European Journal of Cardiovascular Medicine

Pancytopenia is a hematological condition characterized by a concurrent reduction in all three major blood cell lines erythrocytes, leukocytes, and platelets resulting in anemia, leucopenia, and thrombocytopenia, respectively [1]. It is not a disease entity by itself but a manifestation of diverse underlying disorders that affect the bone marrow through mechanisms such as suppression, failure, or infiltration. The clinical impact of pancytopenia varies widely, ranging from mild cytopenias detected incidentally to severe life-threatening infections and hemorrhagic episodes, depending on the degree and rapidity of marrow dysfunction [2].

The etiological profile of pancytopenia differs across regions and populations due to variations in nutritional habits, environmental exposure, and infectious disease prevalence. In developing countries such as India, megaloblastic anemia secondary to deficiencies of vitamin B₁₂ and folate remains the leading cause, whereas aplastic anemia, myelodysplastic syndromes, leukemias, and marrow infiltrative disorders account for major non-nutritional causes [3,4]. Infectious conditions, particularly malaria, leishmaniasis, and viral infections, also play a significant role in endemic zones, emphasizing the need for regional data to guide diagnosis and treatment [5].

Peripheral blood smear and bone marrow examinations continue to serve as the cornerstone of diagnostic evaluation in pancytopenia. The peripheral smear provides early morphological clues, while bone marrow aspiration and trephine biopsy confirm the diagnosis and reveal the extent and nature of marrow involvement [1,4]. Correlating these hematological parameters with clinical presentation allows for early recognition, appropriate therapeutic intervention, and improved patient outcomes.

Given the heterogeneity of causes and their prognostic implications, it is essential to study the pattern and frequency of various etiologies in local populations. The present observational study was undertaken to analyze the peripheral blood and bone marrow findings in patients with pancytopenia, to determine the underlying hematological disorders, and to highlight the importance of marrow evaluation in accurate etiological diagnosis.

Study Design and Duration

This was a hospital-based observational study conducted over a period of six months, from May to October 2023, in the Department of Pathology, Government General Hospital, Eluru, Andhra Pradesh, India. The study aimed to evaluate the peripheral blood and bone marrow findings in patients presenting with pancytopenia.

Study Population

A total of 50 patients of all age groups and both sexes who were clinically suspected and hematologically confirmed to have pancytopenia were included. All patients were referred to the hematology section of the pathology department for bone marrow examination during the study period.

Inclusion Criteria

Patients with hemoglobin <10 g/dL,

Total leukocyte count <4,000/mm³, and

Platelet count <100,000/µL,
were considered to have pancytopenia and included in the study.

Exclusion Criteria

Patients who had received recent chemotherapy or radiotherapy,

Those with known hypersplenism or chronic liver disease, and

Incomplete clinical or laboratory data cases were excluded.

Data Collection and Investigations

Detailed clinical history and physical examination findings were recorded for each patient. Venous blood samples were collected under aseptic precautions and analyzed using an automated hematology analyzer for complete blood counts. Peripheral blood smears were prepared and stained with Leishman and Giemsa stains to assess red cell morphology, leukocyte distribution, and platelet estimation.

Bone marrow aspiration was performed from the posterior superior iliac spine or sternum, and trephine biopsy was obtained in selected cases. The smears were stained with Leishman, Giemsa, and Perls’ Prussian blue stains (for iron stores), while biopsy sections were processed and stained with hematoxylin and eosin. Each bone marrow sample was evaluated for cellularity, erythroid and myeloid series, megakaryocytes, dysplasia, fibrosis, and infiltration by abnormal or malignant cells.

Statistical Analysis

Data were entered in Microsoft Excel and analyzed using SPSS version 25.0. Descriptive statistics were used to summarize clinical and hematological parameters. The frequency and percentage distributions of different etiological categories were calculated, and the correlation between peripheral smear morphology and bone marrow findings was assessed.

Ethical Considerations

Prior approval for the study was obtained from the Institutional Ethics Committee, Government General Hospital, Eluru. Informed written consent was taken from all participants before inclusion in the study.

A total of 50 patients presenting with pancytopenia were evaluated through comprehensive hematological and bone marrow analysis. The age of the patients ranged from 8 to 72 years, with a mean age of 38.4 ± 14.6 years. The maximum incidence (40%) was observed in the 21–40-year age group, followed by 32% in the 41–60 years category. Males constituted 60% of cases, whereas females accounted for 40%, yielding a male-to-female ratio of 1.5:1 (Table 1).

Table 1. Demographic and Clinical Characteristics of Patients with Pancytopenia (n = 50)

The most frequent clinical presentations included pallor (100%), generalized weakness (84%), and fever (62%). Other manifestations such as bleeding tendencies (20%), hepatosplenomegaly (26%), and lymphadenopathy (12%) were also recorded (Table 1). These findings highlight that generalized weakness and pallor remain consistent features across all etiologies of pancytopenia.

The hematological indices of the patients are summarized in Table 2. The mean hemoglobin level was 6.9 ± 1.8 g/dL, indicating severe anemia in most cases. The total leukocyte count ranged from 1,200 to 3,900 cells/mm³, while platelet counts varied between 20 × 10³ to 110 × 10³/µL (mean = 56.4 ± 22.1 × 10³/µL). The mean corpuscular volume (MCV) was 93.6 ± 14.2 fL, suggesting a predominance of macrocytosis (Figure 1).

Table 2. Hematological Parameters in Pancytopenic Patients

Figure 1. Hematological Parameters in Pancytopenic Patients

Peripheral blood smear examination (Table 3) demonstrated macrocytic anemia as the most common pattern (36%), followed by normocytic normochromic anemia (28%), microcytic hypochromic anemia (20%), and dimorphic picture (16%). The macrocytic picture strongly correlated with megaloblastic marrow morphology (Figure 2).

Table 3. Peripheral Blood Smear Findings

Figure 2. Peripheral Blood Smear Findings

Bone marrow aspiration and biopsy findings (Table 4) revealed megaloblastic anemia as the leading etiology (36%), followed by aplastic anemia (20%) and hypoplastic marrow (12%). Less frequent causes included acute leukemia (10%), myelodysplastic syndrome (8%), malarial or leishmanial infiltration (6%), and lymphomatous infiltration (4%).

Table 4. Bone Marrow Examination Findings

A notable correlation was observed between the macrocytic peripheral smear and megaloblastic marrow changes, while normocytic smears frequently corresponded to aplastic or hypoplastic marrow. Leukoerythroblastic reactions in five cases were associated with marrow infiltration by malignant cells.

Following diagnosis, 68% of patients showed hematological recovery after appropriate treatment (vitamin supplementation, immunosuppressants, or disease-specific therapy), while 12% had persistent cytopenias on follow-up. The mortality rate (8%) was primarily seen among those with aplastic anemia and acute leukemia.

Pancytopenia represents a significant diagnostic challenge due to its broad etiological spectrum and variable clinical presentation. Its evaluation requires an integrated assessment of clinical features, peripheral smear morphology, and bone marrow findings to establish an accurate diagnosis and guide effective management [6,7]. The present study, conducted at Government General Hospital, Eluru, from May to October 2023, analyzed 50 patients with pancytopenia to delineate the underlying hematological causes and their morphological correlations.

In this series, the mean age was 38.4 years, with the highest incidence (40%) observed in the 21–40-year age group, indicating that pancytopenia predominantly affects young and middle-aged adults—a trend similar to that reported in Central Indian and South Asian studies [8,10,11]. The male predominance (M:F = 1.5:1) noted in our study aligns with previous research demonstrating higher prevalence among males, likely reflecting nutritional disparities and occupational exposure risks [6,9].

Clinically, pallor (100%), generalized weakness (84%), and fever (62%) were the most common presentations, consistent with prior observations by Varma et al. and Zubair et al., where nonspecific constitutional symptoms predominated in the initial stages of marrow failure [6,11]. Bleeding manifestations (20%) and hepatosplenomegaly (26%) also correspond to findings from Yokuş and Gedik, emphasizing that clinical manifestations may vary according to etiology and chronicity of marrow suppression [7].

Peripheral smear evaluation revealed macrocytic anemia (36%) as the predominant pattern, correlating strongly with megaloblastic marrow changes (36%), which constituted the most frequent etiology in this study. This association supports earlier findings that megaloblastic anemia remains the leading and potentially reversible cause of pancytopenia in developing regions [9,10]. The high prevalence of vitamin B₁₂ and folate deficiency in low-resource settings reinforces the need for nutritional screening as an initial diagnostic approach [11].

Aplastic anemia (20%) and hypoplastic marrow (12%) represented the next major etiological groups, comparable with results reported by Gayathri and Rao and Shah et al., where marrow hypoplasia accounted for a substantial proportion of non-nutritional pancytopenia cases [8,9]. Furthermore, acute leukemia (10%) and myelodysplastic syndromes (8%) were notable causes, reflecting the contribution of clonal marrow disorders in adult patients [12]. Infectious etiologies, such as malaria and visceral leishmaniasis (6%), though less common, remain clinically relevant in endemic regions as reversible causes of marrow suppression [10].

The correlation between macrocytic smears and megaloblastic marrow and between normocytic smears and aplastic/hypoplastic marrow, observed in our cohort, is consistent with the diagnostic trends reported in earlier studies [8,9,12]. Such morphological alignment between peripheral blood and marrow findings strengthens diagnostic precision and aids in prioritizing specific investigations, especially in resource-limited setups.

In summary, the findings of the present study parallel those of major regional and international reports [6–12], reaffirming that megaloblastic anemia remains the most common and treatable cause of pancytopenia, while aplastic anemia and marrow dyscrasias constitute significant non-nutritional etiologies. A systematic diagnostic approach combining clinical evaluation, hematological parameters, and bone marrow assessment remains indispensable for early identification, effective treatment, and improved patient outcomes.

Limitations

The study was limited by its small sample size and single-center design, which may restrict generalizability. Advanced investigations such as cytogenetic and molecular studies were not performed, potentially overlooking subtle marrow abnormalities and secondary causes of pancytopenia

The present study highlights that pancytopenia is a manifestation of varied hematological disorders, with megaloblastic anemia emerging as the most common and reversible cause, followed by aplastic anemia, hypoplastic marrow, and acute leukemia. The correlation between peripheral smear morphology and bone marrow findings underscores the importance of thorough hematological evaluation in establishing the underlying etiology. Early identification through simple diagnostic tools such as peripheral smear and bone marrow aspiration facilitates timely therapeutic intervention, reducing morbidity and mortality. A comprehensive approach integrating clinical features and cytomorphological findings remains crucial for accurate diagnosis and effective management of patients presenting with pancytopenia.

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