|Year : 2014 | Volume
| Issue : 2 | Page : 45-50
A prospective clinico-hematological study in 100 cases of pancytopenia in capital city of India
Sweta1, Sumit Barik2, Raj K Chandoke2, Anand K Verma2
1 Department of Transfusion Medicine, ESI PGIMSR, New Delhi, India
2 Department of Hematology and Pathology, ESI PGIMSR, New Delhi, India
|Date of Web Publication||19-Jul-2014|
C-1008, Supertech Apartment, Indirapurm, Ghaziabad, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Context: Pancytopenia is not a disease but a clinico-hematological entity encountered in clinical practice. A prompt intervention is required to avoid complications, which can occur in these patients. The relevant clinical history and complete hematological workup is required to treat patient of pancytopenia. The severity of pancytopenia and the underlying pathology determines the management and prognosis. Aims: To diagnose different conditions producing pancytopenia on the basis of clinical, hematological and bone marrow studies. To estimate the frequency of different diseases producing pancytopenia. Subjects and Methods: The study was conducted in Department of Hematology of our college in capital city of India. A prospective study was carried out among 100 consecutive patients with pancytopenia. Blood samples of the patients were analyzed for red cells, white cells and platelets morphology along with presence and absence of immature cells and abnormal cells. In bone marrow examination, morphology of all cells lineage, cellularity, parasite and abnormal cells were scrutinized. Trephine biopsy was done where ever indicated. Results: The age of patients ranged from 5 to 80 years. 74% of patients in this study were vegetarian. The most common cause of pancytopenia was megaloblastic anemia (66%) followed by aplastic anemia (18%), malaria (6%), kala-azar (4%), acute myeloid leukemia (2%), multiple myeloma (2%), myelodysplastic syndrome (1%), and tuberculosis (1%). Conclusions: The present study concludes that detailed primary hematological investigations along with bone marrow examination in cytopenic patients is helpful for understanding disease process, to diagnose or to rule out the causes of pancytopenia. It is also useful in planning further investigations and management.
Keywords: Aplastic anemia, kala-azar, malaria, megaloblastic anemia, pancytopenia
|How to cite this article:|
Sweta, Barik S, Chandoke RK, Verma AK. A prospective clinico-hematological study in 100 cases of pancytopenia in capital city of India. J Appl Hematol 2014;5:45-50
|How to cite this URL:|
Sweta, Barik S, Chandoke RK, Verma AK. A prospective clinico-hematological study in 100 cases of pancytopenia in capital city of India. J Appl Hematol [serial online] 2014 [cited 2018 Jan 22];5:45-50. Available from: http://www.jahjournal.org/text.asp?2014/5/2/45/137139
| Introduction|| |
Pancytopenia is simultaneous presence of anemia, leukopenia and thrombocytopenia. , It is generally due to decrease in hematopoietic cell production in the marrow resulting from infections, toxins, malignant cell infiltration, chemotherapies and radiation.  Different studies done at different places showed variable frequency of pancytopenia. ,, Identification of the disease is of prime importance, since this is the key to appropriate management. 
Patient with pancytopenia presents with different clinical features. Marrow cellularity and composition in cases of pancytopenia differ in relationship to underlying pathological condition. The marrow is generally hypocellular in cases of pancytopenia caused by a primary production defect. Cytopenias resulting from ineffective hematopoiesis, increased peripheral utilization or destruction of cells, and bone marrow invasive processes are usually associated with a normocellular or hypercellular marrow.  This study was carried out with the aim to obtain detailed clinical and hematological spectrum of the common disorders producing pancytopenia in patients attending our hospital, its causes and diagnostic approaches and thereby automatically enhance the management process.
| Subjects and methods|| |
This study was approved by the Local Ethical Committee to be conducted in our hospital. This was a prospective study that included patients with pancytopenia who were registered in our hospital and hemogram was sent in Department of Hematology. A total number of 100 patients, who were referred with the diagnosis of pancytopenia, were included in the study.
Inclusion Criteria for this Study Were
Patients with hemoglobin: <10 g/dl, total leukocyte count: <4300/cu.mm, platelet count: <130,000/cu.mm.
Exclusion Criteria for this Study Were
Diagnosed cases of malignancy, including leukemia receiving chemotherapy or radiotherapy. Patients were selected according to the guidelines of inclusion criteria. All the patients were subjected to examination of their complete blood count and peripheral blood smear examination. Bone marrow aspiration and/or bone marrow biopsy was done in cases where required. Marrow were examined for cellularity, myeloid: Erythroid ratio, erythropoiesis, myelopoiesis, megakaryopoiesis, other cells such as plasma cells, lymphocytes, blasts and parasites. Special investigations were done in cases where indicated. Patients were followed until discharge and response to therapy was noted.
| Results|| |
During the study, 59,856 blood samples were received for complete blood counts in the laboratory. Of these 100 successive patients who met the inclusion criteria were selected and subjected for the study to find out cause of pancytopenia. The clinical and hematological examination, including bone marrow examination were done.
Following results were recorded and analyzed.
Analysis of Clinical Features
The minimum age was found to be 5 years and maximum age was 80 years. No patient below 5 years of age was found in these 100 consecutive patients with pancytopenia. The maximum number of patients were between the age group of 21 and 35 years 43% followed by 5 and 20 years 22%. Nineteen percentage of cases were between 36 and 50 years. Eleven percentage of the cases were between 51 and 65 years. About 5% of the cases were more than 65 years.
The incidence of pancytopenia showed preponderance among males. The male to female ratio was 1.56:1. Of the total 66 cases of megaloblastic anemia, 42 (63.6%) were males and 33.4% (24) were females, likewise in aplastic anemia, among the total 18 cases, 11 (61.2%) were females and 7 (38.9%) were males. Out of the 6 cases of malaria, 4 (66%) were males and 2 (33%) were females, in kala-azar among the 4 cases, 3 (75%) were male 1 (25%) was female, in acute myeloid leukemia (AML) both the cases 2 (100%) were male, in multiple myeloma also both the cases were male 2 (100%). Similarly, the one case of myelodysplastis syndrome (MDS) was female 1 (100%), and one case of tuberculosis was male 1 (100%) [Table 1].
Analysis of Hematological Investigations
The hemoglobin concentration was between 8 and 10 g/dl in 24% of cases. In 24% of the cases it was between 6 and 8 g/dl. Fifty-two percentage of the cases had hemoglobin <6 g/dl, which formed the major group of patients who had pancytopenia.
The total leukocyte count was between 3300 and 4300/cu.mm in 40% of cases. In 39% of the cases, the leukocytes count was between 2300 and 3300/cu.mm. In 21% of the cases it was <2300/cu.mm.
The platelet count was between 100,000 and 130,000/cu.mm in 19% of the cases. In 42% of cases it was between 70,000 and 100,000/cu.mm, and in 39% of cases it was <70,000/cu.mm.
The mean corpuscular volume (MCV) was increased in 49% of the total cases of pancytopenia, and megaloblastic anemia was the cause. It was decreased in 7% of cases and was found to be within the normal range in 44% of the cases. The reticulocyte count was within normal range in 70% of the cases. Twenty percentage of the cases showed a decreased reticulocyte count. An increased count was seen in 10% of cases and these were those cases with malaria and kala-azar, which represent a relative increase in pool of immature red blood cells (RBCs). The predominant blood picture was macrocytic anemia constituting 49%, followed by normocytic anemia seen in 42% of the cases. Dimorphic picture was seen in 9% of cases. Circulating megaloblasts were found in 16 (16%) patient with pancytopenia. Giant platelets were seen in 14 (14%) patients with pancytopenia. Hypersegmented neutrophils were seen in 47 (47%) cases. Relative lymphocytosis was seen in 16 (16%) patients. Malarial parasites were seen in 6 (6%) of the total cases.
Bone marrow examination was required in 94 cases only. Six cases of malaria were diagnosed on the basis of peripheral blood examination. Bone marrow was hypercellular in 72 cases, which included 66 cases of megaloblastic anemia. Cellularity was decreased in 19 cases, including 18 cases of aplastic anemia and one of miliary tuberculosis (miliary TB). Normal marrow cellularity was seen in three cases. Megaloblastic maturation, presence of blasts, abnormal plasma cells and presence of leishman donavan (L.D.) bodies were diagnostic features in bone marrow examination. Myelodysplasia was seen in one case and showed dysplastic features in all the three lineages, however ring sideroblasts were absent. 80 patients responded to therapy and followed-up until there was substantial improvement. 19 cases were referred to advanced hematology centers for further treatment. Only one case died during the study period, which was pancytopenia with miliary TB.
| Discussion|| |
This study was conducted in postgraduate institute of metropolitan capital city of India.
The institute provides specialty and superspecialty services to the patients covered under social security and insurance scheme known as Employee State Insurance run by Government of India.
During the study, 59,856 blood samples were received for complete blood counts in the laboratory. Of these, 100 successive patients who met the inclusion criteria were selected. Pancytopenia was the most common indication for bone marrow examination in our hospital during this period and comprised as much as 42% of the cases, in which bone marrow was examined. This is high compared with that in the studies of Tilak and Jain  and Khodke et al.  in which they were 37.6% and 20%, respectively. Similarly, Jha et al.  has mentioned it be 15.74% of the total of bone marrow examinations.
In this study of pancytopenia patients, the highest incidence of 43% was in the age group of 21-35 followed by 22% in 5-20 age group, with a mean age of 42 years. Similarly, Khodke et al.  found the maximum number of pancytopenia in the age group of 12-30 years. About 10% of the cases were above 50 years. Jha et al.  and Ishtiaq et al.  in their studies found mean ages to be 30 years and 36.7 years, respectively. Niazi and Raziq  in their study found most common age group of pancytopenia in the range from 21 to 30 years.
Of 100 cases, 61% were males and 39% were females with the male to female ratio of 1.56:1. The male to female ratio in this study is same as in the study by Jha et al.  The ratio was 1.3:1 in the study by Khodke et al.  The study by Niazi and Raziq  has given the male to female ratio of 2:1 [Table 2]. ,,,,,,,,,
Dyspnea (50%) and easy fatigue (84%) were the common manifestations and pallor was present in all the cases [Table 3]. These findings were similar to the findings of Memon et al.  and Khodke et al.  Fever (55%) and bleeding (23%) were clinical features found in the patients in this study. Fever (47.7%) and bleeding (33.7%) were present in the patients in the study by Niazi and Raziq.  In the present study, splenomegaly was seen in 33% and hepatomegaly in 14% of the cases. The frequencies of splenomegaly and hepatomegaly were similar in various studies by Niazi and Raziq  and Khodke et al. 
Causes of Pancytopenia
In this study, the disease processes resulting in pancytopenia in the peripheral blood in order of decreasing frequency were megaloblastic anemia (66%), aplastic anemia (18%), malaria (6%), kala-azar (4%), AML (2%), multiple myeloma (2%), MDS (1%), and miliary TB (1%).
The two most common causes of pancytopenia from studies obtained from the literature search have been given in tabular form.
The findings of our study corresponds with the findings of the study done by Tilak and Jain,  Khodke et al.  and Khunger et al.  who in their studies found megaloblastic anemia 68%, 44% and 74% respectively as the most common cause of pancytopenia, followed by aplastic anemia (7.7%), (14%) and (14%). The second most common cause in this study was aplastic anemia (18%), which tallied with the figure in the study done by Khunger et al.  Memon et al.  have enumerated the most common cause of pancytopenia as aplastic anemia (23.9%), followed by leukemia (13.05%) and megaloblastic anemia (13.04%). In the present study, megaloblastic anemia (66%) was the most common cause of pancytopenia. Incidence of megaloblastic anemia varies from 0.8% to 68% in different studies. In our country, high incidence of megaloblastic anemia may be due to high prevalence of nutritional deficiencies of Vitamin B12, folic acid or both. 
Malaria (6%) was third most common cause of pancytopenia in this study. Similarly, Tilak and Jain  in their study also described malaria as the third most common cause of pancytopenia. In the study by Kumar et al.,  3% of pancytopenia was due to malaria. Kala-azar (4%) was fourth most common cause of pancytopenia in the present study. Tilak and Jain,  Khodke et al.,  Kumar et al.  has mentioned leishmaniasis as an important cause of pancytopenia. In the present study, most of these patients had migrated from endemic area (Bihar) and had presented with fever and hepatosplenomegaly.
Acute myeloid leukemia was found in 2% of the pancytopenia cases. Multiple myeloma (2%), MDS (1%) and miliary TB (1%) were other causes of pancytopenia in this study. Though these are rare causes of pancytopenia, they do occur as is mentioned in various studies by Khodke et al.,  Tilak and Jain,  Kumar et al.,  Bajracharya et al. 
In the present study, 66% cases with pancytopenia were diagnosed as megaloblastic anemia and was the most common cause of pancytopenia while in other similar studies it varied from 0.8% to 80%.  The study conducted in Malaysia found the incidence of megaloblastic anemia to be 64% and was the most common cause of pancytopenia.  The high prevalence of nutritional anemia in India has been cited for increase in frequency of megaloblastic anemia.  Khanduri and Sharma  in their study found pancytopenia with megaloblastic anemia in 62% of the cases and Gomber et al.  found 44.8% cases with bicytopenia and 1.2% cases with pancytopenia in the megaloblastic anemia group.
The age of the patients in this study varied from 5 to 80 years with mean age of 43 years. The male to female ratio was 2.7:1. 53 (82%) cases of megaloblastic anemia were vegetarian and presented with pancytopenia. However, in the study done by Khanduri and Sharma,  71% of vegetarian suffered from megaloblastic anemia. Apart from the pallor, dyspnea in 36 (54%) and fever in 29 (43%) cases were other clinical manifestations in patients of pancytopenia with megaloblastic anemia. Memon et al.  in their study have described the presenting features of megaloblastic anemia with pancytopenia as pallor with varying degree of skin and mucosal bleedings. Bleeding manifestations were seen in 23% cases in the present study. In this study, 29% case and 11% cases of megaloblastic anemia, presented with splenomegaly and hepatomegaly. Ishtiaq et al.  in their study found 15.4% and 17.9% of megaloblastic anemia with splenomegaly and hepatomegaly respectively. Likewise, hepatomegaly (66%) and splenomegaly (21%) were seen in the study done by Gomber et al.  in patients with megaloblastic anemia.
In the present study, 49 cases of megaloblastic anemia patients had macrocytic RBCs and hypersegmented neutrophils, which are the diagnostic features. Giant platelets were seen in 10 cases. Increased MCV was found in 49 patients; normal MCV was found in 13 patients and decreased MCV found in four patients with megaloblastic anemia who had iron deficiency. MCV is usually increased in severe megaloblastic anemia. Reticulocytes counts below 2% were seen in all 66 patients with megaloblastic anemia. This may be due to the abnormal maturation process. This has been cited by different studies done by Aslinia et al.  and Khanduri and Sharma.  The cellularity of bone marrow ranged from 75% to 95%. Erythroid hyperplasias with predominance of precursors were also noted in the bone marrow aspiration of the megaloblastic anemia. Giant metamyelocytes, hypersegmented neutrophils and an abnormal proliferation and maturation in the erythroid precursors with large megaloblastic erythroblasts were present in bone marrow of all patients of megaloblastic anemia.
In this study, 18% cases were diagnosed as aplastic anemia, age of the patients varied from 15 to 78 years with the mean age of 31 years. The male to female ratio was 1:1.1. These results were similar to the results of Khodke et al.  Four patients in this group were farmers and three were painters by profession who were exposed to insecticides and chemical like Benzene. These should be considered as possibilities for causing aplastic anemia as shown by the work of Snyder and Kocsis in which they have found association with aplastic anemia.  Studies from Thailand implicated pesticides as a common etiological agent for aplastic anemia. , One patient in this study had history of usage of chloramphenicol. Association between the chloramphenicol and aplastic anemia has been shown by the work of Modan et al. and Kelly et al. , Dyspnea and easy fatigue were the main complaints of patient with aplastic anemia in this study. In this study all the diagnosed case as aplastic anemia had reticulocytes counts <1%, which is a diagnostic criteria for severe aplastic anemia as mentioned by Kaufman et al. in their study.  Bone marrow aspiration may not allow reliable estimation of marrow cellularity therefore biopsy is often required in case of aplastic anemia.
Malaria was the third most common cause of pancytopenia in this study. It was present in 6% of the total cases of pancytopenia. The age group ranges from 15 to 65 years, with a male to female ratio of 1:1. Hypersplenism had been the cause of pancytopenia in all cases of malaria. Malaria related cytopenia was also noted in studies done by Latger-Cannard et al.  Malaria was second most common reason of hypersplenism producing pancytopenia, in a study done by Jain. 
In this study, 4 (4%) of the total cases of pancytopenia were diagnosed to have visceral leishmaniasis. The age group ranged from 5 to 70 years with male to female ratio of 3:1. All four patients presented with fever and hepatosplenomegaly. L.D bodies were seen in bone marrow aspirates of all the patients. The cases in this study were exposed to the endemic area (Bihar) and they had a history of fever with hepatosplenomegaly and presented as pancytopenia. Tilak and Jain  and Khunger et al.  have reported similar incidence of kala-azar-related pancytopenia.
Acute Myeloid Leukemia
In present study, 2 (2%) patients with pancytopenia had a leukemic leukemia. Both were diagnosed as AML after bone marrow examination and cytochemical staining. Pancytopenia is common in AML, as a result both of the replacement of normal bone marrow and of the defective capacity for maturation of the leukemic clone. In the studies done by Khodke et al.  and Tilak and Jain  only 1.3% cases presented with pancytopenia. The incidence of hematological malignancies presenting with pancytopenia in pediatric age group and adults was 21.4% in the study by Jha et al.  Bone marrow aspiration showed hypercellular marrow with cellularity range from 85% to 96%. Blast in the study group ranged from 30 to 40%. Auer rods More Details were seen in the blasts of both the cases. Myeloperoxidase was positive and positivity ranged from 5 to 10% of the blasts scrutinized.
In this study, 2 (2%) of the cases was diagnosed as multiple myeloma with pancytopenia. The age of patient with multiple myeloma was 56-70 years and both patients were males. Both the case had skull X-ray which showed punched out lesions. Their serum electrophoresis showed presence of paraprotein (M-band). Bence-Jones protein in urine was seen in only one case. There were 33% and 50% plasma cells in the bone marrow aspirates of these cases.
In the present study, 1 (1%) of the total case was diagnosed as MDS. It was diagnosed as refractory cytopenia with multilineage dysplasia. Bone marrow aspiration showed dysplasia in all the three cell lines, 3% blasts were seen, but ringed sideroblasts were not seen in Perls' stain.
One patient was diagnosed with miliary TB causing pancytopenia. We lost the patient during follow-up. Studies carried out by Khunger et al.  and Tilak and Jain  have also shown that pancytopenia may be seen in miliary TB.
| Conclusion|| |
Pancytopenia should be suspected on clinical grounds when a patient presents with un-explained anemia, prolonged fever and tendency to bleed. In this study, megaloblastic anemia (66%) was the most common cause of pancytopenia, followed by hypoplastic/aplastic anemia (18%). Malaria and kala-azar, which are common diseases can also present as pancytopenia. Uncommon causes of pancytopenia such as AML, multiple myeloma, MDS and tuberculosis were also diagnosed in this study. The present study concludes that detailed primary hematological investigations along with bone marrow examination in cytopenic patients is helpful for understanding disease process, to diagnose or to rule out the causes of pancytopenia. It is also useful in planning further investigations and management. A social message, which can be conveyed, is that nutritional habits of avoiding nonvegetarian diets in our country should be supplemented with regular intake of cyancobalamine and folic acid to avoid occurrence of megaloblastic anemia, which is the most common disease producing pancytopenia.
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[Table 1], [Table 2], [Table 3]