Pancytopenia is a condition characterized by the simultaneous occurrence of anemia (hemoglobin levels < 13 g/dL in men and < 12 g/dL in women), leukopenia (white blood cell count < 4 × 10⁹/L), and thrombocytopenia (Platelet counts < 150 × 10⁹/L).1-3 Pancytopenia is broadly classified into two categories viz Central - involving blood cells production-related disorders; and Peripheral, involving increased destruction of cells.4 Among central causes, pancytopenia is largely accounted by nutritional deficiencies leading to ineffective erythropoiesis (Vitamin B12/Folic acid deficiency) or bone marrow failure (classically referred to as aplastic anaemia; AA) whereas peripheral destruction of blood cells has been associated with various autoimmune disorders, splenic sequestration seen in conditions like liver cirrhosis, HIV, tuberculosis, and malaria. Additionally, drug induced pancytopenia and hematological malignancies (lymphoma, leukemia, or multiple myeloma) also account for pancytopenia. The typical symptoms involve generalized weakness, easy fatigability, increased infections, fever, weight loss, bleeding tendencies, shortness of breath etc with prognosis depending on the accurate and prompt diagnosis of the underlying cause.5 

The etiological spectrum of pancytopenia varies regionally. Neoplastic diseases, radiation, acute myeloid leukemia (AML) and Myelodysplastic Syndrome (MDS) were reported as common etiologies of pancytopenia from Western world 3,6,7 whereas among Asian countries, megaloblastic anemia,8-12 infections and chronic liver disease,13-14 AA, erythroid hyperplasia and infections 15,16 were found to be the most common cause of pancytopenia. Various parts of India have shown regional variation with studies from Southern and Northern India showing megaloblastic anemia,8-12, 17-19 from East showed aplastic anemia20 as predominant cause whereas a study from Western India showed hematological malignancies among the commonest causes of pancytopenia.21

Among the myriads of etiologies from pancytopenia as discussed, we planned this study at our one of the largest tertiary health care centres in Northern India. Similarly study from our own institute had shown megaloblastic anemia (MA) and aplastic anemia (AA) as major causes for pancytopenia.11 However, keeping in mind the improved socio-economic status, better hygienic conditions, and increased availability to health care with more sophisticated diagnostic modalities especially pertaining to malignancies now a days, we planned this study to explore any change in etiological spectrum of pancytopenia.

This cross-sectional study was conducted in the Department of Medicine at Pt. B. D. Sharma PGIMS, Rohtak, Haryana (INDIA) over a period of 1 year. All consecutive patients meeting the definition of pancytopenia were recruited for the study (N=162). Patients who had received/receiving chemotherapy/ radiotherapy were excluded from the study. A total of 155 patients were finally enrolled for the study. Routine haematological parameters including complete blood counts (CBC), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), Reticulocyte counts and peripheral blood film examination were done. Serum Vitamin B12 and Folic acid levels were estimated. Other relevant investigations like Bone marrow smear study and trephine biopsy, HIV status, Montoux test (intradermal injection of PPD tuberculin on flexor aspect of left forearm), ESR, chest X ray, Thyroid profile, ANA by Immunoflorescence (IFA) method, Immunophenotyping (IPT) on peripheral blood and bone marrow aspirate, ultrasound, lymph node biopsy, Computed Tomography (CT) chest and abdomen were performed according to individual clinical scenarios. A well-informed consent was taken from all patient. The Institutional Biomedical Research Ethics Committee approved the protocol (BREC/23/443/TH/Med.011dt.05.10.23). Definitions: 1. Aplastic Anemia: Aplastic anemia was defined as pancytopenia with markedly hypocellular marrow and normal marrow cell cytogenetics.22 2. Leukemia: - It was defined as a hematological malignancy in which the bone marrow & other blood forming organs produce increased number of immature leucocytes (blast cells) resulting in decreased production of normal blood cells leading to cytopenia.23 Leukemias were further classified as Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Myeloid Leukemia (CML) and Chronic Lymphoblastic Leukemia (CLL). 3. Myelodysplastic Syndrome (MDS): It was characterized by ineffective hematopoiesis, resulting in cytopenias despite a normocellular or hypercellular bone marrow. 4. Vit B12 Deficiency: It was defined when S Vit B12 levels were < 211ng/ml 5. Folic Acid Deficiency: It was defined when serum Folic acid levels were < 5.38 ng/ml. 6. Vegetarians: Vegetarian diet was defined as the practice of abstaining from the consumption of meat (meat, polutry, seafood, insects, and the flesh of any other animal and abstaining from eating all by-products of animal slaughter. 24 7. Non vegetarians: Non-vegetarian diet was as the diet containing whole or part of any animal including birds, fresh water or marine animals or eggs or products of any animal origin but excluding milk or milk product.25 Statistical Analysis The data was documented in a predesigned proforma and computer files were created in Microsoft excel for windows. Data analysis was done using STATA (StataCorp, Texas, USA). The normally distributed variables were expressed as mean ± standard deviation (SD), and continuous variables with skewed distribution as median (inter-quartile range).

Demographic Profile and Risk Factors for Pancytopenia amongst Patients

The mean age of study population was 41.05 ± 16.77 years with a M:F ratio of 1.09. 50 (32.26 %) patients had history of alcohol consumption, 8 (5.16%) were on various medications medication. 132 patients (85.16%) were following a vegetarian diet while 23 patients (14.84%) were non-vegetarian. The data has been shown in table 1.

Table 1: Demographic Profile and Risk Factors of Pancytopenia in the subjects (n=155)

General Physical and Systemic Examination:

Pallor was present in all patients with 34 (21.94%) patients had icterus. Splenomegaly and hepatomegaly were present in 61 (39.35%) and 56 patients (36.13%) respectively.  Lymphadenopathy was observed in 10 (6.45%) patients. The most common presenting complaint was weakness, reported by all patients followed by fatigue.  Bleeding manifestations were observed in 26 patients (16.78%). The data has been shown in table no 2

Table 2: General Physical and Systemic Examination finding in subjects (N=155)

Etiological Factors for Pancytopenia:

The most common cause of pancytopenia in our study was nutritional deficiency, accounting for 95 (61.29%) cases with isolated Vitamin B12 and folic acid deficiency observed in 9 (5.81%) and 4 (2.58 %) patients respectively with majority of cases [82 (52.9%)] patients having combined Vitamin B12 and folic acid deficiency. Hypersplenism was the second most common cause, amounting to pancytopenia in 32 (20.65%) patients. Only 30 (19.35%) patients underwent bone marrow examination (both aspiration and biopsy) examination. Aplastic anemia was observed in 17 (10.97%) patients. Other findings included acute leukemia (AML) in 5 (3.23%) patients, aleukemic leukemia in 1 (0.65%) patient, lymphoma in 3 (1.94%) patients and Myelodysplastic Syndrome (MDS) in 2 (1.29%) patients. 2 patients (1.29%) had normal erythroid hyperplasia. (Table 3)

Table 3: Causes of Pancytopenia in the study population (N=155)

Hematological Parameters in the study population:

The mean hemoglobin level was 5.51 ± 2.01 g/dl, total leukocyte count was 2537.23 ± 958.24 cells/mm³ with normal distribution of various cell lines.  The absolute platelet count had a mean of 56303.23 ± 34069.9/mm³. The mean corpuscular volume (MCV) was found to be 102.45 ± 16.14 fL with mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) being in normal range. The majority of patients exhibited macrocytic cells (69; 44.52%), followed by dimorphic cells (35; 22.58%), microcytic hypochromic cells (33, 21.29%), and normocytic normochromic cells (18; 11.61%). The mean Vitamin B12 level and folic acid levels were 235.06 ± 162.78 pg/mL and 5.60 ± 4.25 ng/mL respectively. The variation in levels w.r.t different causes of pancytopenia has been shown on table 4.

Table 4: Hematological Parameters, Vitamin B12 and Folic Acid levels in study population

Diagnosis and management are integral part of pancytopenia assessment as the causes range from nutritional deficiencies to the life-threatening haematological malignancies. The etiologies of pancytopenia vary in different part of world with Western world showing malignancies and MDS as predominant causes3,6,7 whereas in Eastern part it is accounted mainly by nutritional deficiencies, infections and hypersplenism with hematological malignancies to a lesser extent.8-16 Moreover, studies with in India have found different causes of pancytopenias.8-12, 20,21 With this varied etiological profile of pancytopenia, we tried to explore the causes and clinical presentation patients with pancytopenia in this study. The mean age of patients was 41.05 ± 16.77 years, with majority of cases (43.23%) belonging to younger age group. This was in contrast to our previous study reporting pancytopenia to be more common in older population (56-65 years).11 However, our findings get strength from previous other studies reporting 22-28 % of cases in younger age group (21-40) years and underscores the presence of pancytopenia in a sizeable proportion in young population. The analysis of risk factors associated with pancytopenia revealed a significant proportion of participants (32.26%) consuming alcohol, suggesting that alcohol consumption may be a potential contributor to pancytopenia, most likely secondary to nutritional deficiency of Vitamin B12. In our study, only 8 (5.16%) of patients were on any medication. Hence, with this small number we are not in position to comment on any causal relationship of medicines intake and pancytopenia. The most common symptom was generalized weakness reported in all patients followed by fatigue, fever, bleeding manifestations and pain abdomen. Among bleeding manifestations, gum bleeding and rectal bleeding were commonly reported, in addition to the presence of petechial spots, nasal bleeding and vaginal bleeding. These findings were comparable with other studies having similar clinical presentations.11,20,26-28, Patients complaining of generalized weakness and fatigue are usually treated as fibromyalgia/chronic fatigue syndrome/ functional pain and we hereby stress that these patients may be seen holistically with CBC done as initial and mandatory part of evaluation. Anemia was present in all patients as expected and manifested as pallor. Other studies have also reported pallor as the most common clinical sign of pancytopenia. 5,11,20,26,29 Icterus was observed in 34 patients (21.94%) and was more in patients having megaloblastic anemia suggesting hemolysis, a known feature of megaloblastic anemia. Significant lymphadenopathy (cervical/axillary/ inguinal) was present in 10 (6.45%) patients. This finding prompted us to evaluate patients for hematological malignancies with 11 patients (7.09 %) found to have underlying malignancy with presence of lymphadenopathy in all of them. Hepatomegaly was present in 56 (36.13%) and splenomegaly was present in 61 (39.35 %) cases. These findings were comparable with other studies reporting hepatomegaly (24-36%)5,11,20,29and splenomegaly (23-47%)1,5,11,19,20 in patients of pancytopenia. Nutritional deficiencies emerged as the leading cause of pancytopenia. Among these, the most common deficiency was a combination of vitamin B12 and folic acid deficiency, affecting 82 (52.90%) of the cohort with isolated vitamin B12 or folic acid deficiency present in only 13 patients. These findings were different from previous studies in which pure vitamin B12 deficiency was observed more commonly that pure FA deficiency or combined deficiency .2,19 Out of 95, 81 patients had either macrocytic (59; 62.1%) or dimorphic (22; 23.15%) RBCs on PBF examination further strengthened the presence of megaloblastic anemia. Both vitamin B12 and folate deficiencies cause defective cell divisions secondary to impaired DNA synthesis, thus impairing all three blood cell lines with resultant pancytopenia. This finding was comparable with other Indian studies where megaloblastic anemia was the leading cause of pancytopenia9-12,17-19 Hypersplenism was the second most common cause of pancytopenia. Hypersplenism secondary to chronic liver disease was observed in 20 (12.90%) of patients reinforcing the increased spectrum of cirrhosis of liver in society. Other causes include presence of aplastic anemia (17;10.97 %), hematological malignancies in 11 (7.09 %) patients. With this data, we emphasize that though Vit B12 and Folic acid deficiencies may be commonest causes of pancytopenia yet the occurrence of malignancies related pancytopenia cannot be overlooked and patients need to be investigated diligently. Splenomegaly was seen in 5 patients with hematological malignancies indicating its presence as a notable feature in some patients and may be attributing to significant pancytopenia. The mean hemoglobin level, TLC and platelets levels were significantly low in patients thus pointing towards pancytopenia. Peripheral blood film (PBF) revealed macrocytic cells (44.52%), followed by dimorphic cells (24.52 %) in patients. Bone marrow examination was performed in 30 (19.35%) cases with hypocellular bone marrow in 17 cases (10.97 %), indicating bone marrow failure and thus AA as cause of pancytopenia while hypercellularity was observed in 11 cases (7.09 %) and these cases were further diagnosed to hematological malignancies in 9 cases, MDS and Normocytic erythroid hyperplasia in 2 cases each. The strength of our study includes inclusion of sizeable proportion of patients. We took into account multiple parameters for assessment of pancytopenia including bone marrow examination wherever indicated. Moreover, we find the similar spectrum of etiologies as in our previous study done during 2012-13,11 a finding that was reassuring that there is no increased incidence of hematological malignancies in this region over a decade. However, we cannot extrapolate these finding to countrywide as our data is single centred.

Our study has few limitations. First, it is a single centre study from North India. Secondly, Bone marrow examination was not done in each case as previous done in other studies. Lastly, we did not follow up these patients which might have put highlight on resolution of pancytopenia, if any, with the specific therapy.

Based on above findings, we infer that pancytopenia has varied etiologies with nutritional deficiency as the most common cause of pancytopenia. We had no difference in etiological spectrum from our previous study. We hereby stress that pancytopenia should be addressed meticulously with particular emphasis to nutritional deficiencies and hematological malignancies.

1. Doshi D, Shah AN, Somani S, Jain A, Jivarajani H, Kothari P. Study of clinical and aetiological profile of 100 patients of pancytopenia at a tertiary care centre in India. Hematology. 2012 Mar 1;17(2):100-5.
2. Khunger JM, Arulselvi S, Sharma U, Ranga S, Talib VH. Pancytopenia-A Clinico
3. Haematological Study Of 200 Cases. Indian journal of pathology and microbiology. 2002 Jul 1;45(3):375-9.
4. 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 Dec;24(1):399-404.
5. Gnanaraj J, Parnes A, Francis CW, Go RS, Takemoto CM, Hashmi SK et al. Approach to pancytopenia: Diagnostic algorithm for clinical hematologists. Blood reviews. 2018 Sep 1;32(5):361-7.
6. Santra G, Das BK. A cross-sectional study of the clinical profile and aetiological spectrum of pancytopenia in a tertiary care centre. Singapore medical journal. 2010 Oct 1;51(10):806.
7. Keisu M, Ost A: Diagnoses in patients with severe pancytopenia suspected of having aplastic anemia. Eur J Haematol. 1990, 45:11-4
8. Bae MH, Cho YU, Kim B, Jang S, Park CJ, Chang YH, Kim I: Pancytopenia or bicytopenia in a Korean tertiary Care Center; etiological profile based on bone marrow examination and suggestion for diagnostic approach. Blood. 2015, 126:5610.
9. Barik S, Chandoke RK, Verma AK. A prospective clinico-hematological study in 100 cases of pancytopenia in capital city of India. Journal of applied hematology. 2014 Apr 1;5(2):45-50.
10. Bhushan D, Shukla R, Roy R, Agarwal M. Clinico-pathological profile of pancytopenia patients in a single health care centre of northern India. J Family Med Prim Care. 2022 Jun;11(6):2952-5.
11. Vardhan MV, Haveela G, Penchala B. Etiological profile of pancytopenia in a tertiary care hospital. Int J Acad Med Pharm. 2025;7(4):1221-5.
12. Ghalaut PS, Atri SK, Sharma M, Gaur N, Chahal A, Pahuja I, et al. Clinico-haematological spectrum of pancytopenia in a tertiary care centre of North India. International Journal of current research 2016 Jan; 8(01):25617-20.
13. Dubey TN, Nigotia P, Saxena R. The common causes leading to pancytopenia in patients presenting in hospital of Central India. Int J Contemp Med Res. 2016;3(10):3027-30.
14. Saadia A, Shahid A, Saeed MS, Sadiqa A, Chishti M, Fatima N. Etiological Analysis of Pancytopenia in a Tertiary Care Hospital. Annals of King Edward Medical University 2021; 27(1): 48-55.
15. Fazal W, Khan S, Akhtar R, Khattak SA, Ali M, Kakakhel M, et al. A Comprehensive Analysis of Clinical Presentations, Laboratory Findings, and Etiologies of Pancytopenia: A Tertiary Care Experience. Cureus. 2024 Nov 6;16(11):e73148.
16. Pathak R, Jha A, Sayami G. Evaluation of bone marrow in patients with pancytopenia. J Nepal Med Assoc 2012; 2:265‚Äë71.
17. Hossain MA, Akond AK, Chowdhary MK, Sikder AM, Rashid MA. Pancytopenia - A study of 50 cases. Bangladesh Journal Pathol 1992; 7:9-12.
18. Reddy GPK, Rao KVM. Clinical features and risk factors of pancytopenia: a study in a tertiary care hospital. International Journal of Advances in Medicine 2016 Feb., 3(1), 68-72.
19. Parveen R, Dhruw D, Kosam S. Clinico-Hematological Spectrum and Bone Marrow Morphology in Pancytopenia: A Hospital-Based Study. European Journal of Cardiovascular Medicine. 2025 Apr 5 ;15:136-48.
20. 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. Journal of Family Medicine and Primary Care. 2019 Dec 1;8(12):3944-8.
21. Dasgupta S, Mandal PK, Chakrabarti S. Etiology of Pancytopenia: An observation from a referral medical institution of Eastern Region of India. Journal of Laboratory Physicians. 2015;7(02):90-5.
22. Patel GR, Prajapati GR. Spectrum of pancytopenia in adults attending a clinical hematology department: a four-year experience from a tertiary care center of western India. Cureus. 2022 May 12;14(5). e24933.
23. Segel GB, Lichtman MA. Aplastic anemia. In: Lichtman MA, Kipps TJ, Seligsohn U, et al., editors. Williams hematology. 10th ed. New York: McGraw-Hill; 2021. p.563.
24. Lichtman LA. Leukemia. In: Lichtman MA, Kipps TJ, Seligsohn U, et al., editors. Williams hematology. 10th ed. New York: McGraw-Hill; 2021. p. 1343.
25. Vegetarian Society. What is a vegetarian? Vegetarian Society. [Internet]. 2018 [cited 2018 Mar 18]. Available from: https://www.vegetarian-society.org
26. Law Insider. Non-vegetarian food. [Internet]. 2023 [cited 2025 Jan 11]. Available from:
27. https://www.lawinsider.com/dictionary/non-vegetarian-food
28. Devi PM, Laishram RS, Sharma PS, Singh AM, Singh MK, Singh YM. Clinicohematological profile of pancytopenia in Manipur, India. J Kuwait Med Assoc. 2008 Sep 1; 40:221-4.
29. Kaur N, Nair V, Sharma S, Dudeja P, Puri P. A descriptive study of clinico-hematological profile of megaloblastic anemia in a tertiary care hospital. Medical Journal Armed Forces India. 2018 Oct 1;74(4):365-70.
30. Jha A, Sayami G, Adhikari RC, Panta AD, Jha R: Bone marrow examination in cases of pancytopenia. JNMA J Nepal Med Assoc. 2008, 47:12-7.
31. Rao KS. Pancytopenia: A clinico hematological study. Journal of laboratory physicians. 2011 Jan;3(01):15-20.