Background: Pancytopenia, defined by simultaneous reductions in hemoglobin, leukocytes, and platelets, poses a diagnostic challenge due to varied etiologies. Bone marrow examination remains a cornerstone for evaluation. This study aimed to characterize bone marrow morphological patterns in pancytopenia and correlate findings with clinical and hematological parameters. Methods: A prospective observational study was conducted on 100 patients presenting with pancytopenia. Detailed clinical evaluation, complete blood count (CBC), peripheral smear, and bone marrow aspiration and trephine biopsy were performed. Bone marrow patterns were categorized and correlated with clinical data. Results: The most common etiological categories were megaloblastic anemia (40%), aplastic anemia (20%), hypersplenism (12%), acute leukemia (10%), myelodysplastic syndromes (MDS) (6%), and miscellaneous causes (12%). Bone marrow cellularity and morphological patterns correlated significantly with clinical features and hematological indices. Megaloblastic changes were noted in 40 cases, hypocellularity in 20 cases, hypercellularity with blasts in 10 cases, and dysplastic features in 6 cases. Conclusion: Bone marrow examination is essential for diagnosing the underlying cause of pancytopenia. Megaloblastic anemia remains the leading cause in this cohort. Clinicopathological correlation enhances diagnostic accuracy and guides management.
Pancytopenia is defined by a reduction in all three major hematological cell lines: red blood cells, white blood cells, and platelets. It represents a manifestation of underlying bone marrow dysfunction or peripheral destruction/sequestration of blood cells. Common clinical presentations include fatigue, fever, bleeding tendencies, and infections[1]. The differential diagnoses are broad, ranging from nutritional deficiencies to malignant disorders. Accurate identification of etiology is crucial for effective management.
Bone marrow examination comprising aspiration and trephine biopsy is the definitive diagnostic tool for pancytopenia, facilitating the determination of cellularity, lineage dysplasia, infiltration, and fibrosis[2-3]. Although several studies have described individual causes of pancytopenia, comprehensive clinicopathological correlation remains essential to understand local patterns and guide health policy.
This study aimed to analyze bone marrow morphological patterns in patients with pancytopenia and correlate these findings with clinical presentations and laboratory parameters in a tertiary care setting[4-5].
A prospective observational study conducted over 18 months in the Departments of Pathology and Internal Medicine at a tertiary care hospital.
Inclusion Criteria
Exclusion Criteria
Data Collection
Detailed clinical history, physical examination, and laboratory parameters were recorded. Routine investigations included CBC with peripheral smear, reticulocyte count, liver and renal function tests, vitamin B12 and folate levels, and viral serology as indicated.
Bone Marrow Examination
Bone marrow aspiration and trephine biopsy were performed under aseptic conditions from the posterior superior iliac spine. Aspirates and biopsy sections were stained with May Grunwald Giemsa and hematoxylin eosin respectively. Special stains and immunohistochemistry were applied where necessary.
Statistical Analysis
Data were entered in Microsoft Excel and analyzed using SPSS v23. Descriptive statistics were expressed as mean ± SD or percentages. Chi-square test was used for categorical variables; p < 0.05 was considered statistically significant.
Demographics and Clinical Features
Of the 100 patients enrolled, 58 (58%) were male and 42 (42%) were female with a mean age of 38.5 ± 15.2 years (range 12–78 years). Fatigue (85%), pallor (80%), fever (42%), and bleeding manifestations (30%) were the common symptoms.
Table 1: Demographic and Clinical Profile (n = 100)
|
Variable |
n (%) |
|
Male |
58 (58) |
|
Female |
42 (42) |
|
Mean Age (Years) |
38.5 ± 15.2 |
|
Fatigue |
85 (85) |
|
Pallor |
80 (80) |
|
Fever |
42 (42) |
|
Bleeding |
30 (30) |
|
Splenomegaly |
25 (25) |
Hematological Parameters
The mean hemoglobin was 7.8 ± 1.5 g/dL, leukocyte count 2.8 ± 0.9 × 10^9/L, and platelet count 55 ± 22 × 10^9/L.
Table 2: Hematological Parameters (n = 100)
|
Parameter |
Mean ± SD |
|
Hemoglobin (g/dL) |
7.8 ± 1.5 |
|
Total Leukocyte Count (×10^9/L) |
2.8 ± 0.9 |
|
Platelet Count (×10^9/L) |
55 ± 22 |
|
MCV (fL) |
102.5 ± 12.4 |
|
Reticulocyte Count (%) |
0.8 ± 0.5 |
Bone Marrow Morphology
Bone marrow findings revealed varied patterns as shown below:
Table 3: Bone Marrow Morphological Patterns (n = 100)
|
Morphological Pattern |
N (%) |
|
Megaloblastic changes |
40 (40) |
|
Hypocellular marrow |
20 (20) |
|
Hypercellular with blasts |
10 (10) |
|
Dysplastic features |
06 (06) |
|
Normal/Reactive marrow |
12 (12) |
|
Infiltrative/Other |
12 (12) |
Etiological Correlation
The final etiological diagnoses were established by integrating clinical, hematological, and bone marrow findings.
Table 4: Etiological Distribution of Pancytopenia (n = 100)
|
Diagnosis |
N (%) |
|
Megaloblastic Anemia |
40 (40) |
|
Aplastic Anemia |
20 (20) |
|
Hypersplenism |
12 (12) |
|
Acute Leukemia |
10 (10) |
|
MDS |
06 (06) |
|
Others* |
12 (12) |
*Others include nutritional anemia with concomitant chronic disease (5), myelofibrosis (3), hemophagocytic syndrome (2), storage disorders (2)
Correlation of Bone Marrow Pattern with Clinical Features
Megaloblastic anemia patients commonly presented with macrocytosis and elevated MCV (> 100 fL), while aplastic anemia cases exhibited severe pancytopenia with hypocellular marrow (p < 0.001). Acute leukemia cases were associated with hypercellular marrow and blast predominance (p < 0.001).
Pancytopenia represents a hematological condition with broad etiologies, necessitating careful evaluation. In this study of 100 patients, megaloblastic anemia was the predominant cause (40%), consistent with several regional studies that report high prevalence due to nutritional deficiencies and malabsorption syndromes[6].
Megaloblastic Anemia
Megaloblastic changes were the most frequent bone marrow pattern. Patients typically had macrocytic indices, low reticulocyte count, and characteristic morphological features such as nuclear cytoplasmic asynchrony and giant metamyelocytes. Vitamin B12 and folate deficiencies accounted for most cases, underlining the need for nutritional assessment[7-8].
Aplastic Anemia
Aplastic anemia contributed to 20% of cases with hypocellular marrow, consistent with literature highlighting aplasia as a significant cause of pancytopenia[9]. Etiologies included idiopathic aplasia, drug-induced marrow suppression, and viral infections.
Hypersplenism
Hypersplenism accounted for 12% of cases. Clinical examination often revealed splenomegaly. Bone marrow in hypersplenism usually appears normocellular or mildly hypercellular, with peripheral destruction causing cytopenias[10].
Acute Leukemia and MDS
Acute leukemia (10%) and MDS (6%) comprised clonal marrow disorders. The characteristic hypercellular marrow with blast cells or dysplastic features underscores the importance of morphology and immunophenotyping for diagnosis[11].
Miscellaneous Etiologies
The “Others” category included rare disorders such as myelofibrosis, storage disorders, and hemophagocytic syndrome, highlighting the diversity of pathological processes resulting in pancytopenia.
Clinical Correlation and Management Implications
The integration of clinical features with bone marrow morphology enabled accurate diagnosis and informed treatment strategies. For instance, early identification of acute leukemia facilitated prompt chemotherapy, whereas megaloblastic anemia required nutritional supplementation and monitoring[12].
While the sample size was adequate, advanced molecular studies (e.g., cytogenetics for MDS) were not uniformly available. Follow-up data on treatment outcomes were beyond study scope.
Bone marrow examination remains pivotal in the evaluation of pancytopenia. This study emphasizes that megaloblastic anemia is the most common cause in this cohort, followed by aplastic anemia and hypersplenism. Thorough clinicopathological correlation enhances diagnostic precision and patient management