with partial fulfilment of the regulations required for the award of degree of

A dissertation on

A CLINICAL PROFILE OF PANCYTOPENIA IN PERSON WHO CONSUMES ALCOHOL

Dissertation submitted to

THE TAMILNADU Dr M.G.R. MEDICAL UNIVERSITY CHENNAI, TAMILNADU

with partial fulfilment of the regulations required for the award of degree of

M.D. GENERAL MEDICINE BRANCH- I

COIMBATORE MEDICAL COLLEGE HOSPITAL COIMBATORE

Reg. No. 201711316

May 2020

CERTIFICATE

This is to certify that this dissertation titled “A CLINICAL PROFILE OF PANCYTOPENIA IN PERSON WHO CONSUMES ALCOHOL” has been done by Dr.SRINIVASAN. G under my guidance.

Further certified that this work is an original, embodying study of bonafide cases.

Department of Medicine,

Coimbatore Medical College Hospital, Coimbatore

Professor and Head of the Department, Dean,

Department of Medicine, Coimbatore Medical College Hospital, Coimbatore Medical College Hospital, Coimbatore

Coimbatore

CERTIFICATE - II

This is to certify that this dissertation titled “A CLINICAL PROFILE OF PANCYTOPENIA IN PERSON WHO CONSUMES ALCOHOL” of the candidate Dr.SRINIVASAN.G, with registration Number – 201711316 for the award of M.D. in the branch of General Medicine I personally verified the urkund.com website for the purpose of Plagiarism Check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 21%(TWENTY ONE) percentage of plagiarism in the dissertation.

Guide & Supervisor Sign with Seal

DECLARATION

I Dr. SRINIVASAN.G, declare that the Dissertation titled "A CLINICAL PROFILE OF PANCYTOPENIA IN PERSON WHO CONSUMES ALCOHOL" Submitted to the Dr.MGR Medical university Guindy, Chennai is an original work done by me during the academic period from JUNE 2018-JUNE 2019 at the Department of Medicine, Coimbatore Medical College Hospital, Coimbatore, under the guidance and direct supervision of Dr. K.SIVAKUMAR in partial fulfilment of the rules & regulations of the Dr.MGR Medical University for MD Medicine post graduate degree.

All the details of the patients, the materials and methods used are true to the best of my knowledge.

I assure that this dissertation has not been submitted to or evaluated by any other Medical University.

Dr. SRINIVASAN.G

ACKNOWLEDGEMENT

I wish to express my sincere thanks to our respected Dean Dr. B.ASOKAN, MCh for having allowed me to conduct this study in

our hospital . I express my heartfelt thanks and deep gratitude to the Head of department of Medicine Prof Dr K.SWAMINATHAN , MD for his generous help and guidance in the course of the study.

I’m thankful to my guide Dr.K.SIVAKUMAR, M.D for his valuable help and encouragement for doing my study.

I sincerely thank all Professors, Asst Professors. I also thank Dr.T.GEETHA M.D., Dr.RAMESH M.D., Dr.UVARAJ MURUGNANDHAM M.D.,for their guidance and kind help.

My sincere thanks to all my friends and post graduate colleagues for their whole hearted support and companionship during my studies.

I thank all my patients who formed the back bone of this study without whom this study would have not been possible.

Last but not the least I thank my parents and relatives for having

extended unconditional support throughout my life.

ABBREVIATIONS

RBC – RED BLOOD CELLS

WBC – WHITE BLOOD CELLS

HB - HEMOGLOBIN

MCV – MEAN CORPUSCULAR VOLUME

EPO – ERYTHROPOIETIN

TPO – THROMBOPOIETIN

ESR – ERYTHROCYTE SEDIMENTATION TEST

BAC – BLOOD ALCOHOL CONCENTRATION\

ABV – ALCOHOL BY VOLUME

AUDIT – ALCOHOL USE DISORDER IDENTIFICATION

TEST

AUDIT-C - ALCOHOL USE DISORDER IDENTIFICATION TEST AND CONSUMPTION SCREENING TOOL

ADH – ANTIDIURETIC HORMONE

HTN – HYPERTENSION

DM – DIABETES MELLITUS

CAD – CORONARY HEART DISEASE

RFT – RENAL FUNTION TEST

LFT – LIVER FUNCTION TEST

TABLE OF CONTENTS

S. NO. CONTENT PAGE NO.

1

1

2

2

3

3

4

5

5

35

6

70

7

74

8

75

9

76

10

78

LIST OF TABLES

S. NO. TABLE PAGE

NO.

1 Age wise distribution of the study population 35 2 Gender distribution of the study population 36 3 Distribution of study population based on dyspnoea 37 4 Distribution of patients based on fatigue 38 5 Distribution of patients based on fever 39 6 Distribution of patients based on mucosal bleeding 40 7 Classification of patients based on leg swelling 41 8 Distribution of patients based on diabetes mellitus 42 9 Classification of patients based on hypertension 43

10 Distribution of patients based on CAD 44

11 Distribution of patients based on LIVER DISEASE 45

12 Distribution of patients based on smoking 46

13 Distribution of patients based on diet 47

14 Distribution of patients based on jaundice 48

15 Distribution of patients based on lymphadenopathy 49

16 Distribution of patients based on edema 50

17 Distribution of patients based on hepatomegaly 51

18 Distribution of patients based on spleenomegly 52

19 Distribution of patients based on hepatospleenomagaly 53

20 Distribution of patients based on WBC 54

21 Distribution of patients based on HB % 55

22 Distribution of patients based on platelet count 56

23 Distribution of patients based on MCV 57

24 Distribution of patients based on ESR 58

25 Distribution of patients based on LFT 59

26 Distribution of patients based on Peripheral smear 60 27 Distribution of patients based on bone marrow HPE 61

LIST OF CHART

S. NO. CHART PAGE

NO.

1 Age wise distribution of the study population 35 2 Gender distribution of the study population 36 3 Distribution of study population based on dyspnoea 37 4 Distribution of patients based on fatigue 38 5 Distribution of patients based on fever 39 6 Distribution of patients based on mucosal bleeding 40 7 Classification of patients based on leg swelling 41 8 Distribution of patients based on diabetes mellitus 42 9 Classification of patients based on hypertension 43

10 Distribution of patients based on CAD 44

11 Distribution of patients based on LIVER DISEASE 45

12 Distribution of patients based on smoking 46

13 Distribution of patients based on diet 47

14 Distribution of patients based on jaundice 48

15 Distribution of patients based on edema 49

16 Distribution of patients based on lymphadenopathy 50

17 Distribution of patients based on hepatomegaly 51

18 Distribution of patients based on spleenomegly 52

19 Distribution of patients based on hepatospleenomagaly 53

20 Distribution of patients based on WBC 54

21 Distribution of patients based on HB % 55

22 Distribution of patients based on platelet count 56

23 Distribution of patients based on ESR 57

24 Distribution of patients based on MCV 58

25 Distribution of patients based on LFT 59

26 Distribution of patients based on Peripheral smear 60

27 Distribution of patients based on bone marrow HPE 62

LIST OF FIGURES

S. NO. FIGURES PAGE NO.

1

17

2

22

3

23

4

26

5

27

6

30

7

31

1

1.INTRODUCTION

PANCYTOPENIA is characterised by reduction in all three formed elements of blood i.e., RBC , WBC , PLATELET. Disease varies according to age, nutritional status , and geographical distribution. Treatment depends on the severity of

pancytopenia and underlying pathology. There are variety of causes for

pancytopenia , we concentrated to study about clinical profile of pancytopenia in patient who consumes alcohol. I hope this data will help to look in advance for clinical presentation of pancytopenia especially in person who consumes alcohol.

2

2.AIM OF THE STUDY

To evaluate the clinical presentations of pancytopenia particularly in persons who consumes alcohol.

3

3.MATERIAL AND METHODS

Patients admitted in GENERAL MEDICINE DEPARTMENT OF COIMBATORE MEDICAL COLLEGE HOSPITAL , COIMBATORE, fulfilling criteria for pancytopenia were evaluated. Basic personal details , relevant history , personal history has been taken. Required haematological investigations and relevant

investigations done. Peripheral smear and bone marrow examination done.

3a. STUDY DESIGN

CROSS SECTIONAL OBSERVATIONAL STUDY 3b. SAMPLE SIZE

100

3C. STUDY PERIOD

ONE YEAR ( JUNE 2018- JUNE 2019) 3d. INCLUSION CRITERIA

. PATIENTS AGE MORE THAN 21 YEARS . PERSON WHO CONSUMES ALCOHOL 3e. EXCLUSION CRITERIA

. PERSON AGE LESS THAN 21 YEARS

. PERSON WHO DOESN’T CONSUMES ALCOHOL . OTHER CAUSES OF PANCYTOPENIA

4

3f. MODE OF EVALUATION

THE WORK UP WILL INCLUDE HISTORY, PHYSICAL EXAMINATION, BLOOD INVESTIGATIONS OF PATIENTS WITH PANCYTOPENIA PARTICULARLY IN PERSON WHO CONSUMES ALCOHOL.

5

ALCOHOL ( C2H5OH )

It is a colourless volatile flammable liquid.

It is found in beer, wine and spirits that causes drunkenness.

Alcohol is made when yeast ferments (breaks down without oxygen) the sugars in different agri based products.

For eg.,

1. wine is made from the sugar in grapes

2. beer from the sugar in malted barley (a type of grain) 3. cider from the sugar in apples

4. vodka from the sugar in potatoes or beets or other plants.

Alcohol is a ‘sedative hypnotic’ drug. At higher doses alcohol acts as a depressants.

At lower doses alcohol can act as a stimulant like feelings of euphoria and

talkativeness. Consumption of too much alcohol at one time can lead to drowsiness, respiratory depression (where breathing becomes slow, shallow or stops entirely), coma or even death.

Blood alcohol concentration (BAC) over time determines the effect of alcohol in different body organs. It has both acute and chronic effects on body.

6

Types of Alcohol

In chemistry an alcohol exists when a hydroxy group, a pair of oxygen and

hydrogen atoms, replaces the hydrogen atom in a hydrocarbon. Alcohols bind with other atoms to create secondary alcohols. A secondary (2°) alcohol is one in which the carbon atom with the OH group is attached to two other carbon atoms . Its general formula is R ₂CHOH.

Three types of secondary alcohol that humans use are 1. Ethanol 2.Isopropanol 3.Methanol

The Three Types of Alcohol

Ethanol is the only type of alcohol that humans can use safely. The other two types can be used for cleaning and manufacturing purposes. Like, ethanol is a component in fuel for cars and boats. It is also used to manufacture antifreeze, paint remover, windshield wiper fluid, and many other products. The other one Isopropanol (or isopropyl alcohol), which we use for cleaning and disinfecting. If humans consumes methanol or isopropyl alcohol it will be poisonous because it metabolises as toxic substances which lead to liver injury. So consuming even a small amount of methanol or isopropanol can be fatal.

The only type of alcohol over two billion people drink daily is ETHANOL. Ethanol is produced by the fermentation of yeast, sugars, and starches. From ancient times, people have consumed ethanol-based drinks, such as beer and wine, to change their feelings. Ethanol gives feeling of relaxing the mind and body. .Ethanol also

7

hasharmful effects in the body. ONLY limited quantities of ethanol can be metabolised by liver.It damages the liver, brain and other organs over time.

There are two categories of alcoholic beverages: distilled and un distilled.

Fermented drinks are undistilled drinks. Fermentation is the process of using bacteria or yeast to chemically convert sugar into alcohol. Wine and beer are both fermented, undistilled alcoholic beverages. Fermentation of grapes to make wine as well fermentation of barley, wheat, and other grains to make beer. . Liquors and spirits are distilled alcoholic beverages .distilled beverages has more alcohol by volume than undistilled drinks. .Distillation is a process which follows fermentation.

It converts a fermented substance into one with an even higher concentration of alcohol. Distillation concentrates alcohol by separating it from the water and other components of a fermented substance. Distilled beverage has higher alcohol proof.

Measurements for alcohol content or concentration of alcohol in a drink is by 1.ALCOHOL BY VOLUME (ABV) AND 2.ALCOHOL PROOF.

1.Alcohol by volume is the number of milli litres of ethanol per 100 millilitres(or 3.4 fl.oz.) of a beverage

2.Alcohol proof is twice the percentage of alcohol by volume. For eg, a drink which has 50% ABV will be 100 proof.

Different Types of Alcoholic Drinks By Alcohol Content

There are many different kinds of alcoholic drinks, and some of them contain more alcohol than others. All alcoholic beverages carry the risk of causing health

8

problems and addiction, but drinks with higher concentrations of alcohol are able to cause drunkenness and alcohol poisoning more quickly and in smaller doses.

A. Undistilled Drinks 1.Beer

Beer is the most commonly-consumed alcoholic beverage in the world. Beer is the oldest alcoholic drink in history. A standard beer has between 4% to 6% ABV.Some beers have higher or lower concentrations of alcohol. Light beers only have between 2% to 4% ABV and malt liquors have between 6% to 8%.

2.Wine

Wine is another popular and ancient alcoholic beverage. Standard wine has less than 14% ABV. Champagne (famous sparkling wine) has an alcohol concentration of about 10% to 12%. Some wines are fortified with distilled alcohol. Examples of FORTIFIED WINES 1.Port 2.Madeira 3.Marsala 4.Vermouth 5.Sherry.ABV is 20%

in fortified wines.

3.Hard Cider

Hard cider is formed by fermentation of apple juice. ABV is about 5%.

4.Mead

Mead is formed by a blend of water and fermented honey. It has between 10% to 14% ABV.

9

5.SAKE

Sake is formed by Japanese drink made from fermented rice. ABV is about 16%.

B. Distilled Drinks (Liquors and Spirits) 1.Gin

Gin is a spirit made from juniper berries. About 35% to 55% is ABV.

2.Brandy

Brandy is distilled wine. The concentration of alcohol in brandy ranges from 35% to 60%.

3.Whiskey

Whiskey is a spirit made from distilled and fermented grain. The ABV of whiskey ranges from 40% to 50%.

4.Rum

A distilled drink made by fermenting sugarcane or molasses.It has a typical alcohol concentration of 40% ABV. Some rum is overproof meaning that it has an alcohol concentration of at least 57.5% ABV. Most overproof rum exceeds this minimum, usually reaching 75.5% ABV, which is equivalent to 151 proof.

10

5.Tequila

Tequila is another popular spirit. The Mexican agave plant is the main ingredient.

alcohol concentration is about 40% ABV.

6.Vodka

A liquor usually made from fermented grains and potatoes. It has a standard alcohol concentration of 40% ABV.

7.Absinthe

Absinthe is a spirit made from a variety of leaves and herbs. There is no evidence that absinthe is a hallucinogen. .But it has a high concentration of alcohol. Some forms of absinthe have about 40% ABV, while others have ABV as high as 90%.

8.Everclear

A grain-based spirit, is another drink with a heavy alcohol concentration. The minimum ABV of Everclear is 60%, but Everclear can also have 75.5% and 95%

ABV

ALCOHOL

. ABSOLUTE ALCOHOL -99.95% Alcohol

.RECTIFIED SPIRIT -90 TO 95% alcohol+5-10%METHANOL+TRACES OF CASTOR OIL

. METHYLATED SPIRIT – 99%ALCOHOL+ 5%WOOD NAPTHA

11

. SURGICAL SPIRIT – 90 TO 95% ETHANOL+5-10% METHANOL

.SAFETY LIMIT OF ALCOHOL : MALE-210gm/week ; FEMALE-140gm/week .ACTION : LOW CONCENTRATION- CNS STIMULANT; HIGH

CONCENTRATION-CNS DEPRESSANT

.DIAPHORESIS, DIURESIS(INHIBITS ADH), STIMULATES APPETITE.

.ALCOHOL TOO MUCH CONSUMPTION CAUSES BAD EFFECTS IN OUR BODY. SO ALWAYS HAVE SAFE LIMIT TO CONSUME ALCOHOL. BOTH GOOD AND BAD EFFECTS ARE AVAILABLE IN ALCOHOL.

BEVERAGES % OF ALCOHOL

VODKA 60-65

RUM,LIQUOR 50-60

WHISKY, GIN, BRANDY 40-45

PORT, SHERY 20

WINE, CHAMPAGNE 10-15

BEER 4-8

BLOOD LEVEL OFALCOHOL(MG%) BEHAVIOR

<10 SOBER

20-70 DRINKING

80-100 UNDER THE INFLUENCE

150-300 INTOXICATED, DRUNK

>400 COMA

12

Conc. Of alcohol in blood (mg%) SYMPTOMS

0-50 Mild euphoria

50-100 Increased confidence, impaired judgment,

nystagmus

100-150 Confusion, impaired memory, slow

reaction time

150-300 Staggering gait, increasing confusion, loss of muscle coordination

300-400 Decreased response to stimuli, stupor

>400 Deep coma, death

. URINE ALCOHOL: BLOOD ALCOHOL = 1.35:1

. WIDMARK’S FORMULA : a=PRC(BLOOD); a=3/4prq (urine) . HENRY’S LAW : ALVEOLAR:BLOOD ALCOHOL= 2100:1

. METHODS TO FIND BLOOD AND URINE ALCOHOL LEVELS .ALCOHOL DEHYDROGENASE METHOD

. KOZELKA AND HINE TEST

. GAS CHROMATOGRAPHY (MOST SPECIFIC) . BREATH ANALYSER

. CAVETT TEST

ALCOHOL IS A CNS DEPRESSANT WHEN TAKEN IN HIGH AMOUNT,IN MODERATE AMOUNT IT ACT AS CNS STIMULANT

13

ALCOHOL INDUCED THIAMINE DEFICIENCY 1.WERNICKE’S ENCEPHALOPATHY(ACUTE) 2.KORASAKOFF’S SYNDROME(CHRONIC) WERNICKE’S ENCEPHALOPATHY

.ACUTE

. GLOBAL CONFUSION . OPTHALMOPLEGIA . ATAXIA

KORASAKOFF’S PSYCHOSIS

. CHRONIC . AMNESIA

. CONFABULATION (FILLING THE MEMORY GAPS BY IMAGINARY

EVENTS)

ALCOHOL WITHDRAWAL SYNDROMES 1 . ALCOHOL HALLUCINATIONS 2 . RUM FITS

3. ALCOHOLIC KETOACIDOSIS 4. DELIRIUM TREMENS

14

ALCOHOLIC HALLUCINOSIS .ONSET :24-36 hours

. OBJECTS APPEAR DISTORTED, SHADOWS SEEM TO MOVE . TREATMENT : CHLORPROMAZINE

RUM FITS

.ONSET 7-48 HOURS

. CLONIC -TONIC MOVEMENTS ALCOHOLIC KETOACIDOSIS

. ONSET 24-72 HOURS

. DURING WITHDRAWAL OR AFTER HEAVY DRINKING . DROWSINESS, CONFUSION, INCREASED HEART RATE, . INCREASED RESPIRATORY RATE, KUSSUMAL’S

.BREATHING

. BLOOD ALCOHOL TYPICALLY NOT HIGH . HIGH ANION GAP METABOLIC ACIDOSIS . MARKEDLY ELEVATED SERUM KETONES .DELIRIUM TREMENS

. ONSET 3-5 DAYS

15

. SUDDEN WITHDRAWAL, TEMPORARY EXCESS

TRAUMA, ACUTE INFECTION MAY PRECIPITATE.

. DRAMATIC ONSET OF CLOUDING OF CONSCIOUSNESS, DISORIENTATION, LOSS OF RECENT MEMORY

. VIVID VISUAL HALLUCINATIONS

. AGITATION, RESTLESSNESS, TREMORS, ATAXIA . INSOMNIA, AUTONOMIC DISTURBANCES

. TREATMENT : DIAZEPAM

MARCHIAFAVA SYNDROME- CORPUS COLLOSUM DEGENERATION McEVAN’S SIGN – IN ALCOHOLIC COMA, PUPIL IS CONSTRICTED IF THE PATIENT IS STIMULATED BY PINCHING OR SLAPPING THE CHEEK, THE PUPILS DILATE AND SLOWLY COSTRICT. DIFFERENTIATES

ALCOHOLIC COMA FROM COMA DUE TO OTHER CAUSES

FATAL DOSE : 150ML – 250ML OF ABSOLUTE ALCOHOL TAKEN IN ONE HOUR: 60-200ML OF METHYL ALCOHOL

CAUSE OF DEATH: DEPRESSANT ACTION ON BRAINSTEM

RESPIRATORY CENTRE: ASPIRTION OF VOMITUS STATUTORY LIMIT FOR DRIVING IN INDIA : 30mg%(SECTION 185 OF

MOTOR VEHICLES ACT)

16

METHANOL

EARLY SYMPTOMS-VERTIGO,HEADACHE, STIFF NECK . LATER- OCULAR TOXICITY(FIXED DILATED PUPILS, DIMINISHED(SNOW STORM)VISION, OPTIC ATROPY) .CNS DEPRESSION IS MORE INTENSE AND PRONLOGED

.FORMIC ACID IS RESPONSIBLE FOR RETINAL TOXICITY AND HIGH ANION GAP METABOLIC ACIDOSIS

.ANTIDOTE: ETHANOL, FOMEPIZOLE . FATAL DOSE: 70-100ML

. FATAL PERIOD :1-4 DAYS

17

FIG.1 CAGE QUESTIONNAIRE

18

This is the CAGE alcoholism test. The CAGE test is straight forward TEST.

A. Have you ever thought you should Cut down on your drinking?

B. Does people talking about your drinking Annoy you?

C. Have you ever felt Guilty about your drinking?

D. Have you ever drank the next morning to get rid of HANGHOVER? (Had an Eye-opener)

1.Cut 2.Annoy 3.Guilty 4.Eye-opener

AUDIT-C Screening Tool & Overview

AUDIT-C means =The Alcohol Use Disorders Identification Test

Consumption screening tool (AUDIT-C). It is a 3 question screen that can help identify patients with alcohol misuse.

The AUDIT-C can help identify individuals who are hazardous drinkers or who have alcohol use disorders (including alcohol abuse or dependence). The AUDIT-C is a modified version of the 10 question AUDIT screening instrument.

19

QUESTIONS

A. How often do you have a drink containing alcohol?

. Never -0 SCORE

. Monthly or less -1 SCORE . 2 to 4 times a month-2 SCORE .2 to 3 times a week-3 SCORE .4 or more times a week-4 SCORE

B. How many drinks containing alcohol do you have on a typical day when you are drinking?

.1 or 2-0

.3 or 4-1 SCORE .5 or 6-2 SCORE .7, 8, or 9 – 3 SCORE .10 or more-4 SCORE

3. How often do you have six or more drinks on one occasion?

. Never -0 SCORE

.Less than monthly – 1 SCORE .Monthly-2 SCORE

20

. Weekly -3 SCORE

. Daily or almost daily- 4 SCORE Scoring and Interpretation

The AUDIT-C is scored on a scale of 0-12 points (scores of 0 reflect no alcohol use in the past year). In men - a score of 4 points or more is considered positive for alcohol misuse. 2. In women- a score of 3 points or more is considered positive.The higher the AUDIT-C score, the more likely is that the patient consumption of alcohol is affecting his/her health and safety.

21

a. AUDIT: Alcohol Use Disorders Identification Test and Guidelines

 The AUDIT is a simple questionnaire method developed by the World Health Organization (WHO) assessing alcohol consumption, drinking behaviours, and alcohol-related problem.

22

FIG.2 AUDIT SCREENING

23

FIG.3 AUDIT SCORES AND ZONES

24

PANCYTOPENIA

PANCYTOPENIA is a condition in which persons body has too few red blood cells, white blood cells, and platelets.

.ANEMIA- LOW LEVEL OF RED BLOOD CELLS

.LEUKOPENIA- LOW LEVEL OF WHITE BLOOD CELLS . THROMBOCYTOPENIA- LOW PLATELET COUNTS HEMATOPOEISIS

HEMATOPOIESIS : The formation of blood i.e.,

1. the developmental processes of the formed elements in blood

2. In the red bone marrow from the descendants of the pleuripotent hemopoietic stem cell by the processes of proliferation and differentiation

3. each stem cell can give rise to as many as 2¹¹ mature cells.

ERYTHROPOIESIS: The formation of red blood cells, i.e., 1.the developmental processes of the red blood cell

2.In the red bone marrow from the descendants of the proerythroblast stem cell by the processes of proliferation and differentiation

3.each hemocytoblast stem cell can give rise to as many as 2¹¹ mature cells.

25

STEM CELL:BLAST CELL

1. Any immature AND undifferentiated 2. unspecialized cell

3. capable of repeated cell divisions (proliferation) 4. which can replace itself and by differentiation

5. give rise to one or more specific specialized mature cell type such as blood cells.

HEMOCYTOBLAST:

PLEURIPOTENTHEMOPOEITIC STEM CELL:

1.The primordial stem cell of red bone marrow which is capable of developing into any type of blood cell.

PROERYTHROBLAST:

1.The earliest stem cell found in the red bone marrow which is committed to develop into a red blood cell.

RETICULOCYTE:

1 The final form of the immature red blood cell which is slightly larger than a mature RBC

2.It has extruded its nucleus but still contains a network of basophilic (takes up the basic blue-purple stain) filaments

3.It represent the sites (ribosomes) of final hemoglobin synthesis

26

4. primarily they are found in the red bone marrow but a few (0.2-2.0% of total RBCs) are found in the circulating blood

FIG.4 PERIPHERAL SMEAR -1 MEGAKARYOCYTE

1.The largest cell found in red bone marrow 2.It is the source of blood platelets

3.It has a characteristic appearance including a lobulate polyploid nucleus 4.It gives rise to three to four thousand platelets which are membrane-bound fragments shed from its cytoplasm into the blood circulation.

27

FIG.5 PERIPHERAL SMEAR - 2 HEMOPOIETIC GROWTH FACTOR

1.Any of the various regulatory proteins and local hormones which target the

hematopoietic stem cells in the red bone marrow which promote a. the growth b. organization and c. maintenance of red bone marrow and blood cells.

ERYTHROPOIETIN (EPO)

1. A glycoprotein hormone which stimulates the production of red blood cells by stem cells in the red bone marrow

2. It is produced mainly by the kidneys at the juxtaglomerular apparatus

3. It is released in response to decreased levels of oxygen detected in the blood in the afferent arteriole in the nephron.

28

CYTOKINES

1. Any of several regulatory proteins

2. such as the interleukins and lymphokines

3. which are local hormones (paracrines and autocrines) released by cells of the immune system

4. act as intercellular mediators in the generation of an immune response.

COLONY STIMULATING FACTOR

1.Any of several regulatory glycoproteins which are local hormones (a functional category of cytokines) released by cells of the immune system

2. act as intercellular mediators in the proliferation 3. i.e., cell divisions, of erythrocytes and leukocytes

4.These mediators are used therapeutically to enhance the success of bone marrow transplants

INTERLEUKINS

1. Any of the dozen regulatory proteins which are local hormones (a functional category of cytokines) released by a variety of cells including lymphocytes and monocytes

2. especially by T lymphocytes

29

THROMBOPOIETIN (TPO) the

1. A glycoprotein growth factor released by a. liver b. kidney c. bone marrow 2. In response to a reduction in circulating platelets

3. It targets the committed stem cells in the megakaryocyte lineage in red bone marrow to differentiate

4. proliferate so that platelet production will increase to restore homeostasis.

30

FIG.6 HEMATOPOIESIS-1

31

FIG.7 HEMATOPOIESIS-2

32

CAUSES OF PANCYTOPENIA 1.BONE MARROW FAILURE

HYPOPLASTIC / APLASTIC ANEMIA : 1.INHERITED

2.IDIOPATHIC 3.VIRAL

4.DRUGS

2.BONE MARROW INFILTRATION A. ACUTE LEUKEMIA

B. MYELOMA C. LYMPHOMA D. CARCINOMA

E. HEMOPHAGOCYTIC SYNDROMES F. MYELODYSPLASTIC SYNDROMES 3.INEFFECTIVE ERYTHROPOIESIS

A. MEGALOBLASTIC ANEMIA B. ALCOHOL

C. ACQUIRED IMMUNODEFICIENCY SYNDROMES (AIDS)

33

4.PERIPHERAL POOLING / DESTRUCTION A. HYPERSPLENISM

B. SYSTEMIC LUPUS ERYTHEMATOSUS

MECHANISM OF ALCOHOL CAUSING PANCYTOPENIA 1.direct action of alcohol over bone marrow

2.in alcoholics , nutritional deficiency(vitamin b12 and folic acid) leading to macrocytosis.

CLINICAL FEATURES 1. difficulty in breathing 2. fatigue

3. infection

4. easy bleeding -such as from gums or nose 5. easy bruising

6. tachycardia 7. pallor 8. rashes 9. weakness

34

DIAGNOSIS

1. complete blood count 2. Renal function test(RFT) 3. liver function test (LFT) 4. vitamin B-12 levels 5. HIV

6. hepatitis serology

7. bone marrow examination TREATMENT

1. Treatment of the underlying cause

2. Blood transfusion may be indicated according to need

35

Frequency Table

Table 1 : Age wise distribution of the study population

Age group ^{Frequency Percent}

20-30 Years 5 5.0

31-40 Years 37 37.0

41-50 Years 44 44.0

51-60 Years 12 12.0

Above 60 Years 2 2.0

Total 100 100.0

Chart 1 : Age wise distribution of the study population

5%

37%

44%

12%

2%

Age group

20-30 Years 31-40 Years 41-50 Years 51-60 Years Above 60 Years

36

Table 2 : Gender distribution of the study population

Gender ^{Frequency Percent}

Male 92 92.0

Female 8 8.0

Total 100 100.0

Chart 2 : Gender distribution of the study population

92%

8%

Gender

Male Female

37

Table 3 : Distribution of study population based on dyspnoea

DYSPNOEA Frequency Percent

Absent 66 66.0

Present 34 34.0

Total 100 100.0

Chart 3 :Distribution of study population based on dyspnoea

66%

34%

DYSPNOEA

Absent Present

38

Table 4 : Distribution of patients based on fatigue

FATIGUE Frequency Percent

Absent 51 51.0

Present 49 49.0

Total 100 100.0

Chart 4 : Distribution of patients based on fatigue

51%

49%

FATIGUE

Absent Present

39

Table 5 : Distribution of patients based on fever

FEVER Frequency Percent

Absent 90 90.0

Present 10 10.0

Total 100 100.0

Chart 5 : Distribution of patients based on fever

90%

10%

FEVER

Absent Present

40

Table 6 : Distribution of patients based on mucosal bleeding

MUCOSALBLEEDING Frequency Percent

Absent 91 91.0

Present 9 9.0

Total 100 100.0

Chart 6 : Distribution of patients based on mucosal bleeding

91%

9%

MUCOSAL BLEEDING

Absent Present

41

Table 7 :Classification of patients based on leg swelling

LEGSWELLING Frequency Percent

Absent 75 75.0

Present 25 25.0

Total 100 100.0

Chart 7 : Classification of patients based on leg swelling

75%

25%

LEG SWELLING

Absent Present

42

Table 8 : Distribution of patients based on diabetes mellitus

Diabetes Mellitus ^{Frequency Percent}

Absent 89 89.0

Present 11 11.0

Total 100 100.0

Chart 8 :Distribution of patients based on diabetes mellitus

89%

11%

DIABETES MELLITUS

Absent Present

43

Table 9 :Classification of patients based on hypertension

HTN ^{Frequency Percent}

Absent 89 89.0

Present 11 11.0

Total 100 100.0

Chart 9 :Classification of patients based on hypertension

89%

11%

HYPERTENSION

Absent Present

44

Table 10 :Distribution of patients based on CAD

CAD ^{Frequency Percent}

Absent 95 95.0

Present 5 5.0

Total 100 100.0

Chart 10 : Distribution of patients based on CAD

95%

5%

CAD

Absent Present

45

Table 11: Distribution of patients based on LIVER DISEASE

LIVERDISEASE Frequency Percent

Absent 85 85.0

Present 15 15.0

Total 100 100.0

Chart 11 :Distribution of patients based on LIVER DISEASE

85%

15%

LIVER DISEASE

Absent Present

46

Table 12 : Distribution of patients based on smoking

SMOKING Frequency Percent

Absent 72 72.0

Present 28 28.0

Total 100 100.0

Chart 12 :Distribution of patients based on smoking

72%

28%

SMOKING

Absent Present

47

Table 13 :Distribution of patients based on diet

DIET ^{Frequency Percent}

NON-VEGETARIAN 84 84.0

VEGETARIAN 16 16.0

Total 100 100.0

Chart 13 : Distribution of patients based on diet

84%

16%

DIET

NON-VEGETARIAN VEGETARIAN

48

Table 14 :Distribution of patients based on jaundice

ICTERUS Frequency Percent

Absent 83 83.0

Present 17 17.0

Total 100 100.0

Chart 14 : Distribution of patients based on jaundice

83%

17%

ICTERUS

Absent Present

49

Table 15 : Distribution of patients based on lymphadenopathy

LYMPHADENOPATHY Frequency Percent

Absent 96 96.0

Present 4 4.0

Total 100 100.0

Chart 15 : Distribution of patients based on lymphadenopathy

96%

4%

LYMPHADENOPATHY

Absent Present

50

Table 16 : Distribution of patients based on edema

EDEMA Frequency Percent

Absent 87 87.0

Present 13 13.0

Total 100 100.0

Chart 16 :Distribution of patients based on edema

87%

13%

EDEMA

Absent Present

51

Table 17 : Distribution of patients based on hepatomegaly

HEPATOMEGALY Frequency Percent

Absent 81 81.0

Present 19 19.0

Total 100 100.0

Chart 17 : Distribution of patients based on hepatomegaly

81%

19%

HEPATOMEGALY

Absent Present

52

Table 18 :Distribution of patients based on splenomegly

SPLEENOMEGALY Frequency Percent

Absent 77 77.0

Present 23 23.0

Total 100 100.0

Chart 18 :Distribution of patients based on splenomegly

77%

23%

SPLEENOMEGALY

Absent Present

53

Table 19 : Distribution of patients based on hepatosplenomagaly

BOTH Frequency Percent

Absent 88 88.0

Present 12 12.0

Total 100 100.0

Chart 19 : Distribution of patients based on hepatosplenomagaly

BOTH

Absent Present

54

Table 20 :Distribution of patients based on WBC

TOTAL NO SCORE Frequency Percent

<3000 44 44.0

3001 TO 4000 52 52.0

Above 4000 4 4.0

Total 100 100.0

Chart 20 :Distribution of patients based on WBC

44%

52%

4%

0%

10%

20%

30%

40%

50%

60%

<3000 3001 TO 4000 Above 4000

TOTAL COUNT

55

Table 21 : Distribution of patients based on HB %

TOTAL NO SCORE Percent

20-30 5.90

31-40 6.29

41-50 5.63

51-60 5.83

Above 60 5.85

Chart 21 :Distribution of patients based on HB %

56

Table 22 :Distribution of patients based on platelet count

PLATELETSCORE Frequency Percent

<50000 29 29.0

50001 to 75000 51 51.0

75001 to 90000 20 20.0

Total 100 100.0

Chart 22 :Distribution of patients based on platelet count

29%

51%

20%

0%

10%

20%

30%

40%

50%

60%

<50000 50001 to 75000 75001 to 90000

PLATELET SCORE

57

Table 23 : Distribution of patients based on MCV

MCVSCORE Frequency Percent

90-100 31 31.0

101-110 59 59.0

111 – 120 10 10.0

Total 100 100.0

Chart 23 : Distribution of patients based on MCV

0%

10%

20%

30%

40%

50%

60%

90-100 101-110 111 - 120

31%

59%

10%

MCV

58

Table 24 :Distribution of patients based on ESR

ESRSCORE Frequency Percent

<30 4 4.0

31-50 27 27.0

51-70 45 45.0

Above 70 24 24.0

Total 100 100.0

Chart 24 : Distribution of patients based on ESR

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

<30 31-50 51-70 Above 70

ESR

59

Table 25 : Distribution of patients based on LFT

LFT ^{Frequency Percent}

ALTERED 1 1.0

NORMAL 99 99.0

Total 100 100.0

Chart 25 : Distribution of patients based on LFT

LFT

ALTERED NORMAL

60

Table 26:Distribution of patients based on Peripheral smear

PERIPHERALSMEAR Frequency Percent

MACROCYTES 24 24.0

MACROCYTES, ELONGATED CELLS 4 4.0

MACROCYTES, TEAR DROP CELLS 17 17.0

MACROCYTES,ANISOPOIKLOCYTES 6 6.0

MACROCYTES,ELONGATED CELLS 6 6.0

MACROCYTESC, ANISOPOIKLOCYTES 4 4.0

MACROOVALOCYTES 6 6.0

MICROCYTES,MACROCYTES 33 33.0

Total 100 100.0

Chart 26 : Distribution of patients based on Peripheral smear

MACROCYTES, 24%

MACROCYTES, ELO NGATED CELLS, 4%

MACROCYTES, TEA R DROP CELLS, 17%

MACROCYTES,ANIS OPOIKLOCYTES, 6%

MACROCYTES,ELON GATED CELLS, 6%

MACROCYTESC, AN ISOPOIKLOCYTES, 4

% MACROOVALOCYTE

S, 6%

MICROCYTES,MACR OCYTES, 33%

PERIPHERAL SMEAR

61

Table 27 :Distribution of patients based on bone marrow HPE

BONEMARROW Frequency Percent

BONE MARROW HYPOCELLULAR,MEGALOBLASTS SEEN 20 20.0 CELLULAR MARROW, MEGAKARYOCYTES SEEN 5 5.0 CELLULAR, NORMAL MYELOID ERYTHROID RATIO,

MEGAKARYOCYTES SEEN 5 5.0

ERYTHROPOIESIS SEEN, MEGALOBLASTS SEEN 5 5.0 GIANT METAMYELOCYTES,GIANT BAND, MEGAKARYOCYTES 5 5.0

M:E= 1.5:3,ERYTHROID HYPERPLASIA 5 5.0

M:E=1:1, MEGALOBLASTS SEEN 5 5.0

M:E=1:2,ERYTHROPOIESIS IS ACTIVE, MEGALOBLATS SEEN 5 5.0 M:E=1:2.5-3,ERYTHROID HYPERPLASIA, DOMINANT

MEGALOBLASTS 5 5.0

M:E=1.5:1 , DOMINANT MEGALOBLASTS, OCCASIONAL

MICROCYTES 5 5.0

M:E=1.5:3-4,ERYTHROID HYPERPLASIA, MEGALOBLASTS

SEEN 5 5.0

M:E=2:1, MEGALOBLASTS SEEN 5 5.0

M:E=2:4,ERYTHROID HYPERPLASIA,MEGALOBLASTS SEEN 5 5.0

M:E=3:1.5, MEGALOBLASTS SEEN 5 5.0

M:E=3:2, MEGALOBLASTS SEEN 5 5.0

MEGAKARYOCYTES SEEN 10 10.0

Total 100 100.0

62

Chart 27 : Distribution of patients based on bone marrow HPE

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

BONE MARROW HYPOCELLULAR,MEGALOBLASTS SEEN CELLULAR MARROW, MEGAKARYOCYTES SEEN CELLULAR, NORMAL MYELOID ERYTHROID RATIO, MEGAKARYOCYTES SEEN ERYTHROPOIESIS SEEN, MEGALOBLASTS SEEN GIANT METAMYELOCYTES,GIANT BAND, MEGAKARYOCYTES M:E= 1.5:3,ERYTHROID HYPERPLASIA M:E=1:1, MEGALOBLASTS SEEN M:E=1:2,ERYTHROPOIESIS IS ACTIVE, MEGALOBLATS SEEN M:E=1:2.5-3,ERYTHROID HYPERPLASIA, DOMINANT MEGALOBLASTS M:E=1.5:1 , DOMINANT MEGALOBLASTS, OCCASIONAL MICROCYTES M:E=1.5:3-4,ERYTHROID HYPERPLASIA, MEGALOBLASTS SEEN M:E=2:1, MEGALOBLASTS SEEN M:E=2:4,ERYTHROID HYPERPLASIA,MEGALOBLASTS SEEN M:E=3:1.5, MEGALOBLASTS SEEN M:E=3:2, MEGALOBLASTS SEEN MEGAKARYOCYTES SEEN 20%

5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5%

10%

BONE MARROW

63 Descriptives

Descriptive Statistics

N Minimum Maximum Mean Std. Deviation

AGE 100 26.00 65.00 43.2400 7.76696

HB 100 3.70 9.20 5.9190 1.16582

TOTAL NO 100 1900.00 4500.00 3105.7000 554.46991

PLATELET 100 35000.00 90000.00 61290.0000 14178.72571

MCV 100 96.00 118.00 103.8900 4.80718

ESR 100 23.00 93.00 60.7500 16.61530

64

N Mean Std.

Deviation

Std. Error 95% Confidence Interval for Mean

Lower Bound Upper Bound f VALUE p VALUE

HB

20-30 Years 5 5.9000 .88034 .39370 4.8069 6.9931 1.692 0.158 31-40 Years 37 6.2946 1.13528 .18664 5.9161 6.6731

41-50 Years 44 5.6318 1.21114 .18259 5.2636 6.0000 51-60 Years 12 5.8333 .92376 .26667 5.2464 6.4203 Above 60 Years 2 5.8500 1.90919 1.35000 -11.3034 23.0034 Total 100 5.9190 1.16582 .11658 5.6877 6.1503

TOTAL NO

20-30 Years 5 2626.0000 332.23486 148.57994 2213.4759 3038.5241 2.003 0.100 31-40 Years 37 3227.0270 607.24270 99.83008 3024.5622 3429.4918

41-50 Years 44 3030.0000 498.13139 75.09613 2878.5542 3181.4458 51-60 Years 12 3255.0000 555.50959 160.36181 2902.0460 3607.9540 Above 60 Years 2 2830.0000 537.40115 380.00000 -1998.3578 7658.3578 Total 100 3105.7000 554.46991 55.44699 2995.6811 3215.7189

PLATELET

20-30 Years 5 50400.0000 6308.72412 2821.34720 42566.6844 58233.3156 3.061* 0.020 31-40 Years 37 61324.3243 13587.27766 2233.73469 56794.1004 65854.5482

41-50 Years 44 61045.4545 14638.20193 2206.79197 56595.0344 65495.8747 51-60 Years 12 69916.6667 12011.04290 3467.28943 62285.2141 77548.1192 Above 60 Years 2 41500.0000 4949.74747 3500.00000 -2971.7166 85971.7166 Total 100 61290.0000 14178.72571 1417.87257 58476.6332 64103.3668

MCV

20-30 Years 5 101.4000 2.30217 1.02956 98.5415 104.2585 1.748 0.146 31-40 Years 37 105.1351 5.86497 .96420 103.1797 107.0906

41-50 Years 44 103.7500 4.19925 .63306 102.4733 105.0267 51-60 Years 12 102.3333 3.20038 .92387 100.2999 104.3668 Above 60 Years 2 99.5000 .70711 .50000 93.1469 105.8531 Total 100 103.8900 4.80718 .48072 102.9362 104.8438

ESR

20-30 Years 5 62.6000 17.75669 7.94103 40.5522 84.6478 1.743 0.147 31-40 Years 37 57.7297 17.22506 2.83178 51.9866 63.4729

41-50 Years 44 62.0682 16.14383 2.43377 57.1600 66.9764 51-60 Years 12 60.0000 14.49765 4.18511 50.7886 69.2114 Above 60 Years 2 87.5000 .70711 .50000 81.1469 93.8531 Total 100 60.7500 16.61530 1.66153 57.4532 64.0468

65 0

10000 20000 30000 40000 50000 60000 70000

20-30 Years 31-40 Years 41-50 Years 51-60 Years Above 60 Years 50400

61324 61045

69917

41500

PLATELET

66

Crosstab

AGE_GROUP Total

20-30 Years

31-40 Years

41-50 Years

51-60 Years

Above 60 Years

PERIPHERAL_SM EAR

MACROCYTES

No 1 8 12 3 0 24

% 4.2% 33.3% 50.0% 12.5% 0.0% 100.0%

MACROCYTES, ELONGATED CELLS

No 1 1 2 0 0 4

% 25.0% 25.0% 50.0% 0.0% 0.0% 100.0%

MACROCYTES, TEAR DROP CELLS

No 1 7 5 4 0 17

% 5.9% 41.2% 29.4% 23.5% 0.0% 100.0%

MACROCYTES, ANISOPOIKLOCYTES

No 0 4 2 0 0 6

% 0.0% 66.7% 33.3% 0.0% 0.0% 100.0%

MACROCYTES, ELONGATED CELLS

No 0 2 4 0 0 6

% 0.0% 33.3% 66.7% 0.0% 0.0% 100.0%

MACROCYTESC, ANISOPOIKLOCYTES

No 0 0 3 1 0 4

% 0.0% 0.0% 75.0% 25.0% 0.0% 100.0%

MACROOVALOCYTES

No 0 0 4 2 0 6

% 0.0% 0.0% 66.7% 33.3% 0.0% 100.0%

MICROCYTES, MACROCYTES

No 2 15 12 2 2 33

% 6.1% 45.5% 36.4% 6.1% 6.1% 100.0%

Total

No 5 37 44 12 2 100

% 5.0% 37.0% 44.0% 12.0% 2.0% 100.0%

Pearson Chi-Square=26.140 P=0.565

0%

10%

20%

30%

40%

50%

60%

70%

80%

4%

25%

6% 6%

33% 25%

41%

67%

33%

50% 50% 46%

29% 33%

67% 75%

67%

36%

13%

24% 25% 33%

6%6%

20-30 Years 31-40 Years 41-50 Years 51-60 Years Above 60 Years