|Year : 2020 | Volume
| Issue : 2 | Page : 232-237
Evaluation of cytopenias in pediatric patients for etiology
Bidisha De1, Shweta Bahadure1, Arvind Bhake2
1 Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha, Maharashtra, India
2 Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha, Maharashtra, India
|Date of Submission||16-Apr-2020|
|Date of Decision||20-Apr-2020|
|Date of Acceptance||30-Apr-2020|
|Date of Web Publication||21-Dec-2020|
Dr. Shweta Bahadure
DMIMS, Sawangi (M), Wardha, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Pancytopenia is a common occurrence in paediatric patients. Aetiology of bicytopenia/ pancytopenia varies widely children, ranging from transient marrow suppression to marrow infiltration by life threatening malignancies. In time recognition of the underlying pathology will not only have an impact on mortality and morbidity but also help in treating simple and easily treatable conditions causing pancytopenia. Aim: To evaluate the etiological and clinicohaematological profile in children with cytopenias. Objectives: To study the clinical presentations in patients with pancytopenia/bicytopenia and evaluate hematological parameters and the bone marrow aspirates. Materials and Method: The present work was carried out in the hematology section of Department of Pathology, of a central Indian medical college and rural hospital from December 2017 to December 2018. 100 patients in paediatric age group having pancytopenia/bicytopenia on peripheral smear were included in the study. All relevant investigations were carried out including Bone marrow aspiration. A correlation between bicytopenia/ pancytopenia with symptoms and etiology was made. Result: The main presenting features of children with both pancytopenia and bicytopenia was fever and the commonest non-malignant conditions causing bicytopenia was megaloblastic anaemia and aplastic anaemia in pancytopenia and the commonest malignant condition which was associated with bicytopenia and pancytopenia was acute leukaemia. Conclusion: Primary haematological investigations along with bone marrow aspiration in cytopenic patients which will be helpful for understanding the disease process; diagnosis, or will help to rule out the causes of, cytopenia; and in planning further investigations and management of cytopenic patients.
Keywords: Acute leukemia, aplastic anemia, bicytopenia, megaloblastic anemia, pancytopenia
|How to cite this article:|
De B, Bahadure S, Bhake A. Evaluation of cytopenias in pediatric patients for etiology. J Datta Meghe Inst Med Sci Univ 2020;15:232-7
| Introduction|| |
Cytopenia is when the production of one or more blood cell types (red blood cells, white blood cells, or platelets) ceases or is greatly reduced. Bicytopenia is the reduction in any of the two cell lines. Pancytopenia is the simultaneous presence of anemia, leukopenia, and thrombocytopenia. It exists when hemoglobin is <10 g/dl; leukocyte count is <4 × 103/L; and the platelet count is <150 × 103/L.
Pancytopenia is a common occurrence in pediatric patients. There are various hematopoietic and nonhematopoietic conditions which manifest with features of pancytopenia. The underlying mechanisms are decreased in hematopoietic cell production, marrow replacement by abnormal cells, suppression of marrow growth and differentiation, ineffective hematopoiesis, defective cell formation which are removed from the circulation, antibody-mediated sequestrum, or destruction of cells and trapping of cells in hypertrophied and over active reticuloendothelial system.
Etiology of bicytopenia/pancytopenia varies widely children, ranging from transient marrow suppression to marrow infiltration by life-threatening malignancies. Pancytopenia can occur as a consequence of autoimmunity and immune dysregulation. Evans syndrome is often a manifestation of autoimmune lymphoproliferative syndrome. Cytopenias can occur in acquired, multifactorial autoimmune syndromes such as systemic lupus erythromatosis or primary antiphospholipid syndromes. Other primary immunodeficiencies leading to autoimmune cytopenias are leaky severe combined immunodeficiency, WAS, hyper-IgM syndrome, and common variable immunodeficiency syndromes. Immune dysregulation is also the cause of pancytopenia in patients with hemophagocytic lymphohistiocytosis.,
Certain extrinsic, environmental conditions can interfere significantly with blood formation, either prenatally or postnatally. The most frequent causes of impaired hematopoiesis are infections, congenital TORCH infections (i.e., toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and others). Many other viral infections are associated with transient hematopoietic depression of one or more lineages. Important infections to be considered in differential diagnosis of peripheral cytopenias are hepatitis C, human immunodeficiency virus (HIV), Helicobacter pylori, and leishmaniasis.,
Overlapping phenotypes and pathophysiologies pose a major diagnostic challenge. However, an accurate and rapid diagnosis is essential for adequate therapy, planning, and surveillance. It is imperative to perform detailed clinical examination, history taking, and complete hematological work-up to evaluate the causes of pancytopenia/bicytopenia in pediatric subjects as well as to understand the significant differences in their etiology and manifestation. Careful examination of peripheral smear for cellular morphology is important. Reticulocyte count should be done to assess erythropoietic activity. Bone marrow examination plays an important role in understanding the etiology of pancytopenia. Bone marrow examination should include bone marrow aspiration along with biopsy wherever indicated.
In time recognition of the underlying pathology will not only have an impact on mortality and morbidity but also help in treating simple and easily treatable conditions causing pancytopenia.
Studies related to pancytopenia/bicytopenia in the pediatric age group are scarce in literature. The present study is being undertaken with the aim to determine etiological, clinical, and hematological correction in pediatric patients with bicytopenia/pancytopenia.
Other causes of suppressed hematopoiesis are nutritional deficiency such as Vitamin B12, folate, and iron deficiency.
Various inborn genetic defects on hematopoietic failure are Fanconi's anemia, dyskeratosis congenita, congenital amegakaryocytic, thrombocytopenia, thrombocytopenia with absent radii, diamond Blackfan anemia, and Shwachman diamond syndrome have been subsumed as inherited bone marrow failure syndromes.,
Nonmalignant cause of acquired pancytopenia is aplastic anemia followed by megaloblastic anemia (MA). These may also be caused iatrogenetically, secondary to certain drugs, chemotherapy or radiotherapy for malignancies.,
Among the malignant causes, acute leukemia is the most common cause. Acute lymphoblastic leukemia being a more common.
Pancytopenia per se is not a disease but a feature of various diseases causing impact on bone marrow and eventually resulting in this condition. There is variability in its clinical presentation, treatment options, and prognosis. The main presenting features in children with pancytopenia are fever and pallor. Other common symptoms are petechial rash, bleeding, and bone pain. Dyspnea on exertion, easy bruising, epistaxis, gingival bleeding, and headache may be presenting features. On clinical examination, hepatomegaly and splenomegaly may be found.,
This study aims to evaluate the etiological and clinicohematological profile in children with cytopenias.
- To study the clinical presentations in patients with pancytopenia/bicytopenia
- To evaluate hematological parameters
- To evaluate bone marrow aspiration smear in patients with pancytopenia/bicytopenia
- To study the etiological profile in patients with cytopenias.
| Materials and Methods|| |
The present titled “Evaluation of cytopenias in pediatrics patients for etiology” was carried out in Department of Pathology, J. N. M. C., Sawangi (Meghe), Wardha with the aim to evaluate etiological and clinicohematological profile in children with bicytopenia/pancytopenia.
Sample size - 100 patients in pediatrics age group visited AVBRH and had pancytopenia/bicytopenia on peripheral smear.
Study design – prospective study, observational mid-term.
Study duration – from December 2016 to December 2018
Inclusion criteria – the inclusion criteria will be patients aged 1 month to 14 years, who has pancytopenia on peripheral blood smear, and guardians who will give consent for admission and bone marrow examination.
- Exclusion criteria – patients more than 14 years of age
- Diagnosed cases of aplastic anemia and leukemia, clinical suspicion of genetic, or constitutional pancytopenia
- History of blood transfusion in the recent past
- Those who are not willing for admission or for bone marrow examination.
Source of data – peripheral smear of pediatrics patients suspicious of having pancytopenia/bicytopenia was received from the Department of Pediatrics, AVBRH.
Materials – after obtaining clearance from IEC and written informed consent from parents/guardians detailed history was taken including dietary intake, ingestion of any drugs, worm infestation and loss of blood and duration of onset of anemia.
All relevant investigations were done including complete blood count (CBC) along with peripheral smear examination to check out cellular morphology. Red cell indices, Vitamin B12 levels, liver profile, HIV 1 and 2, bleeding profile.
Two milliliter of ethylenediaminetetraacetic acid anticoagulated blood was collected and processed in automated hematological analyzer. Blood count was done on coulter and was confirmed by peripheral smear examination. Peripheral smear was stained with Leishman stain. Cytopenia is defined as hemoglobin <10 g/dl, total leukocyte count (TLC) <4 × 109/L, and platelet count <100 × 109/L.
Bone marrow aspiration was carried out as per clinical indication. Bone marrow aspiration was performed from posterior superior iliac spine under aseptic conditions. All the bone marrow aspirate smears were stained with May-GG star and examined. Other special stains such as myeloperoxidase, periodic acid–Schiff, and Perls Prussian Blue were performed wherever necessary.
Bone marrow biopsy was done in cases where bone marrow aspiration was inconclusive. All the investigations to reach the diagnosis were recorded. Only those cases in which diagnosis could be confirmed were included for final analysis.
The statistical analysis was carried out using Chi-square test. P < 0.01 was considered statistically significant.
Ethical approval for this study (DMIMS(DU)/IEC/2018-19/845) was provided by the Ethical Committee of Datta Meghe Institute of Medical Sciences (Deemed to be University) on 15/1/2018.
| Results|| |
The present study was carried out in the Department of Pathology, JNMC Sawangi Meghe, Wardha during 2017–2019.
A total of 115 cases presented with the clinical diagnosis of pancytopenia or bicytopenia, out of which 100 cases were screened for the study. Fifteen cases were excluded as they were of the exclusion criteria. After carrying out all relevant investigations on 100 cases, they were labeled into two groups depending on the presence of either bicytopenia or pancytopenia.
Of 68 patients of pancytopenia, 40 (58.82%) males and 28 (41.17%) were females, their ages ranged from 1 month to 14 years. Maximum number of patients 28 (41.17%) were in the age group of 6 years to 10 years. All age groups had male predominance.
Of 32 patients of bicytopenia, 14 (43.75%) were male and 18 (56.25%) were female. Maximum number of patients 18 (56.25%) were in the age group of 11–14 years. 6–14 years of age group shows females predominance.
Hematologically, thrombocytopenia, and anemia were the most common cause of bicytopenia in 25 cases, followed by anemia and leukocytopenia in 6 cases and in 1 case.
Peripheral smear findings
- Almost all cases show anisopoikilocytosis
- Hypersegmented neutrophils are seen in almost all cases of MA
- Blasts are seen in peripheral smear in almost all cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
The main presenting features of children with bicytopenia were fever (65.62%) and pallor (50%). The most common physical finding was hepatomegaly (75%) and splenomegaly (31.25%).
The main presenting features of children with pancytopenia were fever (92.64%) and pallor (76.47%). On clinical examination, hepatomegaly was seen in (51.47%) and splenomegaly was seen in (41.17%) cases.
[Table 6] shows the most common nonmalignant conditions causing bicytopenia were MA followed by aplastic anemia, malaria, marrow granuloma, immune thrombocytopenic purpura, storage disorders. The most common malignant condition which was associated with bicytopenia was acute leukemia. Of the acute leukemia, 3 cases were of ALL and 1 case was of AML.
The most common nonmalignant condition causing pancytopenia was aplastic anemia followed by MA. Malignancy leading to pancytopenia was acute leukemia, Of the acute leukemias, 12 cases were of ALL and 5 cases of AML of which 1 was AML-M1, 2 were AML-M2, 1 was AML-M3, and 1 was AML-M5.
In nonspecific group, there were 5 children, of these 2 children had bicytopenia and 3 had pancytopenia. Bone examination in these children showed normocellular marrow in 4 and was hypercellular in 1. Of these, 4 children showed no specific changes in bone marrow and 1 showed erythroid hyperplasia.
Bone marrow aspirate examination
Bone marrow aspiration was carried out in 23 cases where the result was inconclusive on peripheral smear. Of 20 patients with pancytopenia diagnosed with bone marrow aspiration, 8 cases had aplastic anemia followed by 5 cases of MA and 4 cases of acute leukemia mainly ALL. Three cases had suspicious hematomorphological bone marrow aspiration finding and therefore was subjected to bone marrow biopsy for confirmation. Three cases had confirmatory diagnosis of bicytopenia on bone marrow aspiration. All the cases of bicytopenia were diagnosed with ALL [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6].
|Table 1: Distribution of cases in two groups pancytopenia or bicytopenia|
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|Table 2: Distribution of cases of pancytopenia according to age and gender|
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|Table 3: Distribution of cases of bicytopenia according to age and gender|
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|Table 4: Hematological profile in children with pancytopenia and bicytopenia|
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|Table 5: Frequency of symptoms and signs in children with bicytopenia and pancytopenia|
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|Table 6: Etiological profile of children with bicytopenia and pancytopenia|
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| Discussion|| |
Pancytopenia is a triad of findings that results from various disease processes affecting the marrow primarily or secondarily. The diagnosis of pancytopenia requires microscopic examination of peripheral smear and bone marrow aspirate.
Pancytopenia/bicytopenia can be caused due to ineffective erythropoiesis, increased peripheral destruction of cells or decreased production of hematopoietic cells in bone marrow.
CBC is usually the initial investigation that reveals pancytopenia/bicytopenia. Determining the exact etiology is of prime most importance for specific treatment and prognosis. Bone marrow aspirate and bone marrow biopsy becomes indispensable investigations.
The present study was conducted on 100 cases of either pancytopenia or bicytopenia.
In our study, the cases were categorized into two groups, i.e., bicytopenia and pancytopenia. It was observed that 32% of cases were in the category of bicytopenia and 68% of cases were in the category of pancytopenia which was unlike the study conducted by Sharif et al.
In our study, the patients were from 1 month to 14 years of age. Maximum number of cases with pancytopenia belonged in the age group between 6 and 10 years. 41.7% cases followed by 33.82% cases in the age group between 11 and 14 years. Whereas maximum cases (58.25%) with bicytopenia, belonged to 11–14 years of age group followed by 28.1% cases in 6–10 years of age group and the least number of cases 15.56% were in 0–5 years' age group. This finding was similar to the study conducted by Singh et al. whereas Shams et al. found that the most common age group with pancytopenia/bicytopenia was between 12 and 16 years. Savage DG. had the maximum number of cases with pancytopenia in 6 months to 5 years of age unlike the finding in our study.
In our study, 58.82% of cases with pancytopenia were male and 41.17% of cases were females. Similarly, in cases with bicytopenia 56.25% of cases were females and 43.75% cases were males.
It was found that maximum number of cases with pancytopenia/bicytopenia were males which was in concordance with studies conducted by Sharif et al., Shams et al., Naseem et al., Singh et al., Anwar Zeb et al., Bhatnagar et al. Whereas study conducted by Tufail et al., Krishna Dubey et al. found a female preponderance.
In our study, hematological profile namely hemoglobin, total leucocyte count, platelet count was studied in both bicytopenic and pancytopenic patients. It was observed that all the cases with bicytopenia/pancytopenia had hemoglobin <10 g/dL. 25% of the cases with bicytopenia had TLC <4000 cells/cumm and the rest 75% cases had platelet <1 lakh/cumm along with Hb <10 g/dL. The pancytopenic patients had platelets <1 lakh/cumm and TLC <4000/cumm and Hb <10 g/dL.
It is inferred that all the cases with pancytopenia had decreased Hb, platelet count, and TLC where as in bicytopenic cases along with decreased Hb, the platelet count was found to be on the lower side in most of the cases. The finding was similar to the studies by Singh et al. and Naseem et al.
In our study, the frequency of signs and symptoms was studied in children with bicytopenia/pancytopenia. Fever was the most common symptom in both pancytopenic (92.64%) and bicytopenic (65.62%), followed by pallor.
The most common physical finding in bicytopenic (34.37%) and pancytopenic (41.17%) was hepatomegaly followed by splenomegaly and lymphadenopathy. This finding was akin to the studies conducted by Singh et al., and Naseem et al.
In our study, the etiology of pancytopenia and bicytopenia was categorized under malignant and nonmalignant categories as follows. Most of the etiological profiles of bicytopenia was nonmalignant. In bicytopenic patients, the most common cause under nonmalignant conditions was aplastic anemia followed by MA. Where was under malignant category, the most common etiological factor was found to be acute leukemia mainly ALL. This finding was in concordance with the study by Naseem et al., Shams et al., and Singh et al.
Most of the etiological conditions of pancytopenia was nonmalignant. In pancytopenic patients, the most common cause under nonmalignant category was aplastic anemia (25 cases) followed by MA (15 cases). Moreover, under malignant categories, the most common etiological cause was acute leukemia (17 cases) mainly ALL. Those findings were in concordance with the studies by Naseem et al. and Shams et al. which was unlike the findings by Singh et al. where MA was the most common cause etiology for pancytopenic patients.
The most common cause of pancytopenia on bone marrow aspiration was followed to be aplastic anemia (8 cases) followed by MA (5 cases). All the cases of bicytopenia were diagnosed with ALL.
A study conducted by Lakhey et al. had hypoplastic bone marrow as the most common finding of bone marrow aspiration in pancytopenic cases followed by hematologic malignancies and MA whereas study conducted by Shams et al. found the most common diagnosis on bone marrow aspiration was aplastic anemia followed by MA and acute leukemia. The result was in concordance with our study. Krishna Dubey et al. found MA as the most common etiology in bone marrow aspiration unlike the finding in our study.
| Conclusion|| |
Pancytopenia is not an uncommon hematological problem encountered in clinical practice and should be suspected on clinical grounds when a patient presents with unexplained anemia, prolonged fever and tendency to bleed. In our study, we have included primary hematological investigations along with bone marrow aspiration in cytopenic patients which will be helpful for understanding the disease process; diagnosis, or will help to rule out the causes of, cytopenia; and in planning further investigations and management of cytopenic patients. Severe pancytopenia has significant relation with the clinical outcome and can be used as a prognostic indicator.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]