European Journal of Cardiovascular Medicine

Pancytopenia is defined as the simultaneous reduction in all three major cellular components of the peripheral blood: erythrocytes, leukocytes, and platelets. It is a triad that can arise from a wide range of disease processes and is often a clinical indicator of serious underlying pathology. While not a diagnosis in itself, pancytopenia reflects bone marrow failure, peripheral destruction, or sequestration of hematopoietic elements and necessitates detailed evaluation to identify the root cause [1].

The condition has significant clinical implications and may present with symptoms such as anemia, fever, bleeding tendencies, and susceptibility to infections. Its etiological spectrum varies widely across geographical and demographic contexts, influenced by factors such as age, nutritional status, socioeconomic conditions, and the prevalence of infections and hematologic malignancies [2,3].

In developing countries, nutritional deficiencies, particularly megaloblastic anemia, are among the most common causes of pancytopenia, whereas in developed countries, hematological malignancies and aplastic anemia are more prevalent [4,5]. Other contributory causes include viral infections (e.g., HIV, hepatitis), drug toxicity, autoimmune diseases, hypersplenism, and infiltrative disorders such as leukemia or lymphoma [6,7].

The pathophysiology of pancytopenia may involve either a reduction in hematopoietic cell production (due to bone marrow hypoplasia, infiltration, or suppression), ineffective hematopoiesis (e.g., in megaloblastic anemia), or peripheral destruction/sequestration of blood cells (e.g., hypersplenism) [8,9]. Bone marrow examination remains a cornerstone in the diagnostic workup of pancytopenia, providing valuable insights into marrow cellularity, maturation arrest, dysplastic changes, and malignant infiltration [10,11].

Early diagnosis and identification of the underlying etiology are crucial, as treatment strategies vary significantly—from vitamin supplementation in nutritional anemia to chemotherapy in malignancies or immunosuppressive therapy in aplastic anemia. Despite its frequency in clinical practice, comprehensive regional data on pancytopenia remains limited, especially from central India.

This study was undertaken to evaluate the clinical presentation, hematological parameters, and bone marrow findings in patients with pancytopenia presenting to a tertiary care hospital. Understanding these patterns can aid in the timely diagnosis and management of affected individuals.

Study Design and Setting

This descriptive observational study was conducted at the Department of Pathology, Pt. J.N.M. Medical College and the associated Dr. B.R.A.M. Hospital, Raipur (Chhattisgarh), over a period of one year from April 2014 to March 2015.

Sample Size and Selection Criteria

A total of 96 patients presenting with pancytopenia were included in the study. These patients belonged to the age group of 2–71 years and represented both sexes. Patients were selected based on strict inclusion and exclusion criteria.

Inclusion Criteria

Newly diagnosed cases of pancytopenia were included as per the definition provided by de Gruchy [1]:

• Hemoglobin: <13.5 gm/dL (males), <11.5 gm/dL (females)
• Total leukocyte count (TLC): <4000/mm³
• Platelet count: <150,000/mm³

Exclusion Criteria

• Patients with a recent history of blood transfusion
• Patients undergoing chemotherapy or radiotherapy for malignancies

Data Collection

From all bone marrow aspiration procedures performed in the clinical pathology section, those ordered specifically for pancytopenia were selected. For each included case:

• A detailed clinical history was recorded using a standardized questionnaire.
• Thorough physical and systemic examinations were conducted.
• Emphasis was given to symptoms like bleeding tendencies (epistaxis, melena, hematuria, hematemesis), recent infections, and drug history including anti-malarials and anti-tuberculous medications.

Hematological Investigations

All patients underwent complete hematological evaluation:

• Hemoglobin, TLC, platelet count, and red cell indices including mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were measured using an automated hematology analyzer.
• Peripheral blood smear examinations were performed and stained using Leishman stain to cross-check automated results and to evaluate red blood cell morphology, leukocyte abnormalities, and platelet estimates.

Bone Marrow Examination

Bone marrow aspirations were performed in all 96 cases and were evaluated for:

• Marrow cellularity
• Megakaryocyte status
• Myeloid-to-erythroid ratio
• Presence of abnormal cells or infiltrates
• Dysplastic changes in hematopoietic lines

The bone marrow findings were correlated with peripheral smear results and the clinical presentation to arrive at the etiological diagnosis.

Statistical Analysis

The collected data were statistically analyzed to determine:

• Age and sex distribution
• Presenting symptoms and clinical signs
• Hematological and morphological parameters
• Final etiological diagnosis

Comparisons were made with previously published studies to identify trends in clinical presentation and disease patterns in pancytopenic patients

Demographic Profile
Out of the 96 patients included in this study, the most affected age group was 15–30 years, with 59 cases (61%) occurring in the second and third decades of life. The overall male-to-female ratio was 1.3:1, indicating a slight male predominance (Table 1 and 2).

Clinical Presentations
All patients presented with generalized weakness (100%), followed by fever in 45%, and bleeding tendencies in a minority (Table 3). On clinical examination, pallor was noted in all patients (100%), followed by splenomegaly (47%), hepatomegaly (38%), and lymphadenopathy in a few (Table 4).

Hematological Parameters

• Hemoglobin levels were predominantly between 6–9 g/dL in 50% of patients (Table 5).
• The total leukocyte count ranged between 2000–3000 cells/mm³ in the majority of cases (Table 6).
• Platelet counts were found to be in the range of 50,000–100,000 cells/mm³ in most patients (Table 7).
• Bleeding tendencies correlated with lower platelet counts; patients with platelet counts <50,000/mm³ showed a higher frequency of bleeding symptoms (Table 8).
• Peripheral smear analysis revealed a predominance of macrocytic and dimorphic anemia patterns (Table 9).

Bone Marrow Findings
Bone marrow aspiration showed varied cellularity:

• Hypercellular marrow was observed predominantly in cases of megaloblastic anemia.
• Hypocellular marrow was associated with aplastic anemia.
• Normocellular marrow was seen in dimorphic anemia and hypersplenism cases (Table 10).

Etiological Spectrum
The most common underlying cause was megaloblastic anemia, diagnosed in 39% of patients, followed by hypersplenism (12%) and dimorphic anemia (12%) (Table 11). Other causes included:

• Acute leukemia: 10 cases (10%)
• Iron deficiency anemia: 8 cases (8%)
• Aplastic anemia: 4 cases (4%)
• Non-Hodgkin’s lymphoma: 4 cases (4%)
• Immune thrombocytopenic purpura (ITP): 4 cases (4%)
• Micronormoblastic erythropoiesis: 3 cases
• Multiple myeloma: 2 cases
• Hypoplastic marrow without definitive diagnosis: 2 cases

The study analyzed the clinical and hematological findings of 96 patients diagnosed with pancytopenia, with a focus on bone marrow morphology and peripheral blood smears.

1. Age and Sex Distribution
   The most affected age group was between 12–21 years (45 patients, 47%), followed by 22–31 years (20 patients, 21%), and 2–11 years (10 patients, 10%). The male-to-female ratio was 1.3:1, with 57% of the patients being male and 43% female.
2. Clinical Symptoms
   All patients exhibited generalized weakness (100%), with fever (45%), and loss of appetite (~50%) being common symptoms. Cough, weight loss, and other minor symptoms were observed in a smaller percentage of patients.
3. Hematological Findings

• Hemoglobin Levels: A majority of patients had hemoglobin levels between 6–9 g/dL (50% of the cases), indicating moderate-to-severe anemia.
• Platelet Count and Correlation with Bleeding: Platelet counts less than 50,000/mm³ were correlated with increased bleeding tendencies, further highlighting the significant role of low platelet count in the manifestation of bleeding symptoms.
• Leukocyte Count: A majority of patients had a leukocyte count between 2,000–3,000/mm³, suggesting an overall decrease in white blood cells, a hallmark of pancytopenia.

4. Bone Marrow Findings

• Megaloblastic Anemia: The most common diagnosis in the study was megaloblastic anemia (39%), where the bone marrow revealed hypercellularity with large, abnormal erythroid precursors or megaloblasts. Hypersegmented neutrophils were also observed in peripheral smears, confirming the diagnosis.
• Hypersplenism and Dimorphic Anemia: Hypersplenism (12%) and dimorphic anemia (12%) were the next most frequent causes. Bone marrow aspiration in these cases showed normocellular marrow for hypersplenism, while dimorphic anemia cases showed a mix of microcytic and macrocytic red blood cells.
• Aplastic Anemia and Acute Leukemia: Other causes, such as aplastic anemia (4%) and acute leukemia (10%), were also observed, with the bone marrow showing hypocellularity and blasts (immature cells) respectively.

5. Etiology
   The study revealed that the leading cause of pancytopenia was megaloblastic anemia (39%), followed by hypersplenism (12%), dimorphic anemia (12%), and acute leukemia (10%). Other less common causes included iron deficiency anemia (8%), aplastic anemia (4%), multiple myeloma (2%), and non-Hodgkin's lymphoma (4%).

TABLES, GRAPHS AND DIAGNOSTIC IMAGES

Table -01     Age At Presentation

Figure 1

Table-02      Sex Distribution Of Patients With Pancytopenia

Table -03      Symptoms Of Patient With Pancytopenia

Table -04     Clinical Sign of Patient with Pancytopenia

Table-05      Haemoglobin Level In Patient With Pancytopenia

Table-06      Total Leukocyte Count In Patient With Pancytopenia

Table-07     Platelet Count In Patient With Pancytopenia

Table-08      Platelet Count and It’s Correlation with Bleeding Tendencies in Patient with Pancytopenia

Table-09     Red Blood Cell Morphology on Peripheral Smear In Patients With Pancytopenia

Table-10     Bone Marrow Cellularity In Patient With Pancytopenia

Table-11      Etiology of Pancytopenia in Study Population

MEGALOBLASTIC ANEMIA

Photomicrograph of peripheral smear showing macroovalocyte hypersegmented neutrophil in megaloblastic anemia (40 x)

•                                                                                   (B)

Photomicrograph of bone marrow aspirate smear showing normoblast having megaloblastoid changes (A ) and megaloblast  with royal blue cytoplasm and sieve like chromatin in megaloblastic anemia(B)

DIMORPHIC ANEMIA

Photomicrograph of peripheral smear showing dual population of microcytic hypochromic red cells and well hemoglobinized macrocytes in dimorphic anemia

Photomicrograph of bone marrow aspirate showing cluster of late micronormoblast and early megaloblast with large size having royal blue cytoplasm of dimorphic anemia

IRON DEFICIENCY ANEMIA

Photomicrograph of peripheral smear showing microcytic hypochromic picture with tear drop cell, pencil cell in Iron deficiency anemia

Photomicrograph of bone marrow aspiration smear showing micronormoblastic hyperplasia in iron deficiency anemia

ACUTE LEUKAEMIA

Photomicrograph of bone marrow aspirate showing sheets of small, uniform sized monomorphous blasts in acute leukemia

MULTIPLE MYELOMA

Photomicrograph of bone marrow aspirate showing plasma cell with eccentric nuclei, basophilic cytoplasm  and few binucleated plasma cell in multiple myeloma

APLASTIC ANEMIA

Photomicrograph of bone marrow aspirate showing hypocellularity with increased fat and reactive lymphoplasmacytosis in Aplastic anemia

NON-HODGKIN’S LYMPHOMA

Photomicrograph of bone marrow aspirate showing sheets of predominance of large blast with irregular nucleus ,abnormal chromatin , prominent nucleoli with surrounding  normal hemopoitic cell in Non-hodkin’s lymphomaA

Pancytopenia, a condition characterized by the simultaneous reduction of all three blood cell lines—erythrocytes, leukocytes, and platelets—is not a disease by itself but a manifestation of several underlying disorders. This condition is often associated with serious and life-threatening illnesses, and extensive studies have been conducted to identify its various etiologies, such as megaloblastic anemia, aplastic anemia, leukemia, and hypersplenism. However, there is a paucity of comprehensive studies that explore the clinico-hematological spectrum of pancytopenia in the Indian context.

In the present study, we focused on the evaluation of pancytopenia in a cohort of 96 patients who underwent bone marrow aspiration for diagnosis. The bone marrow examination (BME) for pancytopenia was indicated in 42% of the cases, which is consistent with findings from previous Indian studies. For example, in a study by Niazi et al. (2004) [3], BME for pancytopenia was performed in 19% of cases, while Bashawri et al. (1999) [7] reported a frequency of 11.9%. Our study observed a higher percentage of BME requests, suggesting that pancytopenia remains a significant clinical concern that requires thorough investigation.

The age distribution of pancytopenia in our study revealed that the most commonly affected group was between 15–30 years, a finding consistent with studies by Kishore et al. [6], Khunger et al. [3], and Tilak et al. [14], where a similar pattern of incidence was noted in the first three decades of life. The overall male-to-female ratio in our study was 1.3:1, which is also comparable to the findings of Khodke et al. [15], who reported a male predominance of 1.3:1. These findings are consistent with the general trend observed in many studies conducted across India, where males are more frequently affected by pancytopenia.

In terms of clinical presentation, generalized weakness was reported by all patients (100%) in our study, followed by fever in 45% of the cases. These findings are in line with Tilak et al. [14], who also identified generalized weakness as the predominant symptom in pancytopenic patients. Additionally, physical examination revealed pallor (100%), splenomegaly (47%), and hepatomegaly (38%) in the majority of patients, which aligns with the findings of Santra et al. [20], where splenomegaly and hepatomegaly were commonly observed.

The most frequent etiology of pancytopenia in our cohort was megaloblastic anemia (39%), consistent with other Indian studies by Tilak et al. [14] and Khodke et al. [15], where megaloblastic anemia was also found to be the leading cause of pancytopenia. However, in our study, the serum folic acid and vitamin B12 levels were not assessed, which could have further refined the diagnosis. Despite the lack of specific tests, bone marrow aspiration proved to be instrumental in diagnosing megaloblastic anemia, particularly in settings where hematological assays are not readily available. The high prevalence of nutritional deficiencies in the region likely contributes to the prominence of megaloblastic anemia.

Hypersplenism (12%) and dimorphic anemia (12%) were the second most common causes of pancytopenia in our study. These findings are consistent with Fahim Manzoor et al. [21], who noted hypersplenism as the third most common cause in their study. Hypersplenism is often seen in patients with chronic liver disease or cirrhosis, where the spleen becomes enlarged and sequesters blood cells. The increasing prevalence of chronic alcoholism may contribute to the rising incidence of hypersplenism, which is a consequence of liver dysfunction.

Another notable finding in our study was the detection of acute leukemia in 10% of the pancytopenic patients, with the majority of cases occurring in the <14-year age group. This was consistent with the study by Kumar et al. [26], which found acute leukemia in 9% of cases. Iron deficiency anemia, which is another well-known cause of pancytopenia, was found in 8% of our patients, consistent with findings from Anita P. et al. [17] and Osama Ishtiaq et al. [27], who observed iron deficiency in 5% of pancytopenic patients. The exact mechanism by which iron deficiency leads to pancytopenia is unclear but is thought to be related to impaired hematopoiesis due to the lack of essential iron for normal blood cell production.

In addition to the more common causes, our study also identified immune thrombocytopenic purpura (ITP), non-Hodgkin’s lymphoma (NHL), and aplastic anemia in smaller numbers of patients. These findings are consistent with the diverse etiological spectrum of pancytopenia reported by other studies, including Rajendra Kumar Nigam et al. [13] and Manzoor F et al. [21].

Comparisons of hematological parameters such as hemoglobin levels, total leukocyte count, and platelet counts showed that the majority of our patients had hemoglobin levels between 6–9 g/dL (50%), a total leukocyte count between 2000–3000 cells/mm³ (60%), and platelet counts between 50,000–100,000 cells/mm³ (50%). These results are in line with other studies, such as Priyank Modi et al. [4], who observed similar distributions of hemoglobin and leukocyte counts.

In conclusion, pancytopenia remains a diagnostic challenge with multiple underlying causes, many of which are influenced by regional factors such as nutritional deficiencies and infectious diseases. The findings from this study underscore the importance of bone marrow examination as a vital diagnostic tool for evaluating pancytopenia, especially when clinical or laboratory findings are inconclusive. Early identification of the underlying cause is crucial for guiding appropriate treatment strategies, ranging from nutritional interventions for megaloblastic anemia to chemotherapy for leukemia.

Pancytopenia is a critical hematological condition with a broad spectrum of underlying etiologies, many of which are life-threatening. This study highlights the importance of bone marrow examination (BME) as a vital diagnostic tool in identifying the causes of pancytopenia. The most common etiology identified was megaloblastic anemia, followed by hypersplenism and dimorphic anemia, with a significant portion of patients presenting with generalized weakness, fever, and splenomegaly. Early recognition of the underlying cause through clinical and hematological assessments is essential to guide appropriate treatment strategies. The findings underscore the high prevalence of nutritional deficiencies and infectious causes, particularly in developing countries. The results emphasize the need for adequate diagnostic protocols and the importance of regional studies to understand and manage pancytopenia effectively, ensuring timely intervention for better patient outcomes

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