|Ahead of print publication
A clinico-hematological evaluation of pancytopenia at Government Medical College and Hospital, Latur: A 2-year observational study
Rahul Suryakant Abhange1, Rahul Pundalik Jadhav2
1 Department of Pathology, Government Medical College, Latur, Maharashtra, India
2 Department of Pathology, Government Medical College, Jalgaon, Maharashtra, India
|Date of Submission||12-Dec-2019|
|Date of Decision||26-Jan-2020|
|Date of Acceptance||11-Mar-2020|
Rahul Pundalik Jadhav,
Flat No. 5, Chandrashil Apartment, Behind Kashi Vishweshwar Temple, New Bhagwan Nagar, Jalgaon, Maharashtra
Source of Support: None, Conflict of Interest: None
Context: Pancytopenia is defined by reduction of all the three formed elements of blood below the normal reference. Hematological investigation forms the bedrock in the management of patients with pancytopenia and therefore needs detailed study. The aim of this study was to identify the underlying etiologies of pancytopenia cases presenting at our institute with clinico-hematological evaluation. Materials and Methods: In this 2-year prospective study, 105 patients aged ≥15 years admitted in hospital with a hematological diagnosis of pancytopenia followed by bone marrow aspiration and/or biopsy after receiving an informed consent were studied. The criteria applied for pancytopenia were hemoglobin level: <13.5 g/dL for males and <11.5 g/dL for females; total leukocyte count: <4 × 109/L; and platelet count: <150 × 109/L. Pregnant women and patients aged <15 years along with those who did not give consent for bone marrow aspiration or biopsy were excluded. A detailed clinical examination was carried out in all cases. Results: In the present study, megaloblastic anemia (67.62%) was the most common cause of pancytopenia, followed by aplastic anemia (15.25%), leukemia (3.81%), malaria (3.81%), hypersplenism (3.81%), liver cirrhosis (1.90%), myelofibrosis (1.90%), multiple myeloma (1%), and enteric fever (1%). Conclusions: The severity of pancytopenia and the underlying pathology determine the management and prognosis. Thus, comprehensive clinical and hematological evaluation of pancytopenia cases will help in identification of the correct cause and in implementing the appropriate therapy.
Keywords: Aplastic anemia, bone marrow aspiration, megaloblastic anemia, pancytopenia
|How to cite this URL:|
Abhange RS, Jadhav RP. A clinico-hematological evaluation of pancytopenia at Government Medical College and Hospital, Latur: A 2-year observational study. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2021 Mar 5]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=309185
| Introduction|| |
Pancytopenia is the simultaneous presence of anemia, leukopenia, and thrombocytopenia. It is not a disease entity but a triad of findings that may result from various disease processes, primarily or secondarily involving the bone marrow. Etiology of pancytopenia often varies by geographical region, age, and gender. These include megaloblastic anemia, other nutritional anemia, aplastic anemia (AA), splenomegaly, sepsis, leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes, alcoholic diseases, HIV and hepatitis viruses, autoimmune diseases, endocrine diseases, and bone marrow infiltrating diseases (such as Gaucher disease). The complete hematological workup with good clinical correlation is of utmost importance to evaluate the cause of pancytopenia and planning further investigations.
Although it is a common clinical pattern with an extensive differential diagnosis, there is relatively little discussion of this abnormality in major textbooks of internal medicine and hematology., Underlying pathology determines the management and prognosis of patients. Hence, there is a need to study pancytopenia. This study was carried out:
- To study the underlying etiology of pancytopenia
- To study clinical and hematological profile in cases of pancytopenia.
| Materials and Methods|| |
This study was conducted over 2 years in the department of pathology at our institute. During this study period, a total of 105 cases who presented with pancytopenia and consented for bone marrow examination were selected. Patients aged ≥15 years and both the genders were included. Cases were selected based on the clinical features and supporting hematological evidence of pancytopenia. Clinical details such as age, sex, clinical signs and symptoms, along with hematological parameters, and indications for bone marrow aspiration were recorded in the pro forma. Clinical details with regard to drug intake, weakness, fever, weight loss, organomegaly, lymphadenopathy, bone pain, and gum hypertrophy were also recorded. The peripheral smear was examined along with the reticulocyte count. For bone marrow examination, the procedure was explained to the patient in detail in his/her own language and informed consent was taken. A peripheral smear was made just before performing bone marrow aspiration, and the smears were stained by the Leishman stain for all cases and examined in detail. Bone marrow aspiration was done in a conventional manner. Bone marrow trephine biopsies were performed in cases wherever possible. Final diagnosis was made in each case after clinical and hematological analysis. This study has got clearance from the institutional ethics committee meeting held at Government Medical College, Latur, as per the Ethics Committee Report Reference No.: GMCL/Pharma/IEC/outward No. 193 dated December 2, 2015.
Inclusion criteria were as follows:
- Patients aged 15 years or more admitted at our institute with a hematological diagnosis of pancytopenia followed by bone marrow aspiration or biopsy.
- The criteria applied for pancytopenia were:
- Hemoglobin level: <13.5 g/dL for males and <11.5 g/dL for females
- Total leucocyte count: <4 × 109/L
- Platelet count: <150 × 109/L.
Exclusion criteria were as follows:
- Patients aged <15 years
- Patients who did not give consent for bone marrow aspiration or biopsy
- Pregnant women.
The data compiled were analyzed statistically using percentages, mean, and median for various parameters such as age and sex distribution, presenting symptoms, salient clinical findings, peripheral blood findings, and bone marrow morphology.
| Results|| |
A total of 105 pancytopenia cases were studied. The age of the patients ranged from 15 to 74 years, with a mean (± standard deviation [SD]) of 35.7 (±16.51) years with a male to female (M: F) ratio of 1.33:1. The most common age at presentation was between 15 and 45 years (73.33%), with a slight male preponderance [Table 1]. The most common presentation was generalized weakness seen in 87.62% of the cases, followed by fever, bleeding tendencies, and breathlessness, which constituted 37.14%, 28.57% and 25.71% of cases respectively. 21.90% of cases presented with giddiness, 16.19% of cases with abdominal pain, 15.24% of cases with anorexia and weight loss, and 1.90% of cases presented with bone and joint pain. The most common cause of pancytopenia in our study was megaloblastic anemia (67.62%), followed by AA (15.25%), which was followed by leukemia, malaria, and hypersplenism (3.81% each). Other causes such as liver cirrhosis and myelofibrosis constituted 1.90% cases each, whereas multiple myeloma and enteric fever each constituted 0.95% cases [Table 1].
|Table 1: Sex distribution of pancytopenia across various etiologies in the present study|
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| Discussion|| |
The most common cause of pancytopenia, reported from various studies throughout the world, has been AA, however, in most of the subcontinental studies, megaloblastic anemia was found to be either the most common or the second most common cause of pancytopenia. The variations in the frequency of various diagnostic entities causing pancytopenia in different studies have been attributed to difference in methodology and stringency of diagnostic criteria, geographic area, period of observation, genetic differences, and varying exposure to myelotoxic agents.
In the present study, the age of the patients ranged from 15 to 74 years with a mean (±SD) of 35.7 (±16.51) years with M: F ratio of 1.33:1. The most common age at presentation was between 15 and 45 years (73.33% cases), with a slight male preponderance. In a similar study, Gayathri and Rao observed pancytopenia in the age group of 2–80 years with a mean age of 41 years and M: F ratio of 1.2:1. Jha et al. observed pancytopenia in the age group of 1–79 years, with a mean age of 30 years and M: F ratio of 1.5:1.
The most common presentation was generalized weakness seen in 87.62% of the cases, followed by fever, bleeding tendencies, and breathlessness which constituted 37.14%, 28.57%, and 25.71% cases, respectively. In a study by Khodke et al., fever (40%) was the most common symptom followed by weakness (30%) and bleeding manifestation (20%). In another study by Ghartimagar et al., weakness (86.95%) was the most common symptom, followed by dyspnea (42.30%), fever (32.60%), and bleeding manifestations (13.04%).
The most common cause of pancytopenia in this study was megaloblastic anemia seen in 67.62% cases, similar to the study by Tonape and Shende (65.71%) and by Javalgi and Dombale (73.5%)., In other similar studies, its frequency ranged from as low as 13.04% to as high as 68%. In the present study, the age ranged from 15 to 74 years among cases of megaloblastic anemia. Mean (± SD) age for megaloblastic anemia was 34.68 years (±15.44). There was male preponderance and the M:F ratio was 1.45:1. Similar results were obtained in a study by Gayathri and Rao. Bone marrow aspirate from all (100%) the cases of megaloblastic anemia showed erythroid hyperplasia with megaloblastic maturation [Figure 1]. Features of dyserythropoiesis also noted in an aspirate from 35.21% of cases. Myelopoiesis showed giant metamyelocytes and giant band forms [Figure 2]. In a study by Chandra and Kumar, bone marrows in cases of megaloblastic anemia were hypercellular (100%) with characteristic megaloblastic erythropoiesis overrepresented by early erythroid cells in comparison with mature forms due to ineffective erythropoiesis. Features of dysmyelopoiesis were evident in the form of giant metamyelocytes and band forms. Megakaryocytes were hyperlobated. In a study by Gandhi et al., bone marrow aspirates were hypercellular (67.91%) and showed megaloblastosis. Majority of the studies which have been done in India stress the importance of megaloblastic anemia being the major cause of pancytopenia. As facilities for estimating folic acid and Vitamin B12 levels are not routinely available in most centers in India, which was also the case in the present study, the exact deficiency is usually not identified. People in India and other developing nations continue to suffer from vitamin deficiencies, which cause anemia and pancytopenia. These are easily preventable if diagnosed and treated early.
|Figure 1: Bone marrow aspiration smear showing erythroid hyperplasia with megaloblastic maturation – Megaloblastic anemia (Leishman, ×40)|
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|Figure 2: Bone marrow aspiration smear showing megaloblastic maturation with royal blue cytoplasm and sieve-like chromatin along with giant metamyelocyte and band form – Megaloblastic anemia (Leishman, ×100)|
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The second most common cause of pancytopenia in the present study was AA seen in 15.25% which correlated with the study done by Khodke et al., whose incidence for the same was 14%. A higher incidence of 29.5% was reported in a study by Dubey et al. AA most commonly presents in children and young adults, but there is second smaller peak in the incidence after age 60 years. In the present study, age (mean) ranged from 15 to 74 years (38.25 years) with male preponderance showing M: F ratio of 1.66:1 among cases of AA. Similar results were seen in the studies by Dubey et al. and Jha et al. In the present study, bone marrow was hypocellular and the aspirate was mostly composed of fat cells in all (100%) patients with AA [Figure 3]. There was relative increase in plasma cells and lymphocytes. Bone marrow trephine biopsy revealed replacement of marrow by fat cells [Figure 4]. Similar results were observed in the study by Gandhi et al. where bone marrow was hypocellular in 100% of AA cases.
|Figure 3: Bone marrow aspiration smear showing markedly hypocellular bone marrow containing fat fragments – Aplastic anemia (Leishman, ×10)|
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|Figure 4: Bone marrow biopsy showing hypocellular marrow spaces with few hematopoietic cells in between – Aplastic anemia (H and E, ×10)|
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Acute leukemia accounted for 3.81% of total pancytopenia cases which correlated with the study by Gayathri and Rao, which constituted 3.85% cases of pancytopenia caused by acute leukemias. Among acute leukemia cases in the present study, 50% were constituted by acute myeloid leukemia and 50% by acute lymphoblastic leukemia. The bone marrow was hypercellular showing myeloid hyperplasia with predominantly immature cells (blasts) [Figure 5] along with reduced erythropoiesis and megakaryopoiesis in all (100%) cases. Patel et al. reported bone marrow to be hypercellular in all (100%) cases of leukemia presenting with pancytopenia. Gandhi et al. in their study found bone marrow to be hypercellular in 85.18% of cases.
|Figure 5: Bone marrow aspiration smear showing markedly increased promyelocytes with convoluted nuclei and containing abundant reddish-purple cytoplasmic granules and Auer rods More Details. Other series cells are markedly suppressed – Acute myelogenous leukemia-M3 (hypergranular type) (Leishman, ×100)|
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Malaria was the cause of pancytopenia in 3.81% of the cases in the present study. Peripheral smears showed anisopoikilocytosis along with ring forms and schizonts of Plasmodium vivax and gametocyte of Plasmodium falciparum. In a study by Patel et al., malaria was the cause of pancytopenia in 4% of cases.
Hypersplenism is known to cause pancytopenia by the sequestration of blood cells. Hypersplenism was the cause of pancytopenia in 3.81% of cases. Bone marrow was hypercellular in all the cases. Dubey et al. reported an incidence of hypersplenism in 15.7% cases of pancytopenia in their study.
Other causes were liver cirrhosis and myelofibrosis, accounting for 1.90% of the cases each followed by multiple myeloma and enteric fever accounting for 0.95% of cases of each. Patel et al. reported cirrhosis of liver as a cause of pancytopenia in 8% of cases. Manzoor et al. found myelofibrosis as a cause of pancytopenia in 2% of cases in their study. Javalgi and Dombale, in their study, reported pancytopenia due to multiple myeloma in 0.9% of cases. Dubey et al. reported enteric fever as a cause of pancytopenia in 1.2% of cases.
[Table 2] shows the distribution of most common causes of pancytopenia in various studies.
The study had a small sample size and it was done at a single center in the region. Larger sample size and sampling from multiple centers in the region would have provided much clearer picture of the situation. Further, the facilities for estimating folic acid and Vitamin B12 levels were not available at our institute; hence, the exact deficiency could not be identified in megaloblastic anemia cases.
| Conclusions|| |
The varied causes of pancytopenia can be attributed to the geographic area, genetic differences, stringency of diagnostic criteria, and differences in methodology used. There are varying trends in its clinical pattern, treatment modalities, and outcomes. The severity of pancytopenia and the underlying pathology determine the management and prognosis. Thus, identification of the correct cause will help in implementing the appropriate therapy. Clinical assessment followed by a complete hemogram and bone marrow examination is a very essential step in planning further management and prognosis of pancytopenia patients.
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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]