AIM OF THE STUDY: To assess the frequency of etiological causes of pancytopenia in North Coastal Andhra Pradesh. OBJECTIVE OF THE STUDY : 1. To study the clinical prole of a patient with pancytopenia. 2. To study the incidence of underlying etiology of the pancytopenia by Investigating Ÿ Clinical Features Ÿ Haemogram parameters Ÿ serum ferritin, vitamin B12 levels Ÿ bone marrow aspiration and biopsy MATERIALS AND METHODS STUDY DESIGN This is a prospective descriptive study done in Department of General Medicine King George Hospital from July 2017 to June 2019. All the patients with pancytopenia seen in Haemogram will be evaluated for the cause of Pancytopenia and clinical history, required tests available in our institution will be done as per proforma. SAMPLE SIZE Total of 260 cases of pancytopenia as seen in Haemogram are studied. Of which 148 cases had Bone marrow aspiration. INCLUSION CRITERIA 1) Patients aged >= 16 years of both sexes diagnosed with pancytopenia on Haemogram 2) Haemoglobin levels less than 10 g/dL 9 3) Total Leukocyte count less than 3.5 x 10 /L 9 4) Platelet Count less than 1.0x10 /L EXCLUSION CRITERIA 1) Patients aged 15 years and less 2) Diagnosed case of Pancytopenia 3) Patients who received Chemotherapy or Radiotherapy 4) Patients with Recent Viral illness – Dengue fever OBSERVATIONS AND RESULTS DEMOGRAPHICS OF THE STUDY POPULATION AGE AND SEX: The age of the study population ranged from 16 years to 85 years with a mean age of 39.8 years and median age of 37 years. Majority of the population belonged to age group of 20 – 30 years Table 2 Figure 4 The sex distribution of study population is 75 males and 73 females. There is no signicant difference in the distribution of disease in either population.   Table 3 Figure 5 Etiological distribution Of the 148 cases of Pancytopenia which underwent Bone marrow examination, 129 cases had a denitive diagnosis. Most of the cases of Pancytopenia are due to Megaloblastic Anaemia followed by Aplastic Anaemia. Other causes included, Malaria, HIV, Tuberculosis, Leukemias, Hypersplenism, Myelodysplasia and Myelobrosis. A single case of HLH is reported. Table 4 TO ASSESS THE FREQUENCY OF ETIOLOGICAL CAUSES OF PANCYTOPENIA IN NORTH COASTAL ANDHRA PRADESH. Original Research Paper Dr Malla Phanindra Final Year Post Graduate, Junior Resident, Department Of General Medicine, King George Hospital , Andhra Medical College ,Visakhapatnam, Ap, India. General Medicine KEYWORDS : Dr Gorijavolu Mamatha* Final Year Post Graduate, Junior Resident , Department Of General Medicine, King George Hospital , Andhra Medical College , Visakhapatnam, Ap, INDIA. *Corresponding Author Dr Lakshmi Sowjanya Assistant Professor , Department Of General Medicine , King George Hospital , Andhra Medical College, Visakhapatnam, Ap,india. VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra Age Group No. Of Cases <20 18 20-30 35 31-40 32 41-50 25 51-60 26 61-70 8 71-80 3 >80 1 Gender No. of cases Percentage Male 75 51 Female 73 49 Diagnosis No. of cases AML 9 Aplastic Anaemia 16 66 X GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS Figure 6 Of the Megaloblastic Anaemia, B12 deciency is the comm onest and combined folate and B12 decency is the next common cause. Table 5 Figure 7 Mean age of presentation is in the middle aged population. Oldest is seen in AML and youngest is in HIV individuals. Table 6 Distribution of gender in various causes of pancytopenia seen in the study Table 7 Figure 8 Figure 9 Figure 10 CLINICAL ANALYSIS:- SYMPTOMS:- Most of the patients had symptoms like Exertional fatigue, Petechial rash, Bleeding manifestations, Pedal edema, Fever, Frequent respiratory and Skin infections and Bone Pains. Most common symptom being exertional fatigue which is seen in 83.1 % of the cases. Next most common symptom is fever which was seen in 49%. Table 8 SIGNS:- On thorough clinical examination, most commonly seen signs with diagnostic importance are Pallor, Icterus, Lymphad enopathy, Pedal edema, Hepatomegaly, Splenomegaly, Bony tenderness, Hyper pigmented knuckles, melena. Pallor is the most common sign elicited. VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra Megaloblastic Anaemia 65 HIV 6 HLH 1 Hypersplenism 13 Malaria 8 MDS 5 Myelobrosis 2 Others 19 Tuberculosis 4 Grand Total 148 Megaloblastic Anaemia No. Of cases B12 Deciency 43 Combined B12 and Folate deciency 15 Folate deciency 7 Diagnosis Mean Age of Presentation AML 50 Aplastic Anaemia 42 Megaloblastic Anaemia 39 HIV 32 Hypersplenism 38 Malaria 37.5 MDS 44 Myelobrosis 45 Others 32.5 Tuberculosis 40.75 Diagnosis % Male %Female AML 55.5 44.5 Aplastic Anaemia 43.75 56.25 HIV 50 50 Hypersplenism 46 54 Malaria 50 50 MDS 40 60 Megaloblastic Anaemia 55.4 44.6 Myelobrosis 50 50 Others 47.3 52.7 Tuberculosis 25 75 Symptom Number of patients Percentage Fatigue 123 83.1 Fever 73 49.3 Bleeding 35 23.6 Purpuric rash 25 16.8 Bone Pain 13 8.7 Frequent infections 43 29 X 67GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS Figure 11 Figure 12 Hematological and Laboratory Findings For every case of pancytopenia, a Haemogram with peripheral smear along with HIV, Smear for Malarial parasite and Bone marrow aspiration is done. In patients with dry tap, Bone marrow biopsy is done to conrm the cause. Table 11 Table 12 Table 13 Most of the peripheral smear ndings of RBC were dimorphic followed by microcytic RBC. Table 14 Bone marrow cellularity showed hypercellular marrow in most of the aspiration ndings. The next common is normocellular marrow. 5 of the cases had drytap for which Bone marrow biopsy was done as part of further evaluation. Table 15 VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra Sign Number of Patients Percentage Pallor 146 98.6 Lymphadenopathy 24 16.2 Pedal edema 19 12.8 Hepatomegaly 18 12.1 Splenomegaly 35 23.6 Table 9 Bone pains were seen in 44.4% of AML patients and 40% of Myelodysplastic syndrome which was less than 10% in other causes. Bleeding manifestations were most commonly seen in patients with hypersplenism. Recurrent skin and respiratory tract infections were more common in Aplastic Anaemia, Myelodysplastic syndrome and HIV. Icterus was most commonly associated with malaria. It was seen in 62.5% of cases. Lymphadenopathy was frequently seen in Tuberculosis and HIV. Symptoms Aplastic Anaemia Megaloblastic Anaemia AML HIV Hypersplenism Malaria MDS Myelobrosis Others TB Total 9 16 65 6 13 8 5 2 20 4 Fatigue 100 81.25 83 100 70 87.5 40 50 90 100 Table 10 Fever 66.6 43.75 38.5 100 38.5 87.5 60 50 53 75 Bleeding 22.2 25 23 16.6 38.5 25 0 0 21 50 Purpuric rash 11.1 18.75 17 33.3 38.5 12.5 0 0 10.5 0 Bone pains 44.4 6.25 4.6 0 7.6 0 40 0 0 0 Infections 22.2 43.75 29 100 23 0 40 0 15.7 25 Pallor 100 100 98.5 100 92.3 100 100 100 100 100 Icterus 33.3 6.25 23 33.3 46 62.5 20 0 0 25 Lymphadenopathy 22.2 18.75 10.7 50 15 0 0 0 15.8 100 Pedal Edema 33.3 6.25 10.7 16.6 15 12.5 0 0 15.8 25 Hepatomegaly 11 0 13.8 0 38.5 25 0 0 0 0 Splenomegaly 22.2 6.25 18.5 0 100 87.5 0 0 0 0 Diagnosis Hb TC Platelets MCV MCH MCHC AML 3.9 2566 26667 90.25 29.7 31.7 Aplastic Anaemia 4.725 2173 32063 95.42 31.12 32.7 Megaloblastic Anaemia 4.5 2438 43100 102.7 29.5 31 HIV 5.25 2572 44500 80 27.8 33.2 Hypersplenism 4.9 2431 42154 81 24 27.6 Malaria 4.78 1910 42375 92 27.5 30.5 MDS 4.76 2128 40200 90.2 29.1 28.7 Myelobrosis 4.1 1850 26000 99 32.65 32.7 Others 5.2 2714 42579 78 23.6 29 Tuberculosis 4.95 2355 54000 80 25.7 29.5 Diagnosis B12 Folate Ferritin AML 432 18 60 Aplastic Anaemia 307 18 50 Megaloblastic Anaemia 145 8.9 37 HIV 672 7.1 64.7 Hypersplenism 736 14.3 37.46 Malaria 690 14.5 56.25 MDS 449 10.4 53.6 Myelobrosis 287 19 93 Others 420 11.7 52.9 Tuberculosis 340 10.75 22.75 Megaloblastic Anaemia MCV B12 levels Folate levels Ferritin B12 deciency 102 110 13 42 Folate deciency 110 458 0.63 34 Combine B12 and Folate Deciency 100.5 100 0.97 25 Peripheral smear nding No. of cases Normocytic 20 Microcytic 41 Macrocytic 16 Dimorphic 71 Bone marrow Cellularity No. of cases Normocellular 37 68 X GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS Figure 13 DISCUSSION Frequency of etiologies of pancytopenia varied in different population groups. This can be attributed to multiple factors such as diagnostic criteria, geographical distribution, follow up, genetic factors, infectious diseases in that particular area and exposure to drugs. Denition of pancytopenia itself is very vague as the cut-off values varied in various institutions. In our study male and female distribution is more or less similar in frequency and etiological causes. Total of 148 cases (n=148) were studied. All the cases t the criteria taken into the study. Haemoglobin<10g%, WBC Total Count<4000/cu-mm, Platelets < 100,000/cu-mm. Haemogram, Peripheral smear, Bone marrow examination, B12 levels, Folate levels, Smear for malarial parasite, HIV, Ultrasound examination were done apart from thorough history taking and clinical examination. Most common age of presentation is the third decade (35 cases) which correlated with other studies like Arvind Jain et 38 39 40al , Khunger et al and Khodke et al .Male female ratio in the present study is 1.03 which is concordant with some of the indian studies. Table 16 In our study most common cause for pancytopenia is Megaloblastic Anaemia with 65 cases (43.9%) The next common causes were Aplastic Anaemia with 16 cases (10.8%) and Hypersplenism with 13 cases (8.7%). 19 cases (12.83%) in our study couldn't be attributed to any cause due to lack of further diagnostic modalities. Megaloblastic Anaemia is the most common cause of pancytopenia in our study. It is seen in 43.9% of the cases. This is in concordance with studies of Khodke et al, Khunger et al, Tilak et al, Premkumar M et al, and Gayathri et al. Whereas in studies of Varma et al, Kumar et al, Santra et al Aplastic Anaemia is the most common cause.Zhou RH et al. stated that biopsy specimen will be more informative than an aspiration cytology regarding marrow cellularity, inltration, residual hemopoietic cells, qualitative and quantitative abnormalities of megakaryocytes showing myelodysplastic features in AML cases. Table 17 Most common Symptom seen in present study is fatigue (83.1%), followed by fever(49.3%). Most common sign is pallor(98.6%) followed by splenomegaly(23.6%). Tejaswini et al52 had fever as the most common symptom which is seen in 30.66%of cases whereas sithwath hyat et al study showed fatigue (97.64%) as the most common symptom and pallor(97.64%) as the most common sign which correlated with the present study. Gupta et al had fever as the most common symptom which was seen in 64.28% fatigue was seen in only 34.28%. Table 18 Hypocellular 16 Hypercellular 90 Dry tap 5 Study Male:Female Ratio Kumar et al41 2.1 Khunger et al39 1.2 Santra G et al42 1.5 Gayathri B N et al43 1.2 Vandana et al44 0.83 Present study 1.03 Study Country No. of cases Most common cause nd 2 most common cause International agranulocytosis and aplastic Anaemia study 48group Israel &Europe 1987 319 Aplastic Anaemia (52.7%) MDS(4.5%) 49Keisu and Ost Israel and Europe 1990 100 Neoplastic disease, Radiation (32%) Aplastic anaemia(1 9% 40Khodke et al . India 2000 50 Megaloblastic Anaemia (44%) Aplastic anaemia (14) 41Kumar et al India 2001 166 Aplastic Anaemia (29.51) Megalobla stic anaemia (23%) 39Khunger et al India 2002 Megaloblastic Anaemia (72%) Aplastic Anaemia(2 3%) 62Premkumar India 2008 140 Megaloblastic Anaemia (60.7%) Leukemia (9%) Aplastic anaemia (8%) 42Santra et al India 2010 111 Aplastic Anaemia (22%) Hypersple nism (11%) 43Gayatri et al India 2011 104 Megaloblastic Anaemia (71.04) Aplastic anaemia(1 8.26) Rashmi Kushwaha et 50al India 2012 60 Aplastic Anaemia (38.3) Megalobla stic anamia (21.7%) 51Sweta et al India 2014 100 Megaloblastic Anaemia (66%) Aplastic Anaemia (18%) 52Tejaswini et al India 2015 75 Megaloblastic Anaemia (56%) Aplastic Anaemia (13.3%) Present study India 2018 148 Megaloblastic Anaemia (43.7%) Aplastic Anaemia (10.8%) Clinical feature Tejaswini 52et al Sitwat hayt et 53al Gupta et 54al Khodke 40et al Present study Fatigue 28% 97.64% 34.28% 83.1% Fever 30.66% 52.94% 64.28% 49.3% Bleeding 8% 50.58% 34.28% 28% 23.6% Bone pains 44.7% 41.42% 2% 8.7% Splenomegaly 37.33% 55.29% 40% 23.6% Pallor 25.3% 97.64% 100% 98.6% icterus 2.66% 8.23% 23% VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra X 69GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS Haemoglobin percentage varied from 2 to 8g%. Lowest Haemoglobin was recorded in a case of Megaloblastic Anaemia. Total Leukocyte count was in a range of 500 to 3800 /cu-mm with maximum cases falling in the range of 1500 – 2500 /cu-mm. Platelet counts ranged from 10,000 to 1 lakh /cu- mm with most number of cases between 20,000 and 30,000 / cu-mm. The predominant peripheral smear picture was dimorphic Anaemia seen in 47.97% of cases and followed by Microcytic picture in 27.7%. 13.5% cases had Normocytic picture and 10.8% had macrocytic picture in peripheral smear. Gupta et al found dimorphic Anaemia in 35.7% cases, Normocytic picture in 34% cases, Microcytic in 28.57% and macrocytic in 1.43%. Most commonly seen bone marrow aspiration picture in the present study is Hypercellularity with megaloblastic picture. Gupta et al had hypocelularity as the most common nding. Swapna Kumari et al had Hyper cellularity as the most common nding in the study. Table 19 Megaloblastic Anaemia is the most Common cause (43.9%) of Pancytopenia observed in the present study. Megaloblastic Anaemia is predominantly due to B12 deciency. Combined B12 and Folate deciency is the next common cause. Of the 65 cases 43 cases can be attributed to B12 deciency alone. This accounts for 66% of Megaloblastic Anaemia cases. 7 cases are due to Folate deciency alone, which is 11%. 15 cases (23%) are due to combined deciency of folate and B12. The diagnosis of cause for megaloblastic Anaemia is made by sending serum B12 levels and Folate levels. B12 levels <200ng/ml and Folate levels<5ng/ml are taken as deciency. Table 20 Next common cause for pancytopenia in the present study is Aplastic Anaemia. Pathogenesis of Aplastic Anaemia is not well understood. Autoimmunity targeting the stem cells is thought to be the cause. This aberrant immune response is thought to be due to environmental factors, drugs, Infections and endogenous antigens. In the present study it is reported in 16 cases accounting 10.8%. This correlated with other Indian studies by Tejaswini et al, Gayathri et al, Khunger et al, Khodke et al and Swetha et al. Only few indian studies had Aplastic Anaemia as the most common cause for pancytopenia. This is evidenced in studies by Kumar et al, 42Rashmi Kushwaha et al, and Santra et al . International 48 agranulocytosis and aplastic Anaemia study group reported aplastic Anaemia(52.7%) as the most common cause of pancytopenia. This study was done in Europe and Israel. Further cause for aplastic Anaemia cannot be investigated in the present study due to lack of resources. Acute Leukemias were seen in 9 cases (6%) whereas in 39 Khunger et al reported an incidence of 5%. Prem kumar et al. (9.2%) , BN Gayathri et al. (3.85%) , compared to Kumar et al.(12%). In our study all the cases were due to AML. One of the cases we got dry tap for which a bone marrow biopsy had to be done to diagnose. Hypersplenism excluding malaria is seen in 13 cases which is 8.7 % of the cases. Peripheral pooling and destruction of the cells by enlarged spleen caused pancytopenia. Causes can be sepsis, Chronic Liver disease, infectious causes etc. The cause for hypersplenism is not included in the study. Hypersplenism is the most common cause of pancytopenia in the study by Arvind Jain et aland Hamid et al. Arvind Jain et al included Malaria in the hypersplenism group. Malaria is seen in 8 cases accounting 5.4% of the cases. Malaria causes pancytopenia by hypersplenism, hemolysis, DIC, direct bone marrow invasion by parasite and Hemophagocytosis. In the present study marrow invasion by parasite was not seen. Gupta et alreported malaria in 30% of the cases making it the most common cause for pancytopenia in that study. Hamid et al. reported 17.3% of pancytopenia cases were due to Malaria which is third most common cause. HIV caused pancytopenia in 6 cases (4%). Devi P.M. et al reported HIV in 6% of the cases in her study. Savage et aldid a study inZimbabwe which showed HIV as the third most common cause o f Pancy topenia . Hemato log ica l manifestations are diverse in HIV. They can be due to direct and indirect effects of Virus, opportunistic infections, ART therapy and associated malignancies.Tuberculosis was seen in 4 cases (2.7%) in the present study. Although TB is a rare cause of pancytopenia, it has to be considered in countries like India. It is most of the times seen in association with miliary tuberculosis. Pathogenesis of pancytopenia is not well understood. Tuberculous bacilli were not seen in all the cases of pancytopenia in tuberculosis. This hypothesizes that Anti- tuberculous drugs may also cause pancytopenia. Tuberculosis is seen in 12.5% of the cases in the study done by Arvind Jain et al and 12.86% in the study done by Gupta et al.Myelodysplastic syndrome is diagnosed by presence of dysplastic cells and Auer rods in the bone marrow. This is seen in 5 cases (3.3%) in the present study. Gupta et al reported 1.73% of the cases to be MDS. International agranulocytosis and aplastic Anaemia study group reported MDS in 4.5% nd cases making it the 2 most common cause. 2 cases of Myelobrosis were diagnosed. We got a dry tap in bone marrow aspiration. Biopsy was taken and Reticulin stain was added anddiagnosed. One case of HLH was diagnosed. This case has increased ferritin levels of 4689 ng/ml. STRENGTHS Ÿ Being a descriptive observational study, information is quick to obtain and it involved low cost. Ÿ The tests done in the study are routinely advised for pancytopenia as part of evaluation. Hence there are no ethical issues regarding that. Ÿ Multiple parameters – Clinical features, Hematological ndings, Bone marrow ndings and laboratory values are studied. Ÿ Sample size in the present study is comparatively higher than other studies done in this geographical area making it more signicant. LIMITATIONS Ÿ This study is done in a Government hospital where further diagnostic modalities are not available. Ÿ Study sample size needs to be higher for better results. Ÿ Total of 260 cases of pancytopenia were found in Haemogram. Ÿ Only 148 cases were subjected to bone marrow aspiration. These dropouts were due to fear of Bone marrow examination, and improper follow up. Ÿ Follow up of the patients after treatment needs to be monitored for further information regarding the disease lymphadenopathy 1.3% 12.94% 12% 16.2% Cellularity Gupta et al54. Swapna Kumari et al55. Present study Hypocellularity 44% 6.25 11.18 Normocellularity 12% 37.5 25.8 Hypercellularity 28% 56.25 62.93 Vitamin deciencies Akinci et al56. Prem Kumar et al62 Present study B12 deciency 58% 91.6% 66% Folate deciency 29% 5% 11% Combined deciency 12.3% 3.5% 23% VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra 70 X GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS and diagnosis. Ÿ Patients with prior Chemotherapy and Radiotherapy were excluded for convenience. Ÿ Berkesonian bias might effect the results as only patients from lower social strata attend this hospital. Ÿ Unstable Pancytopenia cases with peripheral smear showing blast cells are intentionally omitted and referred to higher centre urgently as there is no department of Hematological oncology in our hospital CONCLUSION In a prospective descriptive study “Evaluation of Pancyt openia in adults and correlation between peripheral smear and Bonemarrow Findings” done on 148 patients in Department of General Medicine, King George Hospital, the salient conclusions are rd th Ÿ Pancytopenia is more common in 3 and 4 decades Ÿ Male:Female ratio is 1.03 Ÿ Most Common cause for Pancytopenia is Megaloblastic Anaemia Ÿ second Most common cause for Pancytopenia is Aplastic Anaemia Ÿ Third most common cause is Hypersplenism Ÿ Fatigue is the most common presenting symptom followed by Fever Ÿ Pallor is the most common sign seen in pancytopenia followed by splenomegaly Ÿ Bone pains are most commonly associated with Leukemias Ÿ Tuberculosis, Malaria and HIV should be ruled out in every case of pancytopenia in our geographical region. Ÿ B12 deciency is the most common cause for megaloblastic Anaemia followed by combined B12 and Folate deciency. Ÿ Most common peripheral smear RBC nding is dimorphic Anaemia Ÿ Most common Bone marrow cellularity in pancytopenia is Hypercellularity REFERENCES 1. de Gruchy GC: Pancytopenia, aplastic Anaemia. In De Gruchy’s clinical Haematology in medical practice, 5th edition. Edited by Firkin F, Chesterman C, Penington D, Rush B. Berlin, Germany: Blackwell Science; 1989:119–36 2. Williams DM: Pancytopenia, aplastic Anaemia and pure red cell Anaemia. In Wintrobe’s clinical Haematology. 10th edition. Edited by Richard GL, Bithel TC, John F, John WA, John NL. Philadelphia: Lea and Fabiger; 1998:1449– 1489. 3. Osama I, Baqai HZ, Faiz A, Nisar H: Patterns of pancytopenia patients in a general medical ward and a proposed diagnostic approach. J Ayub Med Coll Abbottabad 2004, 16:3–7. 4. Tilak V, Jain R: Pancytopenia – a clinic hematologic analysis of 77 cases. Indian J Pathol Microbiol 1999, 42:399–404. 5. Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ, Siberstein LE. Haematology. Basic Principles and practice.3rded, USA, Churchill Livingstone; 2005. 6. Cytopenias- Anaemia, leucopenia, neutropenia, thrombocytopenia. www.oncologychannel.com/- 46K- 6/24/2007. 7. Ishtiaq O, Baqai HZ, Anwer F, Hussai N. Patterns of pancytopenia in a general medical ward and a proposed diagnostic approach.www.ayubmed.edu.pk / JAMC/PAST/16-1/osama.htm-206K- 6/24/2007. 8. Guinan EC, Shimamura A. Acquired and inherited aplastic Anaemia syndromes In: Greer JP, Foerster J, Lukens JN, Rodgers GM, Paraskevas F, Glader B Edts, Wintrobe’s Clinical Haematology,11th edn, Philadelphia :Lippincott Williams and Wilkins 2004: 1397-1419. 9. Khodke K, Marwah S, Buxi G, Yadav RB, Chaturvedi NK. Bone marrow examination in cases of pancytopenia. Journal, Indian Academy of Clinical Medicine. 2001Jan-June. 2001; 2:1-2. 10. Mobina Ahsan Dodhy, Nusrat Bokhari, Abbas Hayat. Aetiology of Pancytopenia, A ve-year experience Ann Pak Inst Med Sci 2005 Apr- Jun;1(2):92-5. 11. International agranulocytosis and aplastic anaemia study. Incidence of aplastic anaemia, the relevance of diagnostic criteria. Blood 1987; 70: 1718- 21. 12. Wintrobe MM Clinical Haematology. 8ed. Philadelphia; Lea and Febigerth 1981: 699-915. 13. Valent P. Low blood counts: immune mediated, idiopathic, or myelodysplasia. Haematology Am Soc Hematol Educ Program 2012; 2012:485. 14. Andrew Chow, Paul S. Frenette. Origin and Development of Blood Cells. Ln Greer, John P(ed). Wintrobe’s Clinical Haematology, 13th edition. Philadelphia, LIPPINCOTT WILLIAMS & WILKINS, 2014; 65-7. 15. Mohamed A. Yassin, Abdulqadir Nashwan and Shehab Mohamed. Extramedullary Haematopoiesis in Patients with Primary Myelobrosis Rare and Serious Complications. Blood 2016;128:5490. 16. Andrew Chow, Paul S. Frenette. Origin and Development of Blood Cells. Ln Greer, John P(ed). Wintrobe’s Clinical Haematology, 13th edition. Philadelphia, LIPPINCOTT WILLIAMS & WILKINS, 2014; 73-4. 17. John G. Quigley, Robert T. Means, Jr., Bertil Glader. The Birth, Life, and Death of Red Blood Cells: Erythropoiesis, The Mature Red Blood Cell, and Cell Destruction. Ln Greer, John P(ed). Wintrobe’s Clinical Haematology, 13th edition. Philadelphia, LIPPINCOTT WILLIAMS & WILKINS, 2014; 83-5. 18. G.C. de Gruchy. Formation of Blood Cells; Bone Marrow Biopsy. Ln Frank Firkin(ed). De Gruchy’s clinical haematology in clinicl practice, 5th edition. Massachusetts, Blackwell science, 1989; 5-6 VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra X 71GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS