“ETIOPATHOLOGICAL SPECTRUM OF ANAEMIAS IN WOMEN OF REPRODUCTIVE AGE GROUP ATTENDING RRMCH, BANGALORE” By Dr. MITIKA SHRIVASTAVA Dissertation Submitted to the Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, In partial fulfilment of the requirements for the degree of DOCTOR OF MEDICINE IN PATHOLOGY Under the guidance of Dr. T .RAJARAM Professor and Head of the department DEPARTMENT OF PATHOLOGY RAJARAJESWARI MEDICAL COLLEGE AND HOSPITAL, BANGALORE 2014 i RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA DECLARATION BY THE CANDIDATE I hereby declare that this Dissertation entitled “ETIOPATHOLOGICAL SPECTRUM OF ANAEMIAS IN WOMEN OF REPRODUCTIVE AGE GROUP ATTENDING RRMCH, BANGALORE” is a bonafide and genuine research work carried out by me under the guidance of Dr. T. Rajaram., Professor and Head of the Department, Department of Pathology, Rajarajeswari Medical College and Hospital, Bangalore. The dissertation has not formed the basis for the award of any degree to me previously by any other University. Date: Dr. Mitika Shrivastava Postgraduate student, Department of Pathology Rajarajeswari Medical College and Hospital, Bangalore. Place: Bangalore ii CERTIFICATE BY THE GUIDE This is to certify that the dissertation entitled “ETIOPATHOLOGICAL SPECTRUM OF ANAEMIAS IN WOMEN OF REPRODUCTIVE AGE GROUP ATTENDING RRMCH, BANGALORE” is a bonafide research work done by Dr. MITIKA SHRIVASTAVA, Post Graduate student, in Department of Pathology, Rajarajeawari Medical College and Hospital, Bangalore. It was done under my guidance in partial fulfilment of the requirement for the M.D. in Pathology degree examination of Rajiv Gandhi University of health Science to be held in 2014. Date: Dr. T. Rajaram Professor and Head of the department of Pathology, Rajarajeswari Medical College and Hospital, Bangalore. Place: Bangalore iii ENDORSEMENT BY THE HEAD OF DEPARTMENT This is to certify that the dissertation entitled “ETIOPATHOLOGICAL SPECTRUM OF ANAEMIAS IN WOMEN OF REPRODUCTIVE AGE GROUP ATTENDING RRMCH, BANGALORE” is a bonafide research work done by Dr. Mitika Shrivastava, Post Graduate Student, in Department of Pathology, Rajarajeswari Medical College and Hospital, Bangalore, under the guidance and supervision of Dr. T. Rajaram., Professor and head of the department, Department of Pathology, Rajarajeswari Medical College and Hospital, Bangalore, in partial fulfilment of the regulations for the M..D. in Pathology degree examination of Rajiv Gandhi University of Health Science to be held in 2014. Dr. T. Rajaram Professor and Head, Department of Pathology, Rajarajeswari Medical College And Hospital, Bangalore. Date: Place: Bangalore iv Date: Place: Bangalore ENDORSEMENT BY THE HEAD OF THE INSTITUTION This is to certify that the dissertation entitled “ETIOPATHOLOGICAL SPECTRUM OF ANAEMIAS IN WOMEN OF REPRODUCTIVE AGE GROUP ATTENDING RRMCH, BANGALORE” is a bonafide research work done by Dr. Mitika Shrivastava, Post Graduate Student, in Department of Pathology, Rajarajeswari Medical College and Hospital, Bangalore, under the guidance and supervision of Dr. T. Rajaram., Professor and head of the department, Department of Pathology, Rajarajeswari Medical College and Hospital, Bangalore, in partial fulfilment of the regulations for the M..D. in Pathology degree examination of Rajiv Gandhi University of Health Science to be held in 2014. Dr. H. Rangappa Dean, Rajarajeswari Medical College and Hospital, Bangalore Date : Place: Bangalore v AKNOWLEDGMENTS Thanking is a pleasant job, but nonetheless difficult when one sincerely tries to put it in words. These humble words of expression of gratitude cannot wholly convey my feelings. I express my deep sense of gratitude to my respected teacher and guide Dr. T. Rajaram, Professor and Head, Department of Pathology, Rajarajeswari Medical College and Hospital, Bangalore who has been the propelling force and inspiration for this dissertation / research work. I am indebted to Dr. Jyothi A .Raj, Associate Professor, Department of Pathology, whose encouragement, supervision and support helped me at every step of my dissertation. It gives me enormous pleasure to express my sincere and heartfelt gratitude to Dr. Usha Ramachandra, Principal and Professor of Pathology for her support and guidance. I express my heartfelt thanks to the Dr. D. L. Ramachandra Medical Director, Dr. H. Rangappa Additional Medical Director, Dr (Gen) S.C. Godara, Dean of the Hospital, Dr. K.M. Govindaraju, Medical Superintendent and Administrative officers of Rajarajeswari Medical College and Hospital for providing the necessary facilities during my study without which this task could not have been accomplished. I express my thanks to the Chairman and the Management of Rajarajeswari Medical College and Hospital, Bangalore. vi My sincere thanks to Dr. Sharmila P.S and Dr. Mahanthachar V, Professors of Pathology, Dr. Sushma T.A, Associate Professor of Pathology, Dr. K. Shashikala and Dr. Shwetha J, Assistant Professors of Pathology and Dr. Latha V, Blood Bank Officer, for their encouragement , guidance and support during my postgraduate course. I would like to thank my colleagues Dr. Nikitha, Dr. Ankur, Dr. Paul, Dr. Dhaval, Dr. Amit, Dr. Jeena for their help and support. I am grateful to the patients who despite their suffering cooperated in completing the project. My sincere thanks to the Technical Staff of Department of Pathology, Rajarajeswari Medical College and Hospital, Bangalore. I thank Dr. Rahul Jain, my Husband for his unlimited love, faith and encouragement. I thank my in – laws and brother for their kind support. My deepest gratitude to my parents for their constant help, support, encouragement and motivation. It is to them that I dedicate this dissertation. Above all I am thankful for the divine blessings of GOD. Dr. Mitika Shrivastava Date : Place : Bangalore vii RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE. COPY RIGHT DECLARATION BY THE CANDIDATE I hereby declare that the Rajiv Gandhi University of Health Sciences, Karnataka shall have the rights to preserve, use and disseminate this dissertation in print or electronic format for academic/research purpose. Dr. Mitika Shrivastava Date: Place: Bangalore © Rajiv Gandhi University of Health Sciences, Karnataka viii LIST OF ABBREVIATIONS Hb - Haemoglobin BMI - Body mass index WHO - World Health Organisation Yrs - Years MCV - Mean Corpuscular Volume RDW - Red Cell Distribution Width HMP - Hexose Mono Phosphate IDA - Iron Deficiency Anaemia CLL - Chronic Lymphocytic Leukaemia RNA - Ribonucleic Acid NFHS - National Family Health Survey CDC - Centers for Disease Control and Prevention HIV - Human Immunodeficiency Virus NSAIDS - Nonsteroidal anti - inflammatory drug MCHC - Mean Corpuscular Haemoglobin Concentration ix TLC - Total Leucocyte Count PCV - Packed Cell Volume EDTA - Ethylene Diamine Tetra Acetic Acid AHG - Anti Human Globins Hct - Haematocrit ANOVA - Analysis of Variance IPD - In Patient Department OPD - Out Patient Department RRMCH - Rajarajeswari Medical College and Hospital AIDS - Acquired Immunodeficiency Syndrome SD - Standard Deviation WBC - White Blood Cell x ABSTRACT Background and objectives of the study Anaemia is the common problem among the reproductive age group of women in our country. The major cause is nutritional, on which extensive studies and published works are available. The pregnant and non pregnant women can have non nutritional causes of anaemia. The small possible number of haemoglobinopathies among them also need to be identified. The aim is to identify and evaluate cases of anaemia among this group and to find out the proportion of nutritional anaemias and hemolytic anaemias among this group. Methodology 1000 cases of reproductive age group women with low hemoglobin were included. All the hematological parameters including RDW were obtained through analyzer. Peripheral smear stained with Leishman’s stain was evaluated for morphology. The cases suggestive of hemolytic anaemia were evaluated by Coombs’ test and Haemoglobin electrophoresis. Bone marrow aspiration was performed wherever required. Results Out of 1000 cases of anaemia, 798 cases (79.8%) were diagnose to have microcytic hypochromic anaemia, 76 cases (7.6%) had macrocytic anaemia, 66 cases (6.6%) had normocytic normochromic anaemia and 60 cases (6%) had dimorphic anaemia. Out of 798 cases of microcytic hypochromic anaemia, 4 cases were found to xi be Coombs’ reactive and out of 66 cases of normocytic normochromic anaemia were found to have sickle cell anaemia. Conclusion Out of 1000 anaemic women identified, 994 cases were found to have nutritional anaemia and only 6 cases were diagnosed to have haemolytic anaemia. Hence, the cause of anaemia in women is non nutritional in very few. (KEY WORDS – Haemoglobinopathies, RDW, Coombs’ test) xii CONTENTS Sl.No. Title Page No. 1 INTRODUCTION 1 2 AIMS AND OBJECTIVES 5 3 REVIEW OF LITERATURE 6 4 MATERIAL AND METHODS 29 5 RESULTS 39 7 DISCUSSION 66 8 SUMMARY 75 9 CONCLUSION 77 10 REFERENCES 78 ANNEXURE PROFORMA 90 KEY TO MASTR CHART 91 MASTER CHART 92 xiii LIST OF TABLES Table No. Title Page No. Table - 1 Age distribution of patients studied 39 Table - 2 Number and percentage of women with mild, moderate and severe 40 anaemia Table - 3 Age distribution in mild, moderate and severe anaemia 41 Table - 4 Distribution of patients according to peripheral smear examination 43 Table - 5 Age wise distribution of peripheral smear 44 Table - 6 Correlation of peripheral smear with severity of anaemia 46 Table - 7 Distribution of cases according to MCV 48 Table - 8 Correlation of MCV with severity of anaemia 49 Table - 9 Distribution of cases according to MCH 50 Table - 10 Distribution of cases according to MCHC 51 Table - 11 Distribution of cases according to haematocrit 52 Table - 12 Distribution of cases according to Total RBC count 53 Table - 13 Distribution of cases according to Red cell distribution width 54 Table - 14 Correlation of RDW with severity of anaemia 55 Table - 15 Correlation of RBC count with severity of anaemia 56 Table - 16 Comparison of various variables according to severity of anaemia 57 Table - 17 Correlation of various Red cell indices with peripheral smear 58 Table - 18 Results of Coombs’ test 58 Table - 19 Bone marrow results 59 Table - 20 Electrophoresis positive cases 60 Table - 21 Age wise distribution of anaemic cases in comparison with other 69 studies xiv Table - 22 Percentage distribution of degree of anaemia in comparison with 70 other studies Table - 23 Percentage of anaemia cases with reduced MCV in comparison to 71 other studies Table - 24 Percentage of anaemia cases with increased MCV in comparison to 72 other studies Table - 25 Sensitivity of RDW in comparison with other studies xv 73 LIST OF GRAPHS Graph No. Title Page No. Graph - 1 Age distribution of patients studied 39 Graph - 2 Number and percentage of women with mild, moderate and 40 severe anaemia Graph - 3 Age distribution in mild, moderate and severe anaemia Graph - 4 Distribution of patients according to peripheral 41 smear 43 examination Graph - 5 Age wise distribution of peripheral smear 44 Graph - 6 Correlation of peripheral smear with severity of anaemia 46 Graph - 7 Distribution of cases according to MCV 48 Graph - 8 Correlation of MCV with severity of anaemia 49 Graph - 9 Distribution of cases according to MCH 50 Graph - 10 Distribution of cases according to MCHC 51 Graph - 11 Distribution of cases according to haematocrit 52 Graph - 12 Distribution of cases according to Total RBC count 53 Graph - 13 Distribution of cases according to Red cell distribution width 54 Graph - 14 Correlation of RDW with severity of anaemia 55 Graph - 15 Correlation of RBC count with severity of anaemia 56 xvi LIST OF FIGURES Figure No Title Page No. 1. Mindray BC 3000 semiautomated hematology analyser 61 2. Microcytic Hypochromic Anaemia showing microcytes 61 and a small lymphocyte 3. Microcytic Hypochromic Anaemia showing many Target cells. 62 4. Microcytic 62 Hypochromic Anaemia exhibiting marked anisopoikilocytosis., tear drop cells and target cells 5. Macrocytic Anaemia showing macrocytes and ovalocytes 63 6. Macrocytic 63 Anaemia A hypersegmented neutrophil showing and a macrocytes, small lymphocyte for comparison with RBC’S 7. Dimorphic Anaemia showing macrocytes, microcytes and a small 64 lymphocyte for comparision with RBC’S. 8. Dimorphic Anaemia showing macrocytes and microcytes. 64 9. Haemoglobin alkaline electrophoresis report showing presence of 65 HbS haemoglobin 10. Bone marrow aspirate shows megaloblasts and mitosis xvii 65
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