|Year : 2019 | Volume
| Issue : 12 | Page : 3944-3948
Clinico-hematological study of pancytopenia: A single-center experience from north Himalayan region of India
Harish Chandra1, Arvind K Gupta1, Uttam K Nath2, Neha Singh1, Utpal Kumar1, Sanjeev Kishore1
1 Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of Medical Oncology and Hematology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
|Date of Submission||13-Jul-2019|
|Date of Decision||22-Aug-2019|
|Date of Acceptance||10-Sep-2019|
|Date of Web Publication||10-Dec-2019|
Dr. Arvind K Gupta
Professor, Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Rishikesh - 249 203, Uttarakhand
Source of Support: None, Conflict of Interest: None
Background: Pancytopenia, an important hematological presentation is associated with different causes, which may vary in different regions. Uttarakhand, a north Himalayan state of India lacks studies of pancytopenia and the prevalent causes present in this region. Therefore, the present study was conducted to study the clinico-hematological profile of pancytopenia in a tertiary care center in the Uttarakhand, a north Himalayan state of India. It was also intended to study if these causes showed any variation from other studies done in different regions of India. Materials and Methods: The present observational study was conducted in a tertiary care institute situated in Uttarakhand state of India over a period of 1 year and 8 month from June 2017 to Feb 2019 including all the cases of pancytopenia. Results: The most common cause of pancytopenia was megaloblastic anemia (25%), followed by aleukemic leukemia and hypoplastic/aplastic anemia (19.1% each). Visceral leishmaniasis also constituted an important cause of pancytopenia in this study (11.7%). Conclusion: The study concludes that megaloblastic anemia and aleukemic leukemia are the most common cause of pancytopenia. Although leishmaniasis is considered to be non-endemic in this region, it constitutes an important cause of pancytopenia here. The clinicians, especially the physicians practicing the primary care and pathologists, should be aware of the different causes of pancytopenia present in this Himalayan region of India; therefore, delay in diagnosis can be prevented along with unnecessary investigations.
Keywords: Aleukemic leukemia, aplastic anemia, leishmaniasis, megaloblastic anemia, pancytopenia
|How to cite this article:|
Chandra H, Gupta AK, Nath UK, Singh N, Kumar U, Kishore S. Clinico-hematological study of pancytopenia: A single-center experience from north Himalayan region of India. J Family Med Prim Care 2019;8:3944-8
|How to cite this URL:|
Chandra H, Gupta AK, Nath UK, Singh N, Kumar U, Kishore S. Clinico-hematological study of pancytopenia: A single-center experience from north Himalayan region of India. J Family Med Prim Care [serial online] 2019 [cited 2021 May 7];8:3944-8. Available from: https://www.jfmpc.com/text.asp?2019/8/12/3944/272461
| Introduction|| |
Knowledge of the common differential diagnoses of any clinical finding is helpful for the treating physician in its work-up. Pancytopenia is no exception, and awareness of common causes of pancytopenia helps the clinician in the requisition of relevant tests, which would avoid potentially uncomfortable and costly procedures. However, the causes of pancytopenia show a wide variation throughout the world, and there is a need for local knowledge of the causes of this condition.,,,,,,,,, The studies of pancytopenia from Uttarakhand, a north Himalayan state of India, are limited. In addition to clinical importance, the studies from this region may also vary from the rest of India due to geographical variation and, thus, may have epidemiological importance. It is also essential that physicians practicing primary care in this region should be aware of the common prevalent causes of pancytopenia and their necessary work-up.
Hence, the present study was conducted to study the clinico-hematological profile of pancytopenia in a tertiary care center in the Uttarakhand state of India. It was also intended to study if these causes showed any variation from other studies done in different regions of India.
| Materials and Methods|| |
The present observational study was conducted after institutional ethical approval in a tertiary care institute situated in Uttarakhand state of India. The study was conducted over a period of 1 year and 8 month from June 2017 to Feb 2019 including all the cases of pancytopenia diagnosed after detailed clinical history, hemogram, peripheral smear examination, bone marrow aspiration, trephine biopsy, flow cytometry, and relevant biochemical tests. Of these, the patients with the history of chemotherapy, radiotherapy, myelosuppressive drug, and incomplete clinical details were excluded from the study. Descriptive statistics were used and the proportions and percentages of each diagnosis were calculated along with the exact 95% confidence interval by the R statistical Environment, version 3.5.1 (Vienna, Austria).
All cases having hemoglobin (Hb) less than 10 gm/dl, total leukocyte count (TLC) less than 4000/mm 3, and platelet count less than 100,000/mm 3 were defined as pancytopenia. Blood counts were done by Beckman Coulter LH-750 or Sysmex XN-1000 automated counters. The low counts were cross-checked by peripheral blood smear examination. All peripheral smears were also examined for anisopoikilocytosis, hypochromasia, presence of atypical cell, and any parasites.
Bone marrow aspiration and trephine biopsy were performed after taking informed consent under local anesthesia from posterior superior iliac spine. Immunophenotyping of cases of leukemia was done on BD FACS Canto II flow cytometer. Immunohistochemistry was also done on trephine biopsy wherever required.
| Results|| |
A total of 541 bone marrow examinations were performed in the study period and out of which 131 cases had pancytopenia. Of these 131 cases, 63 cases were excluded as they had either history of taking myelosuppresive therapy, radiotherapy, or had incomplete clinical details which could not be recovered despite best efforts. The remaining 68 cases included in the study showed male-female ratio of 1.19:1 and median age of 35 years with the range of 2–75 years. [Table 1] shows the clinical presentation of the cases of pancytopenia. It shows that hepato-splenomegaly was the most common presentation (52.9% of total cases). It was observed that median hemoglobin level was 7.2 gm/dl, TLC 2450/cumm, and platelet count 40,000/cumm. [Table 2] shows the various causes of pancytopenia with distribution according to age and sex. It shows that megaloblastic anemia [Figure 1]a was the most common cause of pancytopenia followed by aleukemic leukemia and aplastic/hypoplastic anemia [Figure 1]c. In two cases, a diagnosis could not be made even after relevant investigations. A single case of plasma cell dyscrasia was also seen presenting as pancytopenia in the present study [Figure 2]. Of the total 13 diagnosed cases of aleukemic leukemia, 5 cases were acute myeloid leukemia, 1 case was acute promyelocytic leukemia, and 4 cases were acute lymphoblastic leukemia. Remaining 3 cases were reported as acute leukemia [Figure 1]b. In addition, a total 8 case of visceral leishmaniasis were also diagnosed on bone marrow, which were cause of pancytopenia in the study [Figure 1]d. Out of these, 5 cases were residents of Uttarakhand, whereas 3 were from adjoining plains. [Table 3] shows the common causes of pancytopenia reported from various studies conducted across different regions of Indian along with their comparison with the present study.
|Table 2: Various causes of pancytopenia with distribution according to age and sex|
Click here to view
|Figure 1: (a) Bone marrow aspirate showing megaloblastic maturation of erythroid precursors in megaloblastic anemia (Wright stain, ×1000). (b) Peripheral blood smear showing myeloblasts with fine cytoplasmic granules in acute myeloblastic leukemia (Wright stain, ×1000). (c) Bone marrow trephine biopsy showing markedly hypocellular marrow with most of marrow spaces replaced by fat in aplastic anemia (H and E, ×100). (d) Bone marrow aspirate showing intracellular and extracellular Leishmania donovani bodies (Wright stain, ×1000)|
Click here to view
|Figure 2: (a) Bone marrow aspirate showing plasma cells with eccentrically placed nucleus (Wright stain, ×100) and (b) plasma cells showing perinuclear hoff (Wright stain, ×1000) in multiple myeloma|
Click here to view
|Table 3: Comparison of common causes of pancytopenia in different studies from India|
Click here to view
| Discussion|| |
In India, studies on pancytopenia from north Himalayan region of India are lacking. This data, if available, would help clinicians in planning the diagnostic approach in patients with pancytopenia and will also help in starting early treatment. Keeping this in mind, the present study was conducted to know the causes of pancytopenia at a tertiary care center in Uttarakhand, North India. With the help of detailed clinical history, physical examination, and hematological investigations, pancytopenia can be diagnosed and the causes can be ascertained. In agreement with the majority of the published studies from India, the present study also observed that megaloblastic anemia was the commonest cause of pancytopenia. This is in contrast to the Western world, where leukemia is the leading cause of pancytopenia., Hence, megaloblastic anemia should always be kept as first differential diagnosis while evaluating a case of pancytopenia in Indian settings. Thus, the data so observed in the present study would also be of immense help to physicians practicing primary care as they would be aware that megaloblastic anemia is the most common cause of pancytopenia in this region. This would be useful in avoiding irrelevant diagnostic work-ups and unnecessary financial burden on the patients. In addition, the primary care physicians, who are the first contact with the general population, may also be helpful in avoiding further complications of pancytopenia by simply preventing Vitamin B12 and folic acid deficiency. This knowledge would also help in preventing the misdiagnosis in the cases of pancytopenia due to megaloblastic anemia. Chen et al. concluded that cytopenia due to megaloblastic anemia must not be confused with myelodysplastic syndrome or erythroleukemia.
Aleukemic leukemia, hypoplastic/aplastic anemia, and visceral leishmaniasis are the other important causes of pancytopenia in the present study. Although hypoplastic/aplastic anemia has been reported as an important cause of pancytopenia in other studies from Indian subcontinent, aleukemic leukemia and visceral leishmaniasis have been rarely reported as an important cause [Table 3] Incidence of aleukemic leukemia is 19.11% in our study, which is higher than most of the study from India, and underlines the need for urgent epidemiological surveillance and public health control of this disease.,,, Kumar et al. also reported aleukemic leukemia as third most common cause of pancytopenia with overall percentage of 12.04%, which is slightly lower than our study.
Pancytopenia associated with leishmaniasis may be commonly observed in endemic regions., However, the relatively high share of pancytopenia cases due to leishmaniasis is more remarkable because Uttarakhand region is a non-endemic region for this parasitic infection.,, Recent previous reports have suggested that there is a focus of leishmaniasis at high altitude in Garhwal region of Uttarakhand , and the present findings support this contention. This may be associated with the migration of population, deforestation, or change in environmental factors.
Recent reports have observed certain rare causes of pancytopenia that include breast carcinoma, myxedema coma, or Stevens-Johnson syndrome More Details.,, Although no such cause was reported in the present study, it is necessary that clinicians and the pathologists should be aware of such rare causes of pancytopenia. Similar to our study, Le Clef et al. meticulously combined bone marrow biopsy histopathological features and blood count to achieve precise diagnosis of cytopenia. The knowledge of this approach may be helpful in avoiding diagnostic pitfalls in pancytopenia, especially by the physicians practicing primary health care.
However, an important limitation of the present study is that it is a cross-sectional observational study, done in a referral tertiary care center; therefore, the possibility of selection bias may be present and exact causes of pancytopenia prevalent in the region may not have been predicted in the study. Thus, the authors suggest that further larger studies may be done to ascertain the prevalent cause of pancytopenia in this region.
| Conclusion|| |
The study concludes that megaloblastic anemia and aleukemic leukemia are the most common causes of pancytopenia. Although leishmaniasis is considered to be non-endemic in this region, it constitutes an important cause of pancytopenia here. The clinicians, especially the physicians practicing the primary care along with the pathologists, should be aware of the different causes and morphological features of pancytopenia present in this Himalayan region of India. This knowledge will not only prevent delay in diagnosis but also unnecessary laboratory investigations which may harm both the health and pocket of the patient.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kumar DB, Raghupathi AR. Clinicohematologic analysis of pancytopenia: Study in a tertiary care centre. Basic Appl Pathol 2012;5:19-21.
Atla BL, Anem V, Dasari A. Prospective study of bone marrow in haematological disorders. Int J Res Med Sci 2015;3:1917-21.
Santra G, Das BK. A cross-sectional study of the clinical profile and aetiological spectrum of pancytopenia in a tertiary care centre. Singapore Med J 2010;51:806-12.
Raphael V, Khonglah Y, Dey B, Gogoi P, Bhuyan A. Pancytopenia–an etiological profile. Turk J Hematol 2012;29:80-1.
Mansuri B, Thekdi KP. A prospective study among cases of the pancytopenia on the basis of clinic-hematological analysis and bone marrow aspiration. Int J Res Med Sci 2017;5:3545-9.
Azaad MA, Li Y, Zhang Q, Wang H. Detection of pancytopenia associated with clinical manifestation and their final diagnosis. Open J Blood Dis 2015;5:17-30.
Ghartimagar D, Ghosh A, Thapa S, Sapkota D, Jhunjhunwala AK, Narasimhan R, et al
. Clinicohematological study of pancytopenia in a tertiary care hospital of western region of Nepal. JNMA J Nepal Med Assoc 2017;56:319-24.
Gnanaraj J, Parnes A, Francis CW, Go RS, Takemoto CM, Hashmi SK. Approach to pancytopenia: Diagnostic algorithm for clinical hematologists. Blood Rev 2018;32:361-7.
Khunger JM, Arulselvi S, Sharma U, Ranga S, Talib VH. Pancytopenia--A clinico haematological study of 200 cases. Indian J Pathol Microbiol 2002;45:375-9.
] [Full text]
Vargas-Carretero CJ, Fernandez-Vargas OE, Ron-Magaña AL, Padilla-Ortega JA, Ron-Guerrero CS, Barrera-Chairez E. Etiology and clinico-hematological profile of pancytopenia: Experience of a Mexican tertiary care center and review of the literature. Hematology 2019;24:399-404.
Chen SH, Kuo YT, Tsai LP, Liu YL, Miser JS. A 2-year-old twin boy with pancytopenia caused due to nutritional cobalamin deficiency. Pediatr Neonatol 2019. pii: S1875-9572 (19) 30149-4. doi: 10.1016/j.pedneo. 2019.06.004.
Gayathri B, Rao KS. Pancytopenia: A clinico hematological study. J Lab Physicians 2011;3:15-20.
] [Full text]
Jain A, Naniwadekar M. An etiological reappraisal of pancytopenia-largest series reported to date from a single tertiary care teaching hospital. BMC Hematol 2013;13:10.
Kumar R, Kalra SP, Kumar H, Anand AC, Madan H. Pancytopenia--A six year study. J Assoc Physicians India 2001;49:1078-81.
Dagdia K, Deshmukh AT, Soni RR, Jane DS. Haematological indices and bone marrow morphology in pancytopenia/bicytopenia. Egypt J Haematol 2016;41:23-6. [Full text]
Lupia T1, Corcione S, Boglione L, Cariti G, De Rosa FG. Visceral leishmaniasis in a patient with active HBV/HDV co-infection. J Infect Public Health 2019. pii: S1876-0341 (19) 30261-8. doi: 10.1016/j.jiph. 2019.07.026.
Cunha FT, Lopes IC, Oliveira FCS, Queiroz IT. Visceral leishmaniasis in pregnant women from Rio Grande do Norte, Brazil: A case report and literature review. Rev Soc Bras Med Trop 2019;52:e20180233.
Mathur SB, Arya AK. Nonmigrant children with visceral leishmaniasis from the nonendemic area of Uttarakhand. J Trop Pediatr 2014;60:322-5.
Chufal SS. Role of haematological changes in predicting occurrence of leishmaniasis- A study in Kumaon region of Uttarakhand. J Clin Diagn Res 2016;10:EC39-43.
Ahmad S, Chandra H, Bhat NK, Dhar M, Shirazi N, Verma SK. North Indian state of Uttarakhand: A new hothouse of visceral leishmaniasis. Trop Doct 2016;46:111-3.
Kumar A, Vinita R, Thapliyal N, Saxena SR. Kala-azar-A case series from non endemic area, Uttarakhand. J Commun Dis 2012;44:145-9.
Chandra H, Chandra S, Bhat NK, Sharma A. Clinicohaematological profile of infections in bone marrow-single centre experience in North Himalayan region of India. Hematology 2011;16:255-7.
Jindal V, Patwari A, Bhatlapenumarthi V, Siddiqui AD. Pancytopenia: A rare and unusual initial presentation of breast cancer. Cureus 2019;11:e4235.
Mupamombe CT, Reyes FM, Laskar DB, Gorga J. Myxedema coma complicated by pancytopenia. Case Rep Med 2019;2019:2320751.
Malik MN, Mujeeb Ullah A, Ahmad ME, Riaz R, Sadiq Syed TI. Pancytopenia in a patient with Stevens-Johnson syndrome: A case report with literature review. Cureus. 2019;11:e4702.
Le Clef Q, Menter T, Tzankov A. Our approach to bone marrow biopsies in cytopenia. Pathol Res Pract 2019;215:152447.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]