Clinical Profile of Patients with Pancytopenia at a Tertiary Care Hospital

Introduction

Pancytopenia is characterized by the concurrent reduction of erythroid, myeloid, and megakaryocytic cellular components, leading to anemia, leucopenia, and thrombocytopenia. It is not classified as a distinct disease but rather a combination of findings that arise from several disease processes affecting the bone marrow [1]. The incidence of disorders that lead to pancytopenia varies according to geographic and genetic factors. It is associated with a range of serious conditions, from drug-induced bone marrow hypoplasia and megaloblastic anemia to severe situations like bone marrow aplasia and leukemia. Clinical manifestations, treatment approaches, and patient outcomes exhibit variability, with severity and underlying pathology influencing management and prognosis.

Hematopoiesis in healthy adults occurs primarily in the bone marrow, which serves as both a site for mature blood cell development and a dynamic reservoir. Blood cells migrate from the bone marrow into the circulation, spleen, and other areas. The bone marrow adapts to the body's ongoing demand for blood cell production, ensuring a delicate balance is maintained among the production, distribution in various organs, and destruction of blood cells. This balance is influenced by factors such as white blood cells combating infections, platelet usage in blood clots, and the natural aging of cells (cellular senescence) [2][4].

The study defines pancytopenia criteria based on De Gruchy's parameters: hemoglobin levels below 13.5 gm% in males and 11.5 gm% in females, white blood cell (WBC) counts under 4000 cells/mm³, and platelet counts below 150,000/mm³. Pancytopenia can arise from various mechanisms [5]: 1. Bone Marrow Infiltration: This includes hematologic malignancies such as leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes, metastatic cancer, and infectious diseases like miliary tuberculosis and fungal infections. 2. Bone Marrow Aplasia: Causes include nutritional deficiencies (vitamin B12 or folate), aplastic anemia, diseases (HIV, viral hepatitis, parvovirus B19), immune destruction, and certain medications. 3. Blood Cell Destruction or Sequestration: Excessive destruction may occur in conditions like disseminated intravascular coagulation and thrombotic thrombocytopenic purpura, while excessive sequestration can be attributed to hypersplenism related to liver cirrhosis, storage diseases, lymphoma, or autoimmune disorders [6][7].

The diagnosis of pancytopenia typically involves complete blood counts, peripheral smear analysis, and often a bone marrow examination. Additional tests such as abdominal and pelvic ultrasonography, serum ferritin, and serum vitamin B12 levels aid in identifying the underlying cause. Treatment begins with determining the etiology and involves a range of initial tests based on the patient’s symptoms. Symptomatic management is provided until a definitive diagnosis is established. Treatment plans are tailored to the underlying cause: cancer patients may receive chemotherapy or radiotherapy, while those with megaloblastic anemia are treated with cyanocobalamin supplementation. The study examines the clinical profile of pancytopenia patients at a tertiary care hospital, focusing on demographic characteristics, symptoms, clinical findings, and hematological parameters. It highlights the importance of diagnosing reversible causes, such as nutritional deficiencies and infections, versus conditions like aplastic anemia and hematological malignancies, necessitating urgent specialist intervention for better therapeutic outcomes.

To investigate the clinical profile of patients presenting with pancytopenia, this study aims to evaluate various hematological parameters associated with its causes and identify the underlying etiology of this condition.

Methods

The study was a descriptive observational study conducted at a tertiary care hospital in central India over 18 months focusing on all new cases of patients aged over 18, regardless of gender, who consulted the OPD/IPD Department of Medicine, Govt. Medical College, Nagpur. Participants were included based on the De Gruchy criteria, which required a hemoglobin level of less than 13.5 gm% for males and less than 11.5 gm% for females, a white blood cell (WBC) count of less than 4000 cells/mm³, and platelet counts below 150,000/mm³. Exclusion criteria included patients undergoing treatment with anticancer drugs or radiotherapy, those receiving bone marrow suppressing drugs, and individuals already diagnosed with pancytopenia under treatment. Methodologically, eligible patients underwent comprehensive medical history assessments and clinical examinations, followed by a range of laboratory investigations designed to uncover the causes of pancytopenia. These investigations included hemograms, liver function tests, kidney function tests, abdominal and pelvic ultrasounds, bone marrow examinations or aspiration biopsies, and potentially flow cytometry and hepatitis viral profiling as necessary. Additional tests were performed based on each patient's unique history and examination findings, including ESR via the Westergren method, urine and stool analyses, and ELISA tests for HIV, hepatitis B, and C viruses, along with chest and bone radiographs, urine Bence Jones proteins, and serum electrophoresis when indicated.

Results

Pancytopenia was predominantly observed in a study involving 92 patients, with a male-to-female ratio of 60.9% to 39.1%. The mean age was 35.88 ± 14.69 years, with the largest age group being 21 to 30 years (30% of patients), and 16% were under 20 years of age. The most common symptoms reported included easy fatigability (85.8%), generalized weakness (80.4%), fever (43.4%), and bleeding manifestations (33.7%). Clinical examinations revealed that pallor was observed in all patients (100%), followed by splenomegaly (53.2%), icterus (46.7%), and edema of feet (13%). Additionally, knuckle pigmentation was present in 44% of cases (Table 1).

In our study, 28% of the patients were identified as alcoholic, while 72% were non-alcoholic. A significant correlation was observed between alcoholism and megaloblastic anemia; specifically, out of 26 alcoholic patients with pancytopenia, 21 were diagnosed with megaloblastic anemia. Among the 92 pancytopenic patients, 48 were vegetarian and 44 were non-vegetarian. However, our findings indicated no significant correlation between diet and the various causes of pancytopenia. Megaloblastic anemia was found to be equally prevalent in both vegetarian and non-vegetarian groups (Table 2).

The study revealed a mean hemoglobin concentration of 5.4 g%, with specific findings of 5.19 g% in megaloblastic anemia, 5.43 g% in dimorphic anemia, and 5.37 g% in aplastic anemia. The mean WBC count was 2329.83/mm3, highest in hematological malignancies (2745/mm3) and lowest in aplastic anemia (1960/mm3). Mean platelet counts averaged 52126/mm3, with aplastic anemia patients showing the lowest at 50,500/mm3 and hypersplenism patients the highest at 67,428/mm3. The average Mean Corpuscular Volume (MCV) was 85.27 fl, with the highest MCV in megaloblastic anemia (95.39 fl) and the lowest in hypersplenism (74.49 fl). Aplastic anemia patients also exhibited a higher MCV (94.2 fl) (Table 3).

The study's peripheral smear analysis revealed that 42.39% of smears were dimorphic, while 29.35% exhibited macrocytic features. Additionally, 16.3% showed a microcytic picture, and 11.96% displayed a normocytic blood profile. In terms of bone marrow assessment, 60.8% were hypercellular, 21.7% demonstrated normal cellularity, and 11.96% were hypocellular. These findings highlight significant variability in peripheral smear and bone marrow cellularity among the subjects.

In a study of 92 patients, 44 were diagnosed with megaloblastic anemia, comprising 30 males and 14 females, with a mean age of 37.8 years. All patients exhibited pallor, and alcoholism was significantly correlated, as 21 out of 26 alcoholic subjects with pancytopenia were diagnosed with this type of anemia. The mean hemoglobin level for these patients was 5.19 g%, with a mean white blood cell (WBC) count of 2469/mm³ and mean platelet count of 53739/mm³. The average mean corpuscular volume (MCV) was 95.3 fl. Additionally, 10 patients had aplastic anemia, consisting of 1 male and 9 females, with a mean age of 47.6 years. Among these, 8 were vegetarians and 2 were non-vegetarians; however, no significant correlation between alcoholism and aplastic anemia was noted. All patients presented with generalized weakness and pallor, with a mean hemoglobin of 5.3 g%, mean WBC of 1960/mm³, and mean platelet count of 50500/mm³. The average MCV was 94.2 fl. Furthermore, 21 patients were identified with dimorphic anemia, which included 13 males and 8 females, with a mean age of 32.9 years. Out of these, 14 were non-vegetarians and 7 vegetarians, and 2 were alcoholic while 19 were non-alcoholic, with no significant correlation found between alcoholism and dimorphic anemia. All presented with generalized weakness and pallor, with a mean hemoglobin level of 5.4 g%, mean WBC count of 2481/mm³, and mean platelet count of 62810/mm³; the average MCV was 87.5 fl (Table 5).

Discussion

In the analyzed study, the mean age of patients was 35.88 ± 14.69 years, with the largest percentage (30%) falling within the 21-30 years age group. Additionally, 16% of the patients were younger than 20 years. This finding aligns with a study by Haridas et al.,[8] which also reported a concentration of patients in the 21-30 years age bracket. Conversely, a different study by Dhooria et al.,[9] indicated a higher mean age of 45.69 ± 17.05 years, with the greatest number of patients (23%) being aged 51-60 years. Similarly, research conducted by Khan et al.,[10] reaffirmed that the majority of patients were in the 21-30 years age group. Overall, these studies consistently suggest that the 21-30 years age range is the most prevalent among patients.

In our study of pancytopenia, a notable gender distribution was observed, with 60.9% of the patients being male and 39.1% female. This finding aligns with a similar study by Dhooria et al., which reported 59.5% males and 40.5% females among 200 subjects [9]. Furthermore, Yadav et al. demonstrated a male predominance as well, with 54% of their patients identified as male [11]. Similarly, Haridas B et al. noted that 62% of their study participants were male, reinforcing the trend of higher incidence of pancytopenia in males across these studies [8].

The study identified easy fatigability as the most prevalent symptom in patients with pancytopenia, occurring in 85.8% of cases, followed by generalized weakness at 80.4%. Fever was reported in 43.4% of patients, while bleeding manifestations were noted in 33.7%. Yellowish discoloration of the eyes was observed in 39% of the subjects, particularly in those with megaloblastic anemia. A comparative analysis showed that in research by Khan et al., easy fatigability was reported in 90.6% of patients, followed by fever in 37.5% [10]. Haridas B et al. found generalized weakness to be the predominant symptom in about 54% of their subjects, with fever noted in 48% [8]. Overall, consistent findings across studies highlight generalized weakness and easy fatigability as the most common symptoms associated with pancytopenia.

In our study, the most frequently observed clinical sign was pallor, present in 100% of patients. The second most common sign was splenomegaly, noted in 53.2% of cases, followed by icterus at 46.7%. Edema of the feet was seen in 13% of patients, while knuckle pigmentation was present in 44%. Comparatively, a study by Khan et al. found pallor to be the predominant sign in 93.75% of subjects (n=32), with splenomegaly observed in 56.3% and knuckle pigmentation in 21.9% [10]. Further studies by Bhagwan Yadav et al. and Haridas B et al. also reported pallor as the most common sign, with occurrences of 60% and 98% respectively among patients with pancytopenia [8,11].

In a study of 92 pancytopenia patients, 48 were vegetarian and 44 were non-vegetarian. No significant correlation between diet and causes of pancytopenia was found. A similar study by Khan et al. involving 32 patients showed 72% were vegetarian and 28% non-vegetarian [10].

The average hemoglobin in our study was 5.415 g, indicating lower levels compared to a similar study by Dhooria, which reported a mean of 7.16 g. The mean WBC count in our study was 2329.83/mm³, and mean platelet count was 52126/mm³, both of which were similar to Dhooria's findings of 2510/mm³ for WBC and 54885/mm³ for platelets [9].

In our study, the mean MCV for patients with megaloblastic anemia was 95.39 fl, followed by patients with aplastic anemia at 94.2 fl, while the lowest MCV was found in patients with hypersplenism at 74.49 fl. The overall mean MCV was calculated as 85.27 fl, which is higher compared to a similar study by Dhooria et al, which found an MCV of 88 fl [9]. Bone marrow cellularity analysis revealed that 60.8% of samples were hypercellular, 21.7% normal, and 11.96% hypocellular. This aligns with Dhooria's study, where hypercellularity was noted in 42.9% of cases, normal cellularity in 30.3%, and hypocellularity in 26.7%, indicating a predominant finding of hypercellular bone marrow in both studies [9].

The study's peripheral blood analysis showed that 42.39% of smears were dimorphic, 29.35% macrocytic, 16.3% microcytic, and 11.96% normocytic. Comparatively, a study by Dhooria et al reported 34.55% normocytic, 19.5% macrocytic, and 12.5% microcytic patterns, while Goli et al found 45% normocytic, 29.5% macrocytic, and 6% microcytic [9,12]. Thus, this study indicates a predominance of dimorphic blood pictures, unlike the other studies where normocytic patterns were more common.

In a study involving 92 patients, 44 were diagnosed with megaloblastic anemia, consisting of 30 males and 14 females, with a mean age of 37.8 years. All patients exhibited pallor, and the mean hemoglobin level was recorded at 5.19 g%. Additionally, the mean white blood cell (WBC) count was 2469/mm³ and the platelet count averaged 53739/mm³. The average mean corpuscular volume (MCV) for these patients was 95.3 fl. A related study conducted by Haridas B et al. with 50 patients found that 25 had megaloblastic anemia, with a mean hemoglobin level of 4.5 g% [8]. Notably, 72% of patients in the secondary study had platelet counts below 50000/mm³, while 64% had a WBC count ranging from 3000 to 4000/mm³.

In a study involving 92 cases, 10 patients were diagnosed with aplastic anemia, with generalized weakness as the chief complaint. Examination revealed pallor in all patients, with mean hemoglobin levels at 5.3 g% and mean white blood cell (WBC) count at 1960/mm³. Additionally, the mean platelet count was found to be 50,500/mm³. Comparatively, another study by Haridas B et al. involving 50 subjects also identified 10 cases of aplastic anemia [8]. In that study, 100% of the patients exhibited pallor, with 70% having hemoglobin levels below 5 g%, indicating a more severe anemia. Their mean WBC count was notably lower at 1500/mm³. Overall, while mean hemoglobin levels in the current study were slightly higher, the WBC count was significantly lower than that recorded in Haridas B et al.'s study [8].

The study on pancytopenia in a tertiary care hospital included 92 patients, providing a detailed clinical and hematological profile, as well as assessing etiological factors like megaloblastic anemia and dietary influences. However, the single-center design and small sample size limit the generalizability of findings, and observational data restrict causal inference. Recommendations include multicentric studies for broader insights, early nutritional assessments for deficiencies, and prospective studies for evaluating treatment outcomes.

Conclusion

Pancytopenia is a prevalent hematological issue, predominantly affecting patients aged 21 to 30 years, with a male-to-female ratio of 60.8% to 39.2%. Symptoms often include easy fatigability, generalized weakness, fever, and jaundice, while examination signs reveal pallor, splenomegaly, and icterus. A high suspicion for pancytopenia should be maintained in patients presenting with these symptoms, necessitating hematological investigations for early identification and management to improve survival rates.

Declarations

Contributorship

All author contributor equally.

Conflict of Interest

There is no conflict interest.

Funding Statement

None

Acknowledgements

None

Trial details

Not Applicable

Data Availability

All data available on corresponding author upon responsible request.