I Dr. ADHIKESAVSAN.P, declare that the Dissertation titled "

A dissertation on

A STUDY ON HAEMATOLOGICAL ABNORMALITIES

INDECOMPENSATEDCHRONIC LIVER DISEASE IN COIMBATORE MEDICAL COLLEGE HOSPITAL

Dissertation submitted to

THE TAMIL NADU Dr M.G.R. MEDICAL UNIVERSITY CHENNAI, TAMIL NADU

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

M.D. GENERAL MEDICINE BRANCH- I

COIMBATORE MEDICAL COLLEGE, COIMBATORE

Reg No. 201711302 May 2020

CERTIFICATE

This is to certify that this dissertation titled “A STUDY ON HAEMATOLOGICAL ABNORMALITIES IN DECOMPENSATED CHRONIC LIVER DISEASE PATIENTS IN COIMBATORE MEDICAL COLLEGE HOSPITAL” has been done by Dr.ADHIKESAVAN. P 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 STUDY ON HAEMATOLOGICAL ABNORMALITIES IN DECOMPENSATED CHRONIC LIVER DISEASE PATIENTS IN COIMBATORE MEDICAL COLLEGE HOSPITAL” of the candidate Dr. Adhikesavan. P, with registration Number – 201711302 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 22%(Twenty two) percentage of plagiarism in the dissertation.

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DECLARATION

I Dr. ADHIKESAVSAN.P, declare that the Dissertation titled "

"Submitted to the Dr.MGR Medical university Guindy, Chennai is an original work done by me during the academic period from January 2018-December 2018 at the Department of Medicine, Coimbatore Medical College Hospital, Coimbatore, under the guidance and direct supervision of Dr.SWAMINATHAN.Kin 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.ADHIKESAVAN P

Post graduate student

Department of General Medicine

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 owe a great debt of gratitude to our respected Professor and unit chief

Prof. Dr. KUMAR NATARAJAN, M.D, retired Head of the Department of Medicine, Coimbatore Medical College.

I sincerely thank Professors and Asst. Professors Dr.VISHNU RAM M.D, Dr. AVUDAIYAPPAN M.D, Dr.KARUPPUSAMY M.D, and Dr.SANGEETHA 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

AST -

Aspartate Transaminase

Alanine Transaminase

Red blood cell

WBC -

White blood cell

Prothrombin time

aPTT -

Activated partial thromboplastin time

International normalized ratio

DIC -

Disseminated intravascular coagulation

Von willebrand factor

HBV -

Hepatitis B virus

Hepatitis C virus

HCC -

Hepatocellular Carcinoma

Interferon

TIBC -

Total Iron binding Capacity

Chronic liver disease

DCLD -

Decompensated chronic liver disease

Thrombopoietin

NAFLD -

Non Alcoholic Fatty Liver Disease

Non Alcoholic Steatohepatitis

Upper gastrointestinal

PCV -

Packed cell volume

MCV -

Mean Corpuscular volume

Mean Corpuscular hemoglobin

MCHC -

Mean Corpuscular hemoglobin concenteration

Chronic obstrutive pulmonary disease

CKD -

Chronic kidney disease

UrsoDeoxyCholic Acid

Ultrasonogram abdomen

OGD SCOPY - Oesophago Gatro Duodeno Scopy CTP Crieteria - CHILD TURCOT PUGH CRITERIA

TABLE OF CONTENTS

S. NO. CONTENT PAGE NO.

1 INTRODUCTION 1

2 AIMS AND OBJECTIVES 2

3 REVIEW OF LITERATURE 3

4 MATERIALS AND METHODS 37

5 OBSERVATIONS AND RESULTS 42

6 DISCUSSION 73

7 CONCLUSION 80

8 BIBLIOGRAPHY 81

9 ANNEXURES

I) PROFORMA II) CONSENT FORM III) MASTER CHART

87

89

91

LIST OF TABLES

S. NO. TABLE PAGE NO.

1 Age distribution among study population 42 2 Sex distribution among study population 43 3 Alcohol consumption among study population 44 4 Causes of DCLD among study population 45 5 Presenting symptoms among study population 47 6 Severity of Anaemia among study population 48 7 Peripheral Smear among study population 49 8 Mean Corpuscular Volume among study population 51

9 Alcoholic VS MCV 52

10 Platelet count among study population 53

11 UGI Bleed VS Platelet count 54

12 Splenomegaly among study population 55

13 WBC count among study population 56

14 Pancytopenia among study population 57

15 Alcoholic VS Pancytopenia 58

16 Prothrombin Time among study population 59

17 UGI bleed VS Prothrombin time 60

18 International Normalized Ratio among study

population 61

19 UGI bleed VS INR 62

20 Hepatic Encephalopathy among study population 63

21 Serum Protein levels among study population 64 22 Serum Albumin levels among study population 65 23 OGD Scopy findings among study population 66 24 Oesophageal Varices among study population 67 25 CHILD TURCOT PUGH CRITERIA among study

population 68

26 CTP grade VS Variceal bleed 69

27 OGD Scope findings VS Platelet count 70 28 OGD Scope findings VS Prothrobin time 71

29 OGD Scope findings VS INR 72

LIST OF CHARTS

S. NO. CHARTS PAGE NO.

1 Age distribution among study population 42 2 Sex distribution among study population 43 3 Alcohol consumption among study population 44 4 Causes of DCLD among study population 46 5 Presenting symptoms among study population 47 6 Severity of Anaemia among study population 48 7 Peripheral Smear among study population 50 8 Mean Corpuscular Volume among study population 51

9 Alcoholic VS MCV 52

10 Platelet count among study population 53

11 UGI Bleed VS Platelet count 54

12 Splenomegaly among study population 55

13 WBC count among study population 56

14 Pancytopenia among study population 57

15 Alcoholic VS Pancytopenia 58

16 Prothrombin Time among study population 59

17 UGI bleed VS Prothrombin time 60

18 International Normalized Ratio among study

population 61

19 UGI bleed VS INR 62

20 Hepatic Encephalopathy among study population 63

21 Serum Protein levels among study population 64

22 Serum Albumin levels among study population 65 23 OGD Scopy findings among study population 66 24 Oesophageal Varices among study population 67 25 CHILD TURCOT PUGH CRITERIA among study

population 68

26 CTP grade VS Variceal bleed 69

27 OGD Scope findings VS Platelet count 70 28 OGD Scope findings VS Prothrobin time 71

29 OGD Scope findings VS INR 72

1

INTRODUCTION

Liver plays an important role in homeostasis. Any disease affecting the functions of liver will cause a breach in whole body homeostasis. Liver plays a major role in carbohydrate metabolism, lipid metabolism and protein metabolism. Its role in endocrine and hematological manifestations are important. Loss of Liver function can manifest as subtle metabolic abnormalities and derangements in hematological parameters which can ultimately culminate in grave complications.

Liver plays a major role in maintaining the hematological parameters in normal and maintain the hemostasis. Liver is the storage site for iron, B12 and folic acid which are necessary for the normal hematopoiesis. Liver also secretes the clotting factors and the inhibitors and keep the hemostasis in equilibrium.

Hepatocellular failure, portal hypertension and jaundice may affect the blood picture. Chronic Liver disease is usually accompanied by hypersplenism. Diminished erythrocyte survival is frequent. In addition both parenchymal hepatic disease and cholestatic jaundice may produce blood coagulation defects. Dietary deficiencies, alcoholism, bleeding and difficulties in hepatic synthesis of proteins used in blood formation or coagulation add to complexity of the problem.

Spontaneous bleeding, bruising and purpura together with a history of bleeding after minimal trauma such as venepuncture, are most important indications of a bleeding tendency in patients with liver disease than lab tests.

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AIM OF THE STUDY

To assess the hematological profile of patients with decompensated chronic liver disease

OBJECTIVES OF THE STUDY:

• 1.To assess the prevalence of anaemia in patients with decompensated chronic liver disease

• 2.To find the type of anaemia in a patient with decompensated chronic liver disease

• 3.To assess the prevalence of thrombocytopenia in patients with decompensated chronic liver disease with GI bleeding

• 4.To assess the coagulation profile in patients with decompensated chronic liver disease with GI bleeding

• 5.To assess the prevalence of pancytopenia in patients with decompensated chronic liver disease

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REVIEW OF LITERATURE

LIVER STRUCTURE AND FUNCTION

The liver is the largest organ of the body, weighing about 1-1.5 kg and representing 1.5-2.5% of the lean body mass. The size and shape of the liver vary according to the general body shape - long and lean or squat and square. Liver is located in the right upper quadrant of the abdomen under the right lower rib cage against the diaphragm. It is held in place by the ligamentous attachments to the diaphragm, peritoneum, great vessels, and upper gastrointestinal organs. The liver receives a dual blood supply; ~20% of the blood flow is from hepatic artery, and 80% is from the portal vein.

The majority of cells in the liver are hepatocytes, which constiutes 2/3^rd of the organ‟s mass. The remaining cell types are kupffer cells, stellate cells, endothelial cells and bile ductular cells. Hepatocytes are involved in synthesis of albumin, coagulation factors, carrier proteins, production of bile and its carriers, regulation of nutrients and the metabolism and conjugation of lipophilic compounds for excretion in bile or urine.

Functions of liver

1. Formation and secretion of bile 2. Storage function

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Glycogen storage Lipid storage

B12 and Folic acid storage Fat and water soluble vitamins 3. Inactivation of various substances

Toxins Steroids Hormones

4. Secretion of plasma proteins Albumin

Fibrinogen a1-antitrypsin Ceruloplasmin Haptoglobins Transferrin

C3 component of complement 5. Synthesis of Immuno globulins,

IgG, IgM, IgA 6. Synthesis of Urea

5

CIRRHOSIS

Cirrhosis is defined anatomically as a diffuse process with fibrosis and nodule formation. It is the end result of the fibrogenesis that occurs with chronic liver injury.

According to functional status of liver, cirrhosis may be compensated cirrhosis or decompensated cirrhosis.

Compensated cirrhosis

The disease may be discovered at a routine examinationor biochemical screen, or at operation undertaken forsome other condition.

Cirrhosis may be suspected if thepatient has vascular spiders, palmar erythema, unexplainedepistaxis or oedema of the ankles. Firm enlargementof the liver, particularly in the epigastrium, andsplenomegaly are helpful diagnostic signs. Confirmationshould be sought by biochemical tests, scanning and, ifnecessary, liver biopsy.

Biochemical tests may be quite normal in this group.The most frequent changes are a slight increase in theserum transaminase or γ - glutamyl transpeptidase concentration.

Portal hypertension may be present evenwith normal liver function tests. Diagnosis is confirmedby liver imaging or needle liver biopsy .These patients may remain compensated until theydie from another cause. Hepatocellular carcinomaoccurs at a rate of 1–3% per year and appropriatescreening is recommended

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Decompensationmay be precipitated by bacterial infection,surgery, trauma or medication.

Decompensated cirrhosis

Cirrhosis is said to be decompensated , when it presents with any of complications.

1. Variceal haemorrhage 2. Ascites

3. Hepatic encephalopathy 4. Jaundice

The patient usually seeks medical advice because of ascites, jaundice or gastrointestinal bleeding. General health fails with weakness, muscle wasting and weight loss. Continuous mild fever (37.5 – 38 ° C) is often due to Gram - negative bacteraemia, to continuing hepatic cell necrosis, ongoing alcoholic hepatitis or to a complicating hepatocellular carcinoma. A liver flap may be present. Cirrhosis is the commonest cause of hepatic encephalopathy.

Jaundice implies that liver cell destruction exceeds the capacity for regeneration and is always serious. The deeper the jaundice the greater the inadequacy of liver cell function.

The skin may be pigmented. Clubbing of the fingers is occasionally seen. Purpura over the arms, shoulders and shins may be associated with

7

a low platelet count.The circulation is over - active. The blood pressure is low.

Sparse body hair, vascular spiders, palmar erythema, white nails and gonadal atrophy are common.

Ascites is usually preceded by abdominal distension.Oedema of the legs is frequently associated. The liver may be enlarged, with a firm regular edge,or contracted and impalpable. The spleen may be palpable.

CIRRHOSIS - CAUSES 1. Alcohol

2. Infections

Viral hepatitis B, C, D Schistosomiasis

Toxoplasmosis Congenital syphilis 3. Autoimmune diseases

Autoimmune hepatitis Autoimmune cholangitis Primary biliary cholangitis Primary sclerosing cholangitis Wegener‟s granulomatosis 4. Drugs

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Amiodarone, Methotrexate Dantrolene, Methyldopa Halothane, Nitrofurantoin Isoniazid, Propylthiouracil MAO inhibitors

5. Chemical agents

Arsenic, Phosphorus, Carbon tetrachloride, Copper Trichloroethylene,

Mycotoxins

6. Cholestatic diseases Chronic cholangitis

Caroli‟s syndrome Bile-duct atresia

Choledochal cyst Bile-duct stenoses 7. Venous congestion

Budd-Chiari syndrome Constrictive pericarditis Right-sided heart failure Veno-occlusive disease

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8. Metabolic diseases

Non-alcoholic steatohepatitis Wilson‟s disease

Haemochromatosis Gaucher‟s disease Thalassaemia

α1-antitrypsin deficiency Abetalipoproteinaemia Acute intermittent porphyria Erythrohepatic protoporphyria Porphyria cutanea tarda

Fructose intolerance Galactosaemia Hurler‟s disease Hypermethioninaemia Mucoviscidosis

Neonatal adrenoleucodystrophia Nieman-Pick disease

Wolman‟s disease

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Zellweger syndrome 9. Rendu-Osler-Weber disease 10. Indian childhood cirrhosis 11. Cryptogenic cirrhosis (<10%)

Clinical features of cirrhosis

1. Weakness, muscle wasting and weigh loss 2. Low grade fever

3. Jaundice

4. Skin pigmentation 5. Ascites, Edema of legs

6. Purpura/spontaneous bruising 7. Loss of libido gonadal atrophy 8. Sparse body hair

9. White nails palmar erythema 10. Vascular spiders

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Portal hypertension

A) In liver cirrhosis, portal hypertension is caused by increased intrahepatic resistance to the passage of blood flow caused by liver fibrosis and regenarative nodules.

B) Increased splanchnic blood flow secondary to vasodilatation within the splanchnic vascular bed.

C) In patients with liver cirrhosis, development of portal hypertension is accompanied by splenomegaly, hypersplenism resulting in thrombocytopenia, development of ascites, encephalopathy and esophageal varices.

D) HVPG > or = 10 mmHg is taken as a evidence of portal hypertension. Hepatic venous pressure gradient (HVPG) is the difference between the wedged(WHVP) and the free hepatic venous pressures(FHVP).

E) Portal hypertension leads to formation of porto-caval anastamoses, resulting in esophageal varices , caput medusae and internal haemorrhoids.

F) Sites of porto-caval anastamoses:

Lower esophagus - left gastric veins with azygos veins

Upper anal canal - superior rectal vein with middle/inferior rectal veins

12

Paraumblical - Caput medusae

Bare area of Liver - Hepatic / Portal vein with inferior phrenic veins

Retro peritoneal - colonic veins with veins of posterior abdominal wall

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Signs of Hepato cellular failure Face

Parotid enlargement Loss of eye brows Xanthelasma Telengectasia Paper money skin

Hands Pallor White nails

Duputyren's contracture Palmar erythema

Clubbing Skin

Spider nevi Scanty body hair Scratch marks Nutrition

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Muscle wasting

Glossitis&Angular stomatitis Endocrine

Gynaecomastia Testicular atrophy

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Features due to portal hypertension Splenomegaly

Ascites

Esophageal varices Anorectal varices

Dilated veins over abdomen

COMPLICATIONS OF CIRRHOSIS Bleeding oesophageal varices

A serious consequence of portal hypertension is the formation of collateral circulatory systems with characteristic haemodynamic circulation. Enhanced inflow of blood from the splanchnic area into the portal vein or decreased resistance in the arterial splanchnic circulation increases portal hypertension.

Oesophageal varices, like cardia varices and fundus varices, arise from a regional stasis of submucosal perioesophageal and paraoesophageal veins. These varices are supplied by the left gastric vein and posterior gastric vein, while stomach varices are additionally served by the branches of the splenic vein and short gastric veins.

Fundus varices may also receive a direct supply via a-v shunts in the stomach wall.

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Some 60-80% of all patients with portal hypertension develop oesophageal varices at some stage of their lives, half of them within two years and up to 90% within ten years of the initial diagnosis.

In 90-95% of cases, the varices are localized in the middle and lower third of the oesophagus (“junction zone”, i.e. in the area 2-6 cm above the oesophagogastric junction), and in 5-10% of cases, they are found in the area of the stomach fundus. Approximately 15% of patients have both oesophageal

and stomach varices.

About 30-50% of oesophageal varix patients suffer from variceal bleeding during the course of their lives. The risk of initial haemorrhage in a group of untreated cirrhosis patients is 20% per year (about 30%

within three years).

Primary oesophageal bleeding proves fatal in 30-40% of cases despite adequate conservative treatment or emergency intervention.

Some 20-25% of all cirrhosis patients die as a direct result of bleeding oesophageal varices.

The lethality rate for each haemorrhage episode varies among the Child groups (A-10%, B-30 to40%, C > 70%).

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HEPATIC ENCEPHALOPATHY

Hepatic encephalopathy is the commonest complication of cirrhosis;

it has a detrimental effect on health - related quality of life and on survival.

Ammonia plays a key role in the pathogenesis of the syndrome via the induction of astrocyte swelling and the development of low-grade cerebral oedema; oxidative stress, disrupted glial–neuronal communication and

neuronal dysfunction follow.

Classification

1. Minimal hepatic encephalopathy 2. Overt hepatic encephalopathy

i. Episodic overt hepatic encephalopathy ii. Persistent overt hepatic encephalopathy

Precipitants of hepatic encephalopathy in patients with cirrhosis Gastrointestinal bleeding

Sepsis

Electrolyte imbalance Hyponatraemia, Hypokalaemia

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Dehydration

Fluid restriction , Excessive diuresis Paracentesis

Diarrhoea/ vomiting Constipation

Excess protein load Alcohol misuse CNS - active drugs

TIPS (transjugular intrahepatic portal–systemic shunt) insertion

West Haven Criteria for grading mental state in patients with cirrhosis Grade 0 --No abnormalities detected

Grade I --Trivial lack of awareness, Euphoria or anxiety, Shortened attention span, Impairment of addition or subtraction

Grade II --Lethargy or apathy, Disorientation for time, Obvious personality change, Inappropriate behaviour

Grade III-- Somnolence to semi-stupor, Responsive to stimuli, Confused

Gross disorientation, Bizarre behaviour Grade IV-- Coma, unable to test mental state

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There is no diagnostic gold standard; a combination of clinical examination, psychometric testing and electroencephalography is recommended.

Therapy is directed at reducing circulating ammonia by use of non- absorbable disaccharides and non-absorbable antibiotics.

GRADING OF CIRRHOSIS

Severity of cirrhosis is assessed by various grading systems.

Important among those are

1. Child pugh (child turgott pugh- CTP) grading

2. MELD (Model for End stage Liver Disease) grading

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As we can see from the above picture, the parameters used to calculate CTP grading, comprises Serum Bilirubin levels, Serum Albumin levels and Prothrombin time and INR.

Ascites and presence of hepatic encephalopathy are also taken into account while calculating CTP grading.

The above grading is used to determine the prognostic significance of a particular patient.

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HAEMATOLOGICAL DISORDERS OF THE LIVER DISEASE Chronic liver failure is usually associated with hypersplenism and diminished erythrocyte survival is frequent. Dietary deficiencies, alcoholism, bleeding and defective hepatic synthesis of proteins used in blood formation or coagulation worsen the problem.

BLOOD VOLUME

Plasma volume is increased in patients with cirrhosis, particularly in those with ascites. This hypervolaemia may account for a low peripheral hemoglobin or erythrocyte level. Total circulating hemoglobin is reduced in only half the patients.

ANAEMIA IN CIRRHOSIS Anaemia in cirrhosis is due to

i. Hemodilution - due to increased plasma volume.

ii. Shortened red cell survival - hypersplenism

iii. Reduced bone marrow response to anaemia due to reduced erythropoietin level,

iv. Chronic inflammation and increased level of inflammatory cytokines suppressing the bone marrow

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ERYTHROCYTE CHANGES

Red cells may be hypochromic. This is due to gastrointestinal bleeding, leading to iron deficiency. In portal hypertension, anaemia follows gastro-oesophageal bleeding and is increased by thrombocytopenia and disturbed blood coagulation. Epistaxis, bruising and bleeding gums add to the anaemia.

The erythrocytes are usually normocytic . This is a combination of the microcytosis of chronic blood loss and the macrocytosis inherent in patients with liver disease. Thus the red cell membrane cholesterol and phospholipid content and ratio is changed and this results in various morphological abnormalities, including thin macrocytes and target cells.

23

Alcoholics show genuine thick macrocytes, which are related to the toxic effect of alcohol on the bone marrow. Folic acid and vitamin B12 deficiency also contribute to macrocytosis.

Spur cells are cells with unusual, thorny projections.They are also termed acanthocytes. They are associated with advanced liver disease, usually in alcoholics. Severe anaemia and haemolysis are also found.

Their appearance is a bad prognostic sign.

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Scanning electron micrograph of abnormal red cells from a patient with alcoholic hepatitis, showing echinocytes (E) at various stages of development, and an acanthocyte (A).

Bone marrow of chronic hepatocellular failure is hyperplastic and normoblastic. Inspite of this, erythrocyte volume is depressed and the marrow therefore does not seem to compensate completely for the anaemia (relative marrow failure).

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Stages of Hematopoiesis

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Iron metabolism

Low or normal serum iron concentration with a low or normal total iron binding capacity is frequently found in uncomplicated cirrhosis. In alcohol induced liver disease,alcohol has toxic effect and suppresses the bone marrow but it increases the iron absorption from the GIT. Hepatic inflammation and necrosis tend to increase serum ferritin.

The rise in MCV which accompanies CLD and alcohol ingestion masks the iron deficiency. Serum iron is bound to Beta globulin transferrin which is synthesized in liver, total iron binding capacity largely depends on the transferrin concentration. High total iron binding capacity indicates iron deficiency. TIBC is often lowered the patients with CLD due to decreased synthesis of transferrin. Serum transferrin receptor level is a more reliable lab index of iron deficiency in patients with liver disease.

Iron deficiency also associated with hemorrhage and hemolysis.

Iron deficiency causes microcytic hypochromic anaemia.

Folate and vitamin B12 metabolism

The liver stores folate and converts it to its active storage form, tetrahydrofolate. Folate deficiency occurs in chronic liver disease, usually in the alcoholic. This is largely due to dietary deficiency. Serum folate levels are low. Folate therapy is useful. The liver also stores

27

vitamin B12. Hepatic levels are reduced in liver disease. When hepatocytes become necrotic vitamin B12 is released into the blood and high serum B12 levels are recorded.

Erythrocyte survival and haemolytic anaemia

Increased red cell destruction is almost constant in hepatocellular failure and jaundice of all types. This is reflected in erythrocyte polychromasia and reticulocytosis.The mechanism is extremely complex.The major factor is hypersplenism with destruction of red blood cells in the spleen. Also, spur cells have membrane defects, particularly decreased fluidity, and this, with the altered architecture, exacerbates splenic destruction.

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Haemolysis may occur in Wilson‟s disease and this diagnosis is likely in a young patient presenting with haemolysis and liver dysfunction.

Haemolysis may be acute in patients with alcoholic hepatitis who also have hypercholesterolaemia ( Zieve‟s syndrome ) .

29

Rarely, an autoimmune haemolytic anaemia with a positive Coomb‟s test is seen in chronic hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis.

Aplastic anaemia is a rare complication of acute viral hepatitis, usually type non - A to E hepatitis.

Changes in the leucocytes

Leucopenia and thrombocytopenia are commonly found in patients with cirrhosis, usually with a mild anaemia ( „ hypersplenism ‟ ).

Leucocytes

Leucopenia in the range of 1.5 – 3.0 × 10^9 /L, with the depression mainly affecting polymorphs. In neutrophil function , there is a disturbance in late maturation compartment of granulocyte differentiation. Hence , Chemotaxis is inhibited.

Causes for leucopenia in CLDs

1. Portal hypertension-induced splenic and splanchnic sequestration

2. Alterations in granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor

3. Bone marrow suppression mediated by toxins (eg, alcohol, hepatitis B and C)

30

Leucocytosis accompanies spontaneous bacterial peritonitis, cholangitis, fulminant hepatitis, alcoholic hepatitis, hepatic abscess and malignant disease.

Changes in Platelets

Multiple factors can cause or contribute to the development of thrombocytopenia in patients with chronic liver disease. These include

1. Portal hypertension with resulting hypersplenism, 2. Hepatocellular carcinoma and chemotherapy, 3. Anti-platelet antibodies,

4. Decreased levels or activity of the platelet growth factor thrombopoietin,

5. Bone marrow suppression of thrombopoiesis due to antiviral therapy (e.g., IFN) and/or

6. Direct myelosuppressive effects of HCV infection

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In patients with chronic liver disease and portal hypertension, a low platelet count is due to splenic sequestration and low thrombopoietin levels. Plasma concentration of thrombopoietin, the key regulator of platelet function produced mainly by the liver, is reduced in patients with cirrhosis.Decreased production of platelets from the bone marrow may also be due to alcohol excess, folic acid deficiency and viral hepatitis.

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VARIOUS MECHANISMS OF THROMBOCYTOPENIA

Thrombocytopenia in chronic liver disease (usually 60 – 90 × 10⁹ /L) is frequent and is largely due to hypersplenism. The circulating platelets and leucocytes, although in less in number, are functioning well, in contrast to those of leukaemia.

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LIVER AND BLOOD COAGULATION

Impaired blood coagulation in patients with hepatobiliary disease is a complex process. This is due to the changes in pathways that lead to fibrin production occurring at the same time as changes in the fibrinolytic process. However, there is little relationship between abnormal clotting tests and risk of bleeding. Platelet number and function may be more important than the degree of abnormality of the prothrombin time for risk of bleeding with invasive procedures.

The hepatocyte is the principal site of synthesis of all the coagulation factors including vitamin K - dependent factors II, VII, IX and X,

labile factor V, factor VIII, factors XI and XII, fibrinogen and fibrin- stabilizing factor XIII.

Coagulopathies, defined as defects in clotting, are commonly observed in patients with decompensated cirrhosis and acute liver failure. Coagulopathy often results from liver damage and/or loss of liver synthetic function,

leading to diminished capacity to produce clotting factors (e.g., factors I (fibrinogen), II (prothrombin), V,VII, IX, X, XI, protein C, and antithrombin) and increased bleeding risk. Platelets have a dual role in hemostasis. During primary hemostasis, platelets adhere to the subendothelium at the site of liver injury through the adhesive protein

34

von Willebrand factor (vWF) and then platelets aggregate with each other through vWF and fibrinogen, producing the platelet plug. Recent observations suggest that patients with chronic liver disease have elevated levels of vWF and that increased vWF may at least partially compensate for decreased numbers of platelets and its reduced functional capacity.

During secondary hemostasis (coagulation), platelets expose on their surface negatively charged phospholipids that act as receptors for the plasmatic coagulation factors, thus triggering thrombin generation, fibrin formation and platelet plug stabilization.

35

COAGULATION CASCADE

Alcohol can interfere with these processes at several levels.

Hepatic injury caused by alcohol could cause diminished synthesis of the clotting factors. Prothrombin time represents the activity of extrinsic pathway of coagulation assessing the activity of coagulation factors I (fibrinogen), II (prothrombin), V, VII and IX.

36

CHRONIC LIVER DISEASE AND PANCYTOPENIA

Pancytopenia associated with alcoholic liver disease is due to hyper- splenism, megaloblastic anaemia and primary bone marrow suppression.

The main feature of this syndrome is injury to or loss of pluripotent hematopoietic stem cells, in the absence of infiltrative disease of the bone marrow.

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DESIGN OF STUDY MATERIALS AND METHODS:

This will be a Cross sectional analytical study done in – Department of General medicine, Coimbatore Medical College Hospital, Coimbatore. This study includes 100 cases of decompensated chronic liver disease. All patients taken up for the study are evaluated in detail. Oral consent was obtained for clinical examination and lab investigations. Written consent was obtained for procedures such as upper GI endoscopy. All the tests are done with the permission from the Institutional Ethical Committee and informed consent from the subjects.

DESIGN OF STUDY: Cross sectional analytical study.

PERIOD OF STUDY: One year.

STUDY PROTOCOL:

This is a Cross sectional analytical study to assess the hematological abnormalities in 100 cases of Decompensated Chronic Liver Disease Patients. Once thepatients were confirmed as a case of decompensatedchronic liver disease then, they were said toundergo tests such as complete hemogram, liver function tests, peripheral smear study, PT, aPTT, INR & viralmarkers.Informed/written consent will be obtained from each patient. UGI scopy and ultrasoundabdomen were done for all the patients.A detailed history was taken such as abdominal

38

pain,abdominal distension, decreased urine output,yellowish discolouration of urine and eyes, loss ofappetite, loss of weight, early satiety and fever.

To assess RBC abnormality 1. RBC count:

Done using auto analyser.

Normal value : 4.5 to 6 million per mm3 2. Hemoglobin estimation:

Done by Sahli's method or auto analyser.

Normal value : Male 14 to 18 Gm%, Female 12 to 16 Gm%.

3. Packed cell volume (PCV) Estimated by autoanalyser

Normal value : Male 42 to 52%. Female: 37 to 47 % 4. MCV, MCHC, MCH:

- are estimated by auto analyser MCV - 80 to 97 fl

MCH - 26 to 33 pg/dl MCHC - 32-35 gm/dl

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5. Peripheral smear for blood picture

Using stains, blood picture is examined with a lab microscope.

Low power field examination:

- Quality of film

- Number, distribution and staining of WBCs - RBCs examination

High power field examination:

Assess RBC - Size,Shape 6. Reticulocyte count:

Stain - 1% brilliant cresyl blue Normal - 0.2-2%

To assess WBC abnormality:

1. Total WBC count Estimated by autoanalyser

Normal 3,800-9,000 cells per mm3 2. Differential count

Assessed by direct staining and visualizing with microscope.

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To Assess hemostasis 1. Platelet count

Using auto analyser.

Normal : 1.5 - 4.5 lakhs

2. Prothrombin time: Normal 10-14 sec.

3. Activated partial thromboplastin time: Normal 24-34 sec.

Assessing Spleen size using ultrasonogram:

Mild splenomegaly : 1-3 cm enlargement Moderate splenomegaly : 4-8 cm enlargement

Severe splenomegaly : > 8 cm enlargement Upper GI endoscopy

UGI endoscopy was done at MGE department. After explaning about the procedure and its side effects, written consent was obtained from the patient. Results were collected and co-related to establish the diagnosis.

41

INCLUSION CRITERIA:

1.All patients with liver disease whose symptoms persists for more than 6 months

2.Alcoholic cirrhosis, Post-infective & metabolic causes of chronic liver diseases are taken in consideration

EXCLUSION CRITERIA:

1. Patients with known primary hepatocellular carcinoma or GI malignancies were excluded.

2.Patients with primary coagulation disorders or primary abnormalities in hemostatic function were excluded.

3.Patients with pre-existing anaemia of other causes were excluded.

4.Patients with Acute hepatic failure were excluded.

5.Patients suffering from end stage medical diseases like CKD, Coronary artery disease, Cardiac failure, COPD were excluded

6. Consent not given.

42

OBSERVATION AND RESULTS

This study regarding assessment of hematological profile among100 inpatients of decompensated liver disease was conductedin coimbatore medical college hospital.

Out of 100 patients in this study, there are 86 male patients and 14 femalepatients. Theage of patients in this study were in the range from 20 to 60.

Table 1. AGE DISTRIBUTION OF THE SYUDY POPULATION AGE IN YEARS NO OF PATIENTS PERCENTAGE

<30 4 4%

31-40 23 23%

41-50 34 34%

51-60 29 29%

> 60 10 10%

Chart 1. AGE DISTRIBUTION OF THE SYUDY POPULATION

4%

23%

34%

29%

10%

<30 31-40 41-50 51-60 > 60

43

Table 2.SEX DISTRIBUTION OF THE STUDY POPULATION

SEX NO OF PATIENTS PERCENTAGE

MALE 86 86%

FEMALE 14 14%

Chart 2.SEX DISTRIBUTION OF THE STUDY POPULATION

86

14

MALE FEMALE

44

Table 3. ALCOHOL CONSUMPTION AMONG STUDY POPULATION

ALCOHOLIC NO OF PATIENTS PERCENTAGE

YES 67 67%

NO 33 33%

Among 86 male patients, 59 gave history of alcoholism and among the 14femalepatients,8 patients were found to be alcoholic.

Chart 3. ALCOHOL CONSUMPTION AMONG STUDY POPULATION

67

33

YES NO

45

Table 4. CAUSES OF DCLD AMONG STUDY POPULATION

CAUSE

ALCOHOL 67

VIRAL INFECTION 13

AUTOIMMUNE 3

WILSON 3

NASH 8

CRYPTOGENIC 7

BILIARY CIRRHOSIS 2

Most of the patients in the study were in the middle age group and only 4% were inyounger age. Out of four patients two patients were diagnosed to have Wilson's disease. Remaining 96 patients were diagnosed as chronicdecompensated liver diseaseof variable etiology.

Among the variable etiologies, alcoholic CLDs include around 67% , followed by Cirrhosis of viral etiology comprising of 13%, NASH -induced cirrhosis - 8%, cryptogenic cirrhosis - 7%. Other minor causes are biliary cirrhosis, wilson‟s disease and autoimmune hepatitis induced cirrhosis.

46

Chart 4. CAUSES OF DCLD AMONG STUDY POPULATION

As we can see from the above graph, alcohol induced liver injury being the most common cause of cirrhosis in the study population, we clearly enquired about the amount of alcohol consumption, years of consumption, type of alcohol consumed, history of binge drinking and other variables relating to alcohol consumption to establish the causative co-relation of alcohol consumption with the development of cirrhosis.

67

13

3 3 8 7

2

47

Table 5. PRESENTING SYMPTOMS AMONG STUDY POPULATION

SYMPTOMS PRESENT

ABD DISTENSION 100

JAUNDICE 39

FEVER 26

UGI BLEED 54

Chart 5. PRESENTING SYMPTOMS AMONG STUDY POPULATION

100

39

26

54

ABD DISTENSION JAUNDICE FEVER UGI BLEED

48

ANALYSIS OF RBCS

Patients in the study were analysed for the presence of anaemia and thecharacteristics of anaemia when present.

Ninety one patients had anaemia and only nine patients had normal hemoglobinabove 12 gm%. About 29 patients had severe anaemia less than 8 gm%.

Table 6. SEVERITY OF ANEMIA AMONG STUDY POPULATION

SEVERITY OF ANEMIA NO OF PATIENTS PERCENTAGE

> 12 (NORMAL) 9 9%

10-12 (MILD) 19 19%

8-10 (MODERATE) 53 53%

< 8 (SEVERE) 29 29%

Chart 6. SEVERITY OF ANEMIA AMONG STUDY POPULATION

8%

17%

48%

27%

> 12 10-12 (MILD) 8-10 (MODERATE) < 8 (SEVERE)

49

CHARACTERISTICS OF ANAEMIA

All the nine patients with normal hemoglobin level had normochromic andnormocytic blood picture.

Among the 91 patients, who had anaemia,41 patients had normochromic andnormocytic anaemia, 23 patients had macrocytic anaemia, 14 patients had microcytic hypochromic picture and

14 patients had dimorphic anaemia. Five patients with microcytic anaemia showed anisocytosisand poikilocytosis. Target cells were seen in only bthree patients. Acanthocytes were seen in peripheral picture of 6 patients.

Table 7. PERIPHERAL SMEAR AMONG STUDY POPULATION

PERIPHERAL SMEAR NO OF PATIENTS PERCENTAGE

NORMAL 8 8%

NORMOCHROMIC NORMOCYTIC

41 41%

MACROCYTIC 23 23%

MICROCYTIC HYPOCHROMIC

14 14%

DIMORPHIC 14 14%

50

Chart 7. PERIPHERAL SMEAR AMONG STUDY POPULATION

8

41

23

14 14

NORMAL NORMOCHROMIC NORMOCYTIC

MACROCYTIC MICROCYTIC HYPOCHROMIC

DIMORPHIC

51

Table 8. MEAN CORPUSCULAR VOLUME AMONG STUDY POPULATION

MCV NO OF PATIENTS PERCENTAGE

< 80 18 18%

80-100 59 59%

> 100 23 23%

Chart 8. MEAN CORPUSCULAR VOLUME AMONG STUDY POPULATION

18

59

23

< 80 80-100 > 100

52

Table 9. ALCOHOLIC VS MCV

ALCOHOLIC

MCV

MEAN SD

YES 93.96 14.47

NO 82.5 14.51

P VALUE - 0.012 UNPAIRED T TEST

SIGNIFICANT

Chart 9. ALCOHOLIC VS MCV

93.96

82.5

YES NO

53

PLATELET ABNORMALITIES

Among 100 patients in this study, Thrombocytopenia was found to be in 80 patients. Severe thrombocytopenia of <50,000 cells/mm³ was found to be in 22 patients. Among the patients with atleast one episode of UGI bleed, the mean platelet count was about 66.46 * 10³ . And the mean platelet count was around 152.42* 10³ , in those who never had a bleeding episode. This shows a statistical linear co-relation between platelet count and episodes of UGI bleed.

Table 10. PLATELET COUNT AMONG STUDY POPULATION

PLATELET COUNT NO OF PATIENTS PERCENTAGE

< 50000 22 4%

50,000 - 1 LAKH 36 23%

1-1.5 LAKH 22 34%

1.5-2 LAKH 8 29%

> 2 LAKH 12 10%

Chart 10. PLATELET COUNT AMONG STUDY POPULATION

22%

36%

22%

8%

12%

< 50000 50,000 - 1 LAKH 1-1.5 LAKH 1.5-2 LAKH > 2 LAKH

54

Table 11. UGI BLEED VS PLATELET COUNT

UGI BLEED

PLATELET COUNT

MEAN SD

PRESENT 66.46 21.32

ABSENT 152.42 51.62

P VALUE - 0.001 UNPAIRED T TEST

SIGNIFICANT

Among the patients with atleast one episode of UGI bleed, the mean platelet count was about 66.46 * 10³ . And the mean platelet count was around 152.42* 10³ , in those who never had a bleeding episode.

This shows a statistical linear co-relation between platelet count and episodes of UGI bleed.

Chart 11. UGI BLEED VS PLATELET COUNT

66.46

152.42

PRESENT ABSENT

55

Table 12. SPLENOMEGALY AMONG STUDY POPULATION

SPLENOMEGALY NO OF PATIENTS PERCENTAGE

ABSENT 20 20%

MILD 38 38%

MODERATE 24 24%

SEVERE 18 18%

Among the patients with severe thrombocytopenia (platelet count <

50,000), about 12 patients had severe splenomegaly and 8 patients had moderate splenomegaly.

Chart 12. SPLENOMEGALY AMONG STUDY POPULATION

20%

38%

24%

18%

ABSENT MILD MODERATE SEVERE

56

WBC ABNORMALITIES

The analysis of WBCs were done with the total count and the differential count. Thetotal count of WBCs range from 1300/mm³ to 18,200/mm³. Among the 100 patients,17 patients hadleucocytosis, of which 6 patients had lymphocytosis. Leucocytosis were observed in patients with feverdue to secondary infection of ascites due to repeated paracentesis and due to spontaneous bacterial peritonitis. Leucopenia is present in 19% of patients.

Table 13. WBC COUNT AMONG STUDY POPULATION

WBC COUNT NO OF PATIENTS PERCENTAGE

< 3000 19 19%

3000-6000 47 47%

6000-9000 17 17%

9000-12000 6 6%

> 12000 11 11%

Chart 13. WBC COUNT AMONG STUDY POPULATION

19%

47%

17%

6%

11%

< 3000 3000-6000 6000-9000 9000-12000 > 12000

57

Table 14. PANCYTOPENIA AMONG STUDY POPULATION

PANCYTOPENIA NO OF PATIENTS PERCENTAGE

PRESENT 35 35%

ABSENT 65 65%

Chart 14. PANCYTOPENIA AMONG STUDY POPULATION

35

65

PRESENT ABSENT

58

Table 15. ALCOHOLIC VS PANCYTOPENIA

ALCOHOLIC

PANCYTOPENIA

PRESENT ABSENT

YES 33 34

NO 2 31

P VALUE - 0.001 CHI SQUARE TEST

SIGNIFICANT

Chart 15. ALCOHOLIC VS PANCYTOPENIA

33 34

2

31

PRESENT ABSENT

PANCYTOPENIA YES NO

59

PROTHROMBIN TIME

The liver secretes all the clotting factor except factor VIII and VWF.

As we have nofacility for estimation of individual clotting factors, the patients was assessed for thecoagulation profile by testing for prothrombin time and INR.

Table 16. PROTHROMBIN TIME AMONG STUDY POPULATION

PROTHROMBIN TIME NO OF PATIENTS PERCENTAGE

14-18.2 SEC 16 16%

18.2-20.2 SEC 13 13%

> 20.2 SEC 71 71%

Chart 16. PROTHROMBIN TIME AMONG STUDY POPULATION

16%

13%

71%

14-18.2 SEC 18.2-20.2 SEC > 20.2 SEC

60

Table 17. UGI BLEED VS PROTHROMBIN TIME

UGI BLEED

PROTHROMBIN TIME

MEAN SD

PRESENT 24.25 8.12

ABSENT 21.05 3.85

P VALUE - 0.013 UNPAIRED T TEST

SIGNIFICANT

Chart 17. UGI BLEED VS PROTHROMBIN TIME

24.25

21.05

PRESENT ABSENT

61

Table 18. INTERNATIONAL NORMALISED RATIO AMONG STUDY POPULATION

INR NO OF PATIENTS PERCENTAGE

< 1.7 63 63%

1.7-2.3 34 34%

> 2.3 3 3%

Chart 18. INTERNATIONAL NORMALISED RATIO AMONG STUDY POPULATION

63%

34%

3%

< 1.7 1.7-2.3 > 2.3

62

Table 19. UGI BLEED VS INR

UGI BLEED

INR

MEAN SD

PRESENT 1.73 0.27

ABSENT 1.5 0.31

P VALUE - 0.03 UNPAIRED T TEST

SIGNIFICANT

Chart 19. UGI BLEED VS INR

1.73

1.5

PRESENT ABSENT

63

Table 20. HEPATIC ENCHEPHALOPATHY AMONG STUDY POPULATION

HEPATIC ENCEPHALOPATHY NO OF PATIENTS PERCENTAGE

NONE 72 72%

MINIMAL 14 14%

PROFOUND 14 14%

Chart 20. HEPATIC ENCHEPHALOPATHY AMONG STUDY POPULATION

72

14 14

NONE MINIMAL PROFOUND

64

SERUM PROTEIN LEVELS

Patients were analysed for the estimation of serum proteins, which is the syntheticfunction of the liver and evaluated for albumin globulin ratio which will be altered in thechronic liver disease patients.

Table 21. SERUM PROTEIN LEVELS AMONG STUDY POPULATION

SERUM PROTEIN NO OF PATIENTS PERCENTAGE

> 6.8 27 27%

5 - 6.8 70 70%

< 5 3 3%

Chart 21. SERUM PROTEIN LEVELS AMONG STUDY POPULATION

27

70

3

> 6.8 5 - 6.8 < 5

65

SERUM ALBUMIN LEVELS

Among 100 patients only 27% had total proteins more than 6.8 gm%

and only three patients had total protein <5 gm% and others in the middle group. All the 100 patients had albumin globulin ratio reversal, which is again towards the diagnosis of CLD.

Table 22. SERUM ALBUMIN LEVELS AMONG STUDY POPULATION

SERUM ALBUMIN NO OF PATIENTS PERCENTAGE

> 3.5 5 5%

3-3.5 24 24%

< 3 71 71%

Chart 22. SERUM ALBUMIN LEVELS AMONG STUDY POPULATION

5%

24%

71%

> 3.5 3-3.5 < 3

66

Table 23. OGD SCOPY FINDINGS AMONG STUDY POPULATION

OGD SCOPY NO OF PATIENTS PERCENTAGE

NORMAL 29 29%

GRADE I VARICES 22 22%

GRADE II VARICES 24 24%

GRADE III VARICES 25 25%

Chart 23. OGD SCOPY FINDINGS AMONG STUDY POPULATION

29%

24% 22%

25%

NORMAL GRADE I VARICES GRADE II VARICES GRADE III VARICES

67

Table 24. OESOPHAGEAL VARICES AMONG STUDY POPULATION

VARICES NO OF PATIENTS PERCENTAGE

PRESENT 71 71%

ABSENT 29 29%

Chart 24. OESOPHAGEAL VARICES AMONG STUDY POPULATION

71

29

PRESENT ABSENT

68

Table 25. CHILD TURCOT PUGH CRITERIA AMONG STUDY POPULATION

CTP GRADING NO OF PATIENTS PERCENTAGE

GRADE B 54 54%

GRADE C 46 46%

Chart 25. CHILD TURCOT PUGH CRITERIA AMONG STUDY POPULATION

54%

46%

GRADE B GRADE C

69

Table 26. CTP GRADE VS VARICEAL BLEED

CTP GRADE

VARICEAL BLEED

PRESENT ABSENT

GRADE B 29 25

GRADE C 42 4

P VALUE - 0.022 CHI SQUARE TEST

SIGNIFICANT

Chart 26. CTP GRADE VS VARICEAL BLEED

29

42

25

4

GRADE B GRADE C

VARICEAL BLEED PRESENT VARICEAL BLEED ABSENT

70

Table 27. OGD SCOPE FINDINGS VS PLATELET COUNT

OGD SCOPE

PLATELET COUNT (X 10³)

MEAN SD

NORMAL 182.41 79.95

GRADE I VARICES 107.73 33.22

GRADE II VARICES 72.17 24.48

GRADE III VARICES 46.52 19.33

P VALUE - 0.001 UNPAIRED T TEST

ANOVA

Chart 27. OGD SCOPE FINDINGS VS PLATELET COUNT

182.41

107.73

72.17

46.52

NORMAL GRADE I VARICES GRADE II VARICES GRADE III VARICES

71

Table 28. OGD SCOPE FINDINGS VS PROTHROMBIN TIME

OGD SCOPE

PROTHROMBIN TIME

MEAN SD

NORMAL 20.68 4.61

GRADE I VARICES 21.57 3.31

GRADE II VARICES 24.05 4.87

GRADE III VARICES 24.84 8.95

P VALUE - 0.002 UNPAIRED T TEST

ANOVA

Chart 28. OGD SCOPE FINDINGS VS PROTHROMBIN TIME

20.68 21.57

24.05 24.84

NORMAL GRADE I VARICES GRADE II VARICES GRADE III VARICES

72

Table 29. OGD SCOPE FINDINGS VS INR

OGD SCOPE

INR

MEAN SD

NORMAL 1.47 0.23

GRADE I VARICES 1.54 0.33

GRADE II VARICES 1.71 0.34

GRADE III VARICES 1.77 0.28

P VALUE - 0.001 UNPAIRED T TEST

ANOVA

Chart 29. OGD SCOPE FINDINGS VS INR

1.47 1.54

1.71 1.77

0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2

NORMAL GRADE I VARICES GRADE II VARICES GRADE III VARICES

73

DISCUSSION

The study involving 100 patients done at Coimbatore government medical college hospital has thrown light over the haematological abnormalities of chronic liver disease. The results of this study confirms with previous published reports.

In this study involving 100 patients, 86 patients were males and 14 were females. This gender distribution was comparable to a study done by Anbazhagan et al in which 88% were males and 12% were females.

Mean age of the study population in our study was 47.39 with 34%

patients belong to 41-50 years of age. 39% patients belong to more than 50 years of age and 27% patients were 40 years or younger.

Most common etiology found in our study was alcoholism seen in 67% of patients followed by Viral hepatitis observed in 13% cases (hepatitis B in 8%, hepatitis C in 5%) and NASH-related CLD in 8% of cases. These observations were comparable to the study by Gautam Ray et al. They showed alcohol as the most common aetiology for the CLD (in 42% cases) followed by viral hepatitis (in 31% cases- 21% cases were hepatitis B and 10% cases were hepatitis C) and cryptogenic causes (in 25% cases) and mean age of alcohol-related CLD was 48.4 years.

Most common presenting symptom in the study population is abdominal distension which is present in all 100 patients followed by

74

Upper GI bleed in the form of hemetemesis and/or malena, present in about 54 patients

In the study population, about 28 patients had hepatic encephalopathy of which 14 had minimal and 14 had overt / profound hepatic encepathopathy features.

ANAEMIA AND RBC ABNORMALITIES:

88% of patients in this study had anaemia. Severe anaemia (Hb <8 gm%) was observed in 29% patients. Mean Hb of the study group was 9.142 gm%. Mean Hb in females were lower than males (7.52 gm% vs.

9.40 gm%). Mean Hb was less in alcohol-related CLD when compared to CLDs (8.63 gm% vs 10.16 gm%) due to other aetiologies.

Anbazhagan et al found out 80% of the study population were anaemic and in 30% cases Hb was less than 6 gm%. A study by Rosario Gonzalez-Casas et al showed that anaemia due to various aetiologies occur in 75% cases of CLD patients. E. Halleys Kumar et alobserved 86% cases were anaemic with 16% of patients had Hb of less than 6 gm%. These results were comparable with our study.

Alcoholics are at more risk of developing anaemia by various mechanisms, which maybe the reason for increased prevalence of anaemia in alcoholic CLDs, observed in this study.

Most common anaemia observed was normocytic normochromic anaemia (41%). 23% had macrocytic anaemia, 14% had microcytic

75

hypochromic anaemia and in 14% cases,dimorphic blood picture was observed. This was in part comparable with the study done by Anbazhagan et al. In that study, most common anaemia observed was normocytic normochromic (in 62.5% cases), microcytic anaemia in 25%

cases, macrocytic anaemia in 10% cases and dimorphic anaemia in 2.59% cases and a study done by E. Halleys Kumar et al also showed normocytic normochromic anaemia as the most common anaemia (52.3%) followed by microcytic anaemia (27.9%), 17.44% anaemia‟s had macrocytic blood picture.

But in case of our study, the second most cause of anaemia is macrocytic anaemia. This may be due to increased alcohol consumption in the study group, which would have influenced their peripheral picture.

ABNORMALITIES OF WBCS

According to Sheila Sherlock, leucopenia and thrombocytopaenia are commonly found in cirrhotics. But, according to Oxford Textbook of Hepatology, leucocyte abnormalities in liver disease may be due to the underlying disease or its therapy and range from neutrophilia to neutropenia and lymphopaenia.

In our study group, all the 100 patients, WBC total count are in the range of 1,300 to 18,200 cells per mm3. About 17 patients had

76

leucocytosis, which were mostly due to community-required infection, nosocomial infection, spontaneous bacterial peritonitis and secondary peritonitis due to repeated peritoneal paracentesis.

About 50% of patients with leucocytosis had high-grade fever and all patients with leucocytosis had increased cell count mostly of polymorphs in ascitic fluid analysis, which suggests the presence of peritonitis in this group of patients. Leucopenia was observed in 19%

patients and the rest had normal WBC count.

77

VARIOUS PARAMETERS COMPARED AND THEIR SIGNIFICANCE

S.No. PARAMETERS P VALUE

1 ALCOHOLIC VS MCV 0.012

2 ALCOHOLIC VS PANCYTOPENIA 0.001

3 PLATELET COUNT VS UGI BLEED 0.001

4 PROTHROMBIN TIME VS UGI BLEED 0.013

5 INR VS UGI BLEED 0.030

6 CTP SCORE VS VARICES GRADING 0.022

7 PLATELET COUNT VS VARICES GRADING 0.001 8 PROTHROMBIN TIME VS VARICES GRADING 0.002

9 INR VS VARICES GRADING 0.001

78

PLATELET ABNORMALITIES

Thrombocytopenia was found out in 80% of patients in our study.

Platelet count of most of the patients ranges between 0.5 to 1 lakh/mm³. In our study, thrombocytopenia observed in 80% cases probably since most of the patients were having advanced liver disease, as evidenced by mean CTP score of 9.72. 46% of patients belong to child C class (CTP score 10 or more) and 54% belong to child B class (CTP 7 to 9). Platelet count decreases as CTP score increases (p 0.001). This implies that patients with more advanced end-stage disease tend to have a higher degree of thrombocytopenia than those with less advanced CLDs.

PANCYTOPENIA

Out of 100 patients in the study , 35 patients had pancytopenia, of which 33 patients are alcoholic. This indicates there is a definite positive co-relation between alcoholism and pancytopenia. This co-relates with various other articles, which substantiates the above said co-relation.

.