. Anemia due to blood loss totalled 13.3% of the etiologies listed in the diagnostic classification. The other etiologies had lower incidences and included multiple myeloma thalassemia dimorphic anemia, aplastic anemia, drug induced anemia, hemolytic anemia.

Of the patients with iron studies, the mean serum iron concentration was 34.7±19.6, the mean TIBC(Total iron binding capacity) was 494.8±75.0 and the mean transferrin saturation 13.5±5.7. Serum vitamin B12 was performed in 64 patients. The laboratory data, with the peripheral smear assessment and other investigations, assisted the etiological classification.

Table 4. Etiological distribution of anemia

Severity of anemia was a lot connected to a number of demographic, clinical, and risk-factor variables. The mean age in the severe anemia group (63.49 ±15.61 years) was quite a bit higher than that in the moderate anemia group (58.25±17.40 years) (P=0.008). Sex showed no statistically significant association with severity of anemia (P=0.055) and there was no significant difference in mean haemoglobin concentration between females and males (P=0.765).

Vegetarian diet, alcohol consumption, walking barefoot and poor hygiene correlated with severity of anemia, respectively. Severe anemia was present in 73 of 89 vegetarian patients compared with 191 of 295 non-vegetarian patients (P=0.035). In participants reporting alcohol consumption 59 of 73 had severe anemia compared with 205 of 311 reporting no alcohol consumption (P=0.002). Walking barefoot and poor hygiene also correlated with increased severity of anemia.

Table 5. Factors associated with severity of anemia

Like, there was also a statistically significant association between the degree of anemia and what comes next cardiovascular and respiratory examination findings. The presence of severe anemia in these cases was highest were raised jugular venous pressure, S3 gallop, ejection systolic murmur and pulmonary crepitations (P.<0.001 for all). These results show that the patients suffering from severe anemia more commonly showed clinical features indicative of cardiovascular and respiratory deterioration.

Figure 1. Age and sex distribution of the study population.

Figure 2. Distribution of participants according to clinical symptoms at admission.

Figure 3. Morphological pattern of anemia based on peripheral blood smear examination.

Figure 4. Etiological distribution of anemia among study participants.

Figure 5. Distribution of participants according to severity of anemia.

Overall, it was shown that the overwhelming majority of anemia encountered among a cohort of hospitalized patients was severe and morphologically microcytic and that iron deficiency was the primary etiological agent documented. Advanced age, certain selected nutritional and lifestyle factors and clinical signs indicative of heart or lung failure were connected to increased severity of anemia.

In the present study 384 patients with anemia admitted in Department of General Medicine, District hospital, Palakkad were studied. The age of the study population was 14-96 years with a mean of 61.8±16.4 years. Most of the patients in the present study were in the age group 61-70yrs. Similar to previous observations, the greatest prevalence of anemia was found among elderly people in our series [9]. This may be explained from higher incidence of chronic diseases, nutritional deficiencies, renal dysfunction, malignancy, and aging in old people. Females comprised 68.2% of the study population. There was no statistically significant difference between the sex distribution of severity categories (p=0.055). The mean hemoglobin values between the females and males were also statistically comparable (6.392±1.970 g/dL vs. 6.328±1.895 g/dL; p=0.765). The higher numbers of females concur with findings of other studies with a greater burden of anemia among females [10]. Manual workers (41.9%) and unemployed individuals (28.9%) made up most of the occupational groups and this may be illustrative of the effect of socioeconomic factors, nutritional inadequacy and limited health care experiences reported previously [10]. Diabetes mellitus (50.5%), hypertension (22.7%), chronic kidney disease (11.5%) and hypothyroidism (9.9%) were the most common comorbidities. Diabetes was not statistically connected to the severity of anemia (p=0.448). The low number of patients with some of the other comorbidities made it difficult to analyze associations with severity of anemia. Several previous research shows the presence of anemia in large number of patients with chronic kidney disease, hypertension, hypothyroidism, malignancy, and other chronic conditions [11]. These differences may be related to difference in the study population and clinical practice setting. Of these possible risk factors, 23.2 % of patients were vegetarian, 19.0% took alcohol, 9.1% walked barefoot. Bleeding manifestations were reported in 3.9% and recent or old/inactive infection in 3.1%. Significant correlation was found in vegetarianism, alcohol intake, barefoot walking and unhygienic conditions with severity of anemia. These should though be interpreted with caution as the cross-sectional study design does not confer causality to them. Nutritional status and bioavailability of iron in diet are major contributing factors to anemia where there is inadequate dietary intake [15]. Underweight is found in majority (61.5%) with BMI< 18.5 kg/m 2. Severe anemia was detected in 64.4% of underweight women versus 75.7% among women with BMI≥18.5kg/m 2 (p=0.020). The link between nutrition and anemia is a complex one and is influenced by intake inflammation chronic disease and socioeconomic factors. Nainggolan et al reported an increased risk of anemia in underweight women [12]. Fatigue was the presenting feature most frequently encountered (75.8%) followed by breathlessness (66.9%), reduced food intake (63.3%), pedal edema (61.2%) and palpitation (55.7%). Exam-ination features of glossitis, alopecia, and koilonychia was also commonly observed. Raised JVP S3 gallop, ejection systolic murmur and pulmonary crepitations were a lot observed in 69% severe anemia (p.<0.001), which may be a reflection of the impact of severe anemia in the cardiovascular system; But cardiovascular and pulmonary coexisting disease may also have influenced these observations. The average hemoglobin was 6.37±1.94 g/dL, with 68.8% of patients suffering from severe anemia. There were a greater proportion of elderly patients in the severe anemia group, 63.49 ± 15.61 years compared with 58.25 ±17.40 years with moderate anemia (p=0.008). This finding is consistent with earlier reports that the frequency of moderate and severe anemia becomes higher as age increases [14]. Iron deficiency anemia was the most common etiological diagnosis seen in 63.8% of patients and corresponded to the dominance of microcytic hypochromic anemia observed on peripheral smear (66.4%). The iron profile revealed low serum iron and transferrin saturation with increased TIBC. These findings confirm iron deficiency to be an important cause. Six patients showed positive stool occult blood test, which may have contributed to iron deficiency through chronic gastrointestinal blood loss. In a study done previously, inadequate dietary iron intake and less bioavailability of iron have been highlighted as key causes of iron deficiency [15]. The prevalence of B12 deficiency was 12.0% and that of anemia of chronic disease 13.3%. The prevalent chronic disease-causing anemia of chronic disease was chronic kidney disease. Blood loss anemia was seen in uterus fibroids and gynecological malignancies. Less common causes were multiple myeloma, thalassemia aplastic anemia, hemolytic anemia and drug induced anemia. The presence of anemia in patients with chronic disease and malignancy indicates a need to always evaluate for more than one cause of anemia. This study concludes that anemia in hospitalized patients of Palakkad is mainly severe in majority, where iron deficiency and microcytic pattern were found to be the major pattern. The severity was much connected to age and certain clinical and nutritional factors indicating the need for early identification and etiological assessment. Screening at community level, nutritional assessment, appropriate investigation of iron deficiency as well as chronic disease and timely treatment may help prevent severe anemia and late presentation in hospital.

   An etiological spectrum. Risk factors, severity of anemia among patients attending the Department of General Medicine, District Hospital Palakkad. Of more than 13 years of age was evaluated in this study. Iron deficiency anemia was the commonest etiology making up 63.8% of the cases, closely followed by anemia of chronic disease causing a lot of cases contributing about 13.3% of the total. Vitamin B12 deficiency was also an important cause of anemia in the population making up about 12.0% of the cases. Blood loss was also an important contributing cause of anemia. The high prevalence of severe anemia and the central relationship of severity with advancing age underscores the need for early recognition, proper etiological work-up, and treatment. Anemia and iron deficiency screening; nutritional assessment; diagnosis of chronic diseases and occult blood loss; and the administration of proper supplementation and treatment may address the burden of severe anemia and prevent complications. The current study gives valuable community-based information on etiological pattern, predisposing factors and severity of anemia in patients who attended district hospital, Palakkad. The findings may work as a basis for planning, designing, and reinforcing community-based screening and anemia controlling programs in the community. Further community studies in large numbers are needed to estimate the prevalence and the determinants of anemia in the community and to explore the efficiency of individual preventive and treatment measures in the control of anemia.