|Year : 2022 | Volume
| Issue : 3 | Page : 415-421
Clinicopathological features of pancytopenia in adults and the role of bone marrow study in etiological categorization: A one-year cross-sectional study
Abhinab Bhuyan, Prabir Hazarika, Rasadhar Deka
Department of Pathology, Jorhat Medical College, Jorhat, Assam, India
|Date of Submission||05-Apr-2022|
|Date of Acceptance||30-Apr-2022|
|Date of Web Publication||29-Sep-2022|
Department of Pathology, Jorhat Medical College, Jorhat, Assam 781005
Source of Support: None, Conflict of Interest: None
Background and Objectives: Pancytopenia is a combination of anemia (with a reduction of the red blood cell count), leukopenia, and thrombocytopenia. Leukopenia is usually mainly due to a reduction in the neutrophil count although the number of other granulocytes, monocytes, and lymphocytes are often also reduced. Pancytopenia is a manifestation of many serious and life-threatening diseases. This study was undertaken to evaluate the clinicopathological features of pancytopenia and the role of bone marrow study for etiological categorization. Settings and Design: This is a cross-sectional observational study conducted in a tertiary referral center of north east India, for a period of 1 year (from August 2020 to July 2021). Materials and Methods: Proper history taking and clinical examination were done for all patients attending with hemoglobin <10 mg/dL, total leukocyte count <3000 cells/cmm, and platelet count <1 lakh/cmm. The investigations done were peripheral blood smear examination with Leishman stain, special staining, as well as specific biochemical and radiological investigations as per requirement in cases; bone marrow aspiration (under all aseptic precaution); and bone marrow trephine biopsy (under all aseptic precaution). The results are presented in tables and compared with similar studies. Results: A total of 42 cases of pancytopenia were evaluated. The age group of 18–20 years was the most commonly affected. Male-to-female ratio was 1.33:1. All the patients presented with generalized weakness and pallor, and a large portion also with abdominal discomfort, hepatomegaly, and splenomegaly. Anisocytosis and macrocytosis were the most common peripheral blood smear findings. Vitamin B12 level was decreased in 75% of all the evaluated cases (15 of 20 cases). Bone marrow was hypercellular in most of the cases (80.95%) followed by hypocellular marrow (14.29%). Megaloblastic erythroid hyperplasia was the most common abnormality found in bone marrow. Megaloblastic anemia was the most common etiology followed by hypoplastic/aplastic anemia. A significant portion (7.14%) also showed bone marrow involvement by myeloma. One case of involvement by metastatic tumor was found. Conclusions: Most cases of pancytopenia were due to megaloblastic anemia and so easily curable. The bone marrow study is essential to evaluate a case of pancytopenia to know the exact etiology for proper management.
Keywords: Aplastic, hypoplastic, macrocytosis, megaloblastic, pancytopenia
|How to cite this article:|
Bhuyan A, Hazarika P, Deka R. Clinicopathological features of pancytopenia in adults and the role of bone marrow study in etiological categorization: A one-year cross-sectional study. Med J Babylon 2022;19:415-21
|How to cite this URL:|
Bhuyan A, Hazarika P, Deka R. Clinicopathological features of pancytopenia in adults and the role of bone marrow study in etiological categorization: A one-year cross-sectional study. Med J Babylon [serial online] 2022 [cited 2022 Nov 26];19:415-21. Available from: https://www.medjbabylon.org/text.asp?2022/19/3/415/357267
| Key Message:|| |
Although megaloblastic anemia is the most common etiology of pancytopenia, some patients of multiple myeloma also present as pancytopenia.
| Introduction|| |
Pancytopenia is not a disease entity by itself but a triad of clinical findings that result from a reduction of all the three cellular components of blood, namely erythrocytes, leukocytes, and platelets leading to anemia, leukopenia, and thrombocytopenia. Leukopenia is usually due to a reduction in the neutrophil count. Most of the studies in India used following values for the diagnosis of pancytopenia: hemoglobin <10 g/dL, total leukocyte count (TLC) <3500/cmm, and platelet count <1 lakh/cmm.,
The etiology of pancytopenia plays a pivotal role in its management. In Indian scenario, it has been observed that megaloblastosis (vitamin B12 and/or folate deficiency) is the commonest cause of pancytopenia. Other important conditions that manifest as pancytopenia are aplastic/hypoplastic anemia, hypersplenism, storage disease, malaria, myelodysplastic syndrome, multiple myeloma, hairy cell leukemia, and others.,
The aim and objective of the present study is to evaluate the clinicopathological features and etiological spectrum of pancytopenia with the help of bone marrow aspiration and biopsy.
| Materials and Methods|| |
This is a cross-sectional observational study conducted in a tertiary referral center for a period of 1 year (from August 2020 to July 2021). All cases of pancytopenia in adults as evidenced by laboratory investigation in both the sexes were included. Patients undergoing radiotherapy/chemotherapy, uncooperative, unwilling patients, and those who do not give consent were excluded. Patients’ clinical history and examination findings were recorded from the medical record.
Complete blood count was done in Sysmex XN-550 automated hematology analyzer and correlated with manual method when indicated. Peripheral smears were stained with Leishman stain. Vitamin B12 and folic acid estimations were done when necessary. Bone marrow aspiration was done from the posterior superior iliac spine using disposable Salah needle as per the standard operating procedure. Smears were stained with May Grunwald Giemsa stain. Bone marrow biopsy was performed in cases with hypocellular aspiration. Bone marrow biopsy was done with disposable Jamshidi needle (10 and 11G size with a length of 4.5 inches and a bore diameter of 3 mm and 3.5 mm) using the standard operating procedure, fixed in ethelenediamine tetraacetic acid (EDTA), processed in histopathology department and stained with hematoxylin and eosin for examination. Bone marrow smears and biopsy sections were examined by three senior pathologists who were unaware of each other’s observation. Whenever indicated, Pearl’s stain was done in aspirated slides using 0.5% potassium ferrocyanide, 0.75% hydrochloric acid (HCL), and nuclear fast red as counterstain. Bone marrow iron is graded using Gale’s grading system. Reticulin staining was done in a few indicated cases using Gomori’s method. The data collected were presented as tables and charts using Microsoft Word (2010) and Microsoft Excel (2010).
The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki. It was carried out with patients verbal and analytical approval before sample was taken. The study protocol and the subject information and consent form were reviewed and approved by our institutional ethics committee according to the document number 5324(A) dated June 17, 2020.
| Results|| |
A total of 42 patients of pancytopenia were evaluated. The age range was 19–80 years. The most common age group was 18–28 years. Twenty-four patients were male and 18 were female with a male-to-female ratio of 1.33:1.
Symptoms associated with pancytopenia
It is observed that the most common presenting symptom associated with pancytopenia was generalized weakness (42 cases, 100%) followed by abdominal discomfort (16 cases, 38.01% of all), fever with vomiting (seven cases, 16.67%), fever with jaundice (three cases, 7.14%), bleeding manifestation (three cases, 7.14%), fever with rash (two cases, 4.76%), and dyspnea (one case, 2.38%).
Distribution of clinical signs associated with pancytopenia
It is found that the most common clinical sign associated with pancytopenia was pallor (all cases, 100%) followed by hepatomegaly (20 cases, 47.62%), splenomegaly (eight cases, 19.05), edema and enlarged lymph node (four cases each, 9.52% each), and icterus (three cases, 7.14%).
The range of hemoglobin was 3.2–9.8 g/dL, with a mean of 6.06 g/dL and standard deviation (SD) of 1.82 g/dL.
Total leukocyte count
The range of TLC was 900–2945/cmm with a mean of 1824 and SD of 574.
The range of platelet count was 20,000–95,000/cmm. The mean and SD are 48,750/cmm and 27,570/cmm, respectively.
Peripheral blood smear finding
Anisocytosis (38 cases, 90.48%), macrocytosis (21 cases, 50%), and hypersegmented neutrophils (20 cases, 47.62%) [Figure 1] were the most common findings in the peripheral blood smear. A significant number of cases (21 cases, 50%) presented with normocytosis, and a few cases (four cases, 9.52%) presented with dimorphic picture on peripheral blood smear (PBS). No cases of immature cells in PBS were found.
|Figure 1: Bone marrow aspiration showing hypersegmented neutrophils in a case of megaloblastic anemia; oil (1000×), May Grunwald Giemsa stain|
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Bone marrow aspirate and biopsy finding
It is observed that 35 cases (83.33%) showed hypercellular marrow followed by five cases (11.90%) showing hypocellular marrow on bone marrow aspirate study. Also 35 cases (83.90%) showed erythroid hyperplasia, 34 cases (80.95%) showed normal range and the maturation of myeloid series, and 36 cases (85.71%) showed normal megakaryocytic maturation. Five cases (11.90%) showed hypoplasia of all the three lineages [Table 1].
Twenty cases were evaluated for serum vitamin B12, and 15 cases (35.71%) showed a decreased serum vitamin B12 level. There were no cases with ring sideroblasts or increased bone marrow reticulin fibers.
Etiology of pancytopenia
It was found that megaloblastic anemia [Figure 2] was the most common cause of pancytopenia, which was followed by hypoplastic anemia [Figure 3], normoblastic erythroid maturation, and multiple myeloma [Figure 4]. No cases of subleukemic leukemia or aleukemic leukemia were found. One case of metastatic tumor with morphology of malignant small round cell tumor/lymphoma was found [Figure 5] [Table 2].
|Figure 2: Bone marrow aspirate in megaloblastic anemia showing early megaloblasts (horizontal arrow), intermediate megaloblasts (downward arrow), and late megaloblasts (upward arrow); oil immersion (1000×), May Grunwald Giemsa stain|
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|Figure 3: Bone marrow biopsy in aplastic anemia showing markedly hypocellular marrow; low power (100×), H&E stain|
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|Figure 4: Bone marrow aspirate showing involvement by multiple myeloma with many atypical plasma cells; oil immersion (1000x), May Grunwald Giemsa stain|
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|Figure 5: Bone marrow aspirate showing sheets of small round cells suggestive of metastasis of small round cell tumor/lymphoma; high power (400×), May Grunwald Giemsa stain|
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|Table 2: Distribution of final diagnosis associated with pancytopenia with bone marrow study (aspiration and biopsy)|
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| Discussion|| |
Clinical findings (signs and symptoms)
In the study conducted by Shah and Patel (2020), the most common clinical findings were generalized weakness and pallor found in all of the 145 cases (100%) followed by fever (55%), dyspnea (41%), hepatomegaly (14%), and splenomegaly (10%). In the studies conducted by Sharma et al. (2017), Deshpande et al. (2019), Gayathri and Rao (2011), and Suryareshmi et al. (2018), the most common symptoms associated with pancytopenia were generalized weakness complained by all of the 100 patients (100%), 74 of 101 patients (73.2%), all of the 100 patients (100%), and 35 of 46 patients (76.10%), respectively.,,, In the present study, most common clinical symptoms associated with pancytopenia were generalized weakness, which accounted for 100% with all the 42 patients affected by it, followed by abdominal discomfort (38.01%). This shows close resemblance to the study done by Shah and Patel (2020), Sharma et al. (2017), Deshpande et al. (2019), Gayathri and Rao (2011), and Suryareshmi et al. (2018).
In the studies conducted by Yadav and Kumar (2020), Shah and Patel (2020), Pereira and Dias (2016), and Sharma et al. (2017), the most common physical finding observed in the patients of pancytopenia was pallor with 94 out of total 94 cases (100%), 145 out of total 145 cases (100%), 80 out of total 80 cases (100%), and 100 out of 100 cases (100%), respectively, having it.,,, In the present study, the most common clinical sign was pallor with all the 42 (100%) cases showing pallor as physical finding, and so the present study closely resembles to the study conducted by Yadav and Kumar (2020), Shah and Patel (2020), Pereira and Dias (2016), and Sharma et al. (2017).
Peripheral blood findings
In the studies conducted by Agarwal et al. (2018), Gayathri and Rao (2011), and Tilak et al. (1999), the most common PBS finding was anisocytosis found in 94%, 60%, and 83.1% cases, respectively.,, In the present study, anisocytosis was the most common PBS finding found in 90.48% of cases and thus showing resemblance to the studies mentioned above. Agarwal et al.(2018) and Sweta et al. (2014) found macrocytosis as one of the common PBS findings with a prevalence of 45% and 49%, respectively., The present study showed macrocytosis in 50% of cases, which is similar to the above studies.
Bone marrow study
The cellularity of bone marrow was evaluated on the basis of bone marrow aspiration study, and few of the cases were confirmed by a biopsy study with age taken in consideration. In studies conducted by Agarwal et al. (2018), Govindaraj et al. (2015), Varma et al. (2018), Gandhi et al. (2019), and Raina et al. (2020), hypercellularity due to erythroid hyperplasia with megaloblastic changes was the most common bone marrow findings (78.75%, 76%, 56.5%, 67.91%, 81.35%, respectively) followed by hypocellularity (10%, 10%, 10.3%, 14.9%, 15.25%, respectively).,,,, In the present study, the most common finding in bone marrow study was hypercellularity with 35 cases out of total 42 cases (83.33%), followed by hypocellular marrow with five cases out of total 42 cases (11.90%), and thus showing resemblance with the studies performed by Agarwal et al.(2018), Govindaraj et al.(2015), Varma et al. (2018), Gandhi et al. (2019), and Raina et al. (2020).
Etiological diagnosis of pancytopenia
In a study conducted by Shwetha et al. (2021), the most common cause of pancytopenia was megaloblastic anemia (39%) followed by aplastic/hypoplastic anemia (12.17%). In other studies conducted by Mittal et al. (2019), Batool et al., Sweta et al. (2014), Shah et al. (2020), and Gayathri and Rao (2011), the most common causes of pancytopenia, after proper hematological and biochemical evaluation, were megaloblastic anemia (with 33.34%, 27%, 66%, 32%, 77.04% of all cases, respectively) followed by aplastic anemia (with 19.05%, 15.6%, 18%, 16%, 18.26% of all cases, respectively).,,,, In a study conducted by Lakhey et al. (2012), the commonest cause of pancytopenia was hypoplastic anemia (29.6%), followed by hematological malignancies (27.78%). Mangal and Sinha (2020) found aplastic anemia (24.2%) as the most common cause followed by myelodysplastic syndrome (17.6%). Retief and Heyns (1976) concluded bone marrow failure (67.1%) as the commonest cause of pancytopenia followed by hypersplenism (17.7%).
In the present study, the most common cause of pancytopenia was megaloblastic anemia with 26 of total 42 cases (61.90%), followed by aplastic/hypoplastic anemia (11.90%), which is in concordance with studies by Shwetha et al. (2021), Mittal et al. (2019), Batool et al. (2021), Sweta et al. (2014), Shah et al. (2020), and Gayathri and Rao (2011), but in sharp contrast with the studies conducted by Lakhey et al. (2012), Mangal and Sinha (2020), and Retief and Heyns (1976) [Table 3]. Three cases of pancytopenia due to the marrow involvement by multiple myeloma were found in the present study. Bone marrow hypoplasia due to infiltration by multiple myeloma was also found by Medhi et al. One case of metastatic malignancy with features of malignant round cell tumor/lymphoma and one case suspicious of myelodysplastic syndrome were found in the present study. Although these are very significant diagnosis, frequency is not sufficient to compare with other studies or to make a comment. The comparison of common causes of pancytopenia in different literatures and the present study is presented in [Table 3].
|Table 3: Comparison of common causes pancytopenia in different literatures|
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Vitamin B12 assay
In a study by Agarwal et al. (2018), 19 out of 30 cases of megaloblastic anemia were investigated for vitamin B12 assay, and all the cases (100%) showed serum vitamin B12 less than 211 pg/mL (211–946 pg/dL is the normal range in the study). In the present study, 20 of 26 megaloblastic anemia cases were evaluated for serum vitamin B12 level, 15 of which show low level (normal serum vitamin B12 range: 180–640 ng/L). Thus, it can be concluded that the most common cause of megaloblastic anemia in this part of country is nutritional deficiencies, mainly vitamin B12 deficiency, which closely resembles to the study done by Agarwal et al.
| Conclusion|| |
Generalized weakness and pallor were the most common clinical findings associated with pancytopenia followed by abdominal discomfort and hepatomegaly. Megaloblastic anemia was the most common etiology followed by hypoplastic/aplastic anemia. Although bone marrow aspiration is not essential to diagnose megaloblastic anemia, it is necessary to exclude other causes of pancytopenia such as hypoplastic/aplastic anemia, leukemia, plasma cell dyscrasia, metastasis, myelodysplastic syndrome etc. Bone marrow biopsy is essential in hypocellular yield in aspiration to confirm hypoplastic/aplastic anemia and also to confirm space occupying lesions such as metastasis. Plasma cell dyscrasia can present as pancytopenia, which always must be remembered when evaluating a case of unexplained pancytopenia.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]