Study of Lipid Profile in Anemia

A STUDY OF LIPID PROFILE
IN
ANAEMIA
by
Dr. Zayed Abdulla
Dissertation Submitted to the

Rajiv Gandhi University Of Health Sciences, Karnataka, Bangalore
In partial fulfillment
of the requirements for the degree of
Doctor of Medicine
in
General Medicine
Under the guidance of
Professor Chikkalingaiah. M.D.
Department of General Medicine

Kempegowda Institute of Medical Sciences
V.V. Puram, Bangalore
2005
Rajiv Gandhi University Of Health Sciences, Karnataka, Bangalore
DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation entitled A Study of Lipid Profile in
Anaemia is a bonafide and genuine research work carried out by me under the
guidance of Dr. Chikkalingaiah M.D., Professor of Medicine, Kempegowda Institute of
Medical Sciences, Bangalore and Dr. Mahadevappa PhD, Professor of Biochemistry,
Kempegowda Institute of Medical Sciences, Bangalore.
Date :
Signature of the Candidate
Place : Bangalore
Name: Dr. Zayed Abdulla
II
CERTIFICATE BY THE GUIDE
This is to certify that the dissertation entitled A Study of Lipid Profile in
Anaemia is a bonafide research work done by Dr. Zayed Abdulla in partial

fulfillment of the requirement for the degree of Doctor of Medicine.
Date :
Signature of the Guide
Place : Bangalore
Name: Dr. Chikkalingaiah. M.D.

Professor of Medicine,
Department of Medicine,
Kempegowda Institute of
Medical Sciences, Bangalore.
III
CERTIFICATE BY THE CO-GUIDE
Anaemia is a bonafide research work done by Dr. Zayed Abdulla in partial

fulfillment of the requirement for the degree of Doctor of Medicine.
Date :
Signature of the Co-Guide
Place : Bangalore
Name: Dr K.L. Mahadevappa, Ph.D.

Professor of Biochemistry,
Department of Biochemistry,
IV
ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF THE

INSTITUTION
Anaemia is a bonafide research work done by Dr. Zayed Abdulla under the guidance
of Dr. Chikkalingaiah M.D., Professor of Medicine, Kempegowda Institute of Medical
Sciences, Bangalore.
Seal & Signature of the HoD
Seal & Signature of the Principal
Name: Dr. V. Channaraya. M.D., DNB, F.I.C.C.,
Name: Dr. M. K. Sudarshan. M.D.,
Professor & HoD,
Principal,
Department of Medicine,

Date :
Date :
Place : Bangalore
Place: Bangalore
COPYRIGHT
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 / thesis in print or
electronic format for academic / research purpose.
Date :
Place : Bangalore
Rajiv Gandhi University of Health Sciences, Karnataka
VI
ACKNOWLEDGEMENT
I would like to take this opportunity to express my deep sense of gratitude towards
Dr. Chikkalingaiah. M.D., Professor of Medicine, Kempegowda Institute of Medical
Sciences, Bangalore, for his invaluable guidance, constant encouragement, and expert
suggestions, in spite of his busy schedule, which was most crucial in overcoming various
difficulties.
I would not have been able to complete this undertaking without Dr. K.L.
Mahadevappa PhD, Professor of Biochemistry, whose guidance and suggestions were of
utmost help.
I am deeply indebted to Dr. V. Channaraya. M.D., DNB, F.I.C.C., Professor and HoD,
Department of Medicine for his invaluable suggestions and insight.
I am extremely grateful to Dr. M.V Poornachandra. M.D., Professor and former
HoD, Department of Medicine for his supervision and keen interest in academic
activities.
I am grateful to Dr. Gowri Shankar M.D., Dr. H.V. Nataraju M.D., Dr. R. Manjunath
M.D., and Dr. Shivalingaiah M.D., Professors of Medicine, for their guidance and timely
help.
I am indebted to Dr. N.C. Srinivas Prabhu M.D., Dr. K.P. Balraj M.D., Dr. G.N.
Nagesh M.D. and Dr. R. Srinivas M.D., Associate Professors of Medicine for their
encouragement, valuable suggestions and healthy criticisms.
VII
I sincerely thank Dr. R. Vedavathi M.D. and Dr. K.C. Channappa M.D., Assistant
Professors of Medicine for their guidance and help given to me in this study. I am
grateful to Dr. H.D. Ramachandra Prabhu M.D. and Dr. C. Jagadish M.D., Lecturers in
Medicine, and Dr. H. Rajeev M.D., Dr. N. Venkataswamy M.D. and Dr. Ramakrishna M.D.,
Senior Residents in Medicine for their moral support during my study period.
I am indebted to Dr. K.M. Govindaraju M.S., Medical Superintendent, KIMS

Hospital, Dr. J. Ramachandra M.S., Administrative Medical Officer, KIMS Hospital, Dr.
M.K. Sudarshan M.D., Principal, KIMS, Dr L. Krishna M.D., former Principal, KIMS and
Dr. Vasantha Kumar.S. M.D., D.G.O., Vice Principal, KIMS, for permitting me to carry out
this work.
My thanks are due to the staff of the Departments of Pathology and Biochemistry
for helping me carry out the required investigations. I am indebted to Mr. K.P Suresh,
Statistician, National Institute of Animal Nutrition and Physiology, Bangalore for his
generous help. I am grateful to all my friends and colleagues for their untiring support. I
thank all others who have assisted me in some form or the other in the preparation of this
work. Last but not the least, I am grateful to all those patients who were the subjects for
this study, without whose co-operation this work would not have been possible.
Date :
Place : Bangalore
VIII
LIST OF ABBREVIATIONS USED

(in alphabetical order)
2,3-BPG
2,3-biphosphoglycerate
AIDS
Acquired immune deficiency syndrome
Apo
Apolipoprotein
BMI
Body mass index
CETP
Cholesteryl ester transfer protein
CHD
Coronary heart disease
CoA
Coenzyme A
DM
Dimorphic anaemia
DNA
Deoxyribo nucleic acid
FADH
Reduced flavin adenine dinucleotide
FBS
Fasting blood sugar
FH
Familial hypercholesterolemia
G6PD
Glucose 6 phosphate dehydrogenase
GIT
Gastrointestinal tract
GM-CSF
Granulocyte-macrophage colony stimulating factor
GPE
General physical examination
Hb
Haemoglobin
HCL
Hairy cell leukemia
HDL
High density lipoprotein
HMG CoA
3-hydroxy-3-methylglutaryl coenzyme A
HMP
Hexose monophosphate
IX
HSPG
Heparan sulphate proteoglycans
IDL
Intermediate density lipoproteins
JVP
Jugular venous pulse
KIMS
Kempegowda Institute of Medical Sciences
LCAT
Lecithin:Cholesterol acyl transferase
LDL
Low density lipoprotein
LP(a)
Lipoprotein a
LPL
Lipoprotein lipase
LRP
Low density lipoprotein receptor related protein
MCH
Mean corpuscular haemoglobin
MCHC
Mean corpuscular haemoglobin concentration
MCP-1
Monocyte chemoattractant protein 1
MCV
Mean corpuscular volume
MH
Microcytic hypochromic anaemia
MPD
Myeloproliferative disorder
MTP
Microsomal transfer protein
NADH
Reduced nicotinamide adenine dinucleotide
NCEP
National cholesterol education program
NH
Normocytic hypochromic anaemia
NN
Normocytic normochromic blood picture
PPBS
Post prandial blood sugar
RBC
Red blood cell
RBS
Random blood sugar
SAP
Serum alkaline phosphatase
SD
Standard deviation
SGOT
Serum glutamate oxaloacetate aminotranferase
SGPT
Serum glutamate pyruvate aminotransferase
T3
3,5,3-Triiodothyronine
T4
Thyroxine
TSH
Thyroid stimulating hormone
VLDL
Very low density lipoprotein
XI
ABSTRACT
Background & Objectives: Anaemia is reported to be associated with lowering in all
lipid subfractions. This study was conducted to study the clinical features of anaemia,
effect of anaemia on lipid profile, and effect of severity and type of anaemia on lipid
profile
Methods: The data for this study was collected from patients who presented to KIMS
hospital from June to June 2005. 100 anaemic cases and 100 non anaemic age and sex
matched controls underwent clinical assessment and relevant investigations, including
lipid profile estimation.
Results: Cases younger than 50 years were found to be more likely to have severe
anaemia. Fatigue and pallor were the most common clinical features. Clinical features
were more common among cases with severe anaemia. The mean total cholesterol (132.2
29.0 vs 173.4 20.3, P<0.01), HDL (31.0 6.7 vs 38.8 7.1, P<0.01), LDL (79.7
25.0 vs 110.1 16.6, P<0.01), VLDL (21.6 6.3 vs 24.5 6.2, P<0.01) and triglyceride
(108.1 31.3 vs 122.5 30.6, P<0.01) levels, along with TC/HDL (4.4 0.8 vs 4.6
0.7, P<0.05) and LDL/HDL (2.6 0.7 vs 2.9 0.6, P<0.01) ratios were significantly
decreased in cases compared to controls. There was a larger reduction in mean total
cholesterol, HDL, LDL, VLDL and triglyceride levels, along with TC/HDL and
LDL/HDL ratios with increased severity of anaemia (P<0.05). Type of anaemia did not
have a significant effect on the lipid levels (P>0.05).
XII
Interpretation
&
Conclusion:
Anaemia
is
associated
with
significant
hypocholesterolemia, with lowering in all lipid subfractions. The extent of

hypocholesterolemia is proportional to the severity of anaemia. The type of anaemia has
no effect on the hypocholesterolemia seen in anaemia. Further studies are required to
study the long term effect of anaemia on the risk of developing atherosclerosis, and to
study the long term effect of treatment of anaemia on lipid levels and cardiovascular
morbidity and mortality.
Keywords
Anaemia; Cholesterol; Hypocholesterolemia; Lipid Profile
XIII
TABLE OF CONTENTS
Page No.
1. Introduction
01
2. Objectives
02
3. Review of Literature
03
a) Historical review
03
b) Lipid Biochemistry and Cholesterol Metabolism
05
c) Anaemia
33
d) Anaemia and Hypocholesterolemia
54
4. Methodology
65
5. Results
70
6. Discussion
96
7. Conclusion
103
8. Summary
105
9. Bibliography
106
10. Annexures
115
I. Proforma
115
II. Master Charts
122
a) Master Chart (Cases)

b) Master Chart (Controls)
XIV
LIST OF TABLES
Sl.No
Table
Page No
Age distribution with haemoglobin levels in cases and controls
70
Sex distribution between case and controls
72
Distribution of cases according to type and severity of anaemia
73
Symptoms and severity of anaemia
76
Symptoms and type of anaemia
77
GPE and severity of anaemia
81
GPE and type of anaemia
82
Pulse rate, blood pressure and BMI with severity of anaemia
84
Pulse rate, blood pressure and BMI with type of anaemia
86
10
Systemic examination and severity of anaemia
88
11
Systemic examination and type of anaemia
89
12
Anaemia and lipid profile
91
13
Severity of anaemia and lipid profile
93
14
Type of anaemia and lipid profile
95
XV
LIST OF FIGURES
Sl.No
Figure
Page No
Age distribution in cases and controls
71
Age and severity of anaemia
71
Sex distribution in cases and controls
72
Symptoms
74
79
Pulse rate
84
Blood pressure
85
Body mass index
85
Pulse, blood pressure & BMI with types of anaemia
86
10
Systemic examination
87
11
Anaemia and lipid profile
91
12
Severity of anaemia and lipid profile
93
XVI
1. Introduction1
Current data indicate that serum lipid levels are significantly correlated with the risk
of atherosclerosis, which causes coronary artery disease, cerebrovascular disease and
peripheral vascular disease, important causes for mortality and morbidity worldwide2.
Anaemia is a common disorder in India. Although it may be due to various causes,

iron deficiency is most commonly responsible. Anaemia has been reported to have a
beneficial effect on the lipid profile. The lowering of lipid levels is not related to the type
of anaemia. The decrease in serum cholesterol is not due to a specific lowering of any of
the serum lipoprotein families; hypocholesterolemia is caused by a proportional reduction
in all the major lipoprotein families. This may have a beneficial effect on the risk of
developing coronary artery disease, a disease to which Indians are particularly
susceptible.
The exact mechanism by which anaemia causes a fall in serum lipids is not known.
The simplest explanation is a dilution effect (the increased volume of serum in anaemia
carrying the same total load of cholesterol). Other possibilities are increased utilization of
cholesterol by proliferating cells, decreased endogenous synthesis of cholesterol by the
liver due to decreased liver oxygenation, elevated levels of granulocyte-macrophage
colony stimulating factor and enhanced receptor mediated removal of LDL in the bone
marrow. Correction of anaemia is associated with a rise in serum lipids.
2. Objectives
The following were the objectives of the study.
1) To study the demographic characteristics and clinical features in cases with
anaemia.
2) To study the lipid profile in anaemia as compared with that in age and sex
matched controls.
3) To correlate the extent of changes, if any, in the various lipid sub fractions with
the severity of anaemia.
4) To correlate the changes in the lipid profile to different types of anaemia.
3. Review of Literature
a) Historical Review3
Babington in 18th century showed that fat gives a milky appearance to plasma. In
1780, Hawson described two forms of lipemia, one the alimentary and the other
spontaneous and pathological. Fischer revived the subject in 1903 and listed the
conditions in which milky appearance of blood was observed.
Neisser, Derlin and later Janel reported increased lipid levels in diabetic patients.
Klemperer and Umber showed conclusively that other lipids like phospholipids, sterols
and steroids are frequently increased in diabetic patients.
Grigaurt in 1910 developed a rapid method of assaying cholesterol. Chaufford,

Laroche and Grigaurt in the 14th French Medical Congress at Brussels held in 1920 put
forward the theory that there are two types of lipaemia, visible lipaemia and masked
lipaemia. Widal, Weill and Landet did substantial work on this.
Plasma lipoproteins were first recognized by the Frenchman Macheboef in 1920.

He found that serum treated with ammonium sulphate under specified conditions led to
the precipitation of a fraction containing lipid and protein of relatively constant
composition. In the 1940s, Oncley and colleagues applied the technique of Cohn fraction
to separate lipoproteins on the basis of density and sedimentation velocity in the
analytical centrifuge.
Havel, Eder and Bragdon introduced the procedure of preparative ultracentrifugation to separate and isolate lipoproteins. Ultracentrifugation is needed to
separate all lipoproteins except chylomicrons.
Lees and Hatch improved the technique of paper electrophoretic separation of

plasma lipoproteins through the use of albuminated buffer.
Frerickson, Levy and Lees used paper electrophoresis in conjunction with heparin
or manganese precipitation and preparative ultacentrifugation to establish a system for
classifying plasma lipoprotein disorders based on which family or families of lipoproteins
were elevated.
Rifkind and Gale4,5 in 1967 showed that anaemia was associated with
hypocholesterolemia, and that the decrease in serum cholesterol was not due to a specific
lowering of any of the serum lipoprotein families, and that hypocholesterolemia was
caused by a proportional reduction in all the major lipoprotein families.
In 1970, a study was conducted in 4,070 women6, which found a mean difference in
cholesterol between women with haemoglobin levels above and below 10.5 g/dL of 30
mg/dL. Treatment of anaemia led to rise in serum cholesterol levels. A study by
Westermann7 in 1975 examined the relationship between hypocholesterolemia and
various types of anaemia. This study showed that plasma cholesterol level is closely
related to haematocrit levels, regardless of the type of anaemia.
b) Lipid Biochemistry and Cholesterol Metabolism8

Lipids are hydrophobic molecules that are insoluble or minimally soluble in
water. They are found in cell membranes, and serve as a major form of stored nutrients,
as precursors of steroid hormones and as extracellular and intracellular messengers.
Lipoproteins transport complex lipids in the blood as water-soluble complexes.
Classes of Lipids8
Fatty Acids
Fatty acids vary in length and in the number and position of double bonds.
Saturated fatty acids lack double bonds, monounsaturated fatty acids have one double
bond, and polyunsaturated fatty acids have two or more. They are a major source of
energy and can be esterified to form complex lipids.
Cholesterol
Cholesterol is a four-ring hydrocarbon with an eight-carbon side chain. It is a
major component of cell membranes and a precursor of steroid hormones and bile acids.
Complex Lipids
Triglycerides (Triacylglycerol)
Triglycerides consist of three fatty acid molecules esterified to a glycerol
molecule. Diglycerides contain two fatty acids, and monoglycerides have only one fatty
acid per glycerol molecule. Triglycerides serve to store fatty acids.
Phospholipids
Phospholipids have fatty acids esterified at two of the three hydroxyl groups of
glycerol. The third hydroxyl group is esterified to phosphate (phosphatidic acid).
Phosphatidic acid is esterified to the hydroxyl group of a hydrophilic molecule, such as
choline, serine, or ethanolamine.
Cholesterol Metabolism9
Cholesterol Biosynthesis
Cholesterol is either absorbed from the diet or synthesized in the body. It is
produced in many organs including liver, skin, adrenals, gonads, brain and intestine.
Cholesterol biosynthesis begins with acetate. Three molecules of acetate are

condensed to form 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), which is then
converted to mevalonic acid by the enzyme HMG-CoA reductase. Mevalonic acid is
converted to cholesterol via a series of steps. The rate-limiting step is HMG-CoA
reductase, which is under feedback control by the cholesterol content of the cells.
Cholesterol is not catabolised. It must be either excreted as free cholesterol in the

bile or converted to bile acids and secreted into the intestine, both of which undergo
enterohepatic circulation.
Cholesterol 7-Hydroxylase
This enzyme converts free cholesterol to 7-hydroxycholesterol. This is the ratelimiting step in bile acid synthesis, and it is under feedback regulation by bile acids.
Low Density Lipoprotein Receptor

This receptor is present on the surface of all cells. It mediates the uptake of
cholesterol-rich lipoproteins such as LDL from the blood. It binds to apolipoproteins B100 and E. The number of LDL receptors on the surface of a cell is regulated by its
cholesterol content. This keeps the intracellular cholesterol concentration relatively
constant.
Acyl-Coenzyme A: Cholesterol Acyltransferase

Acyl-coenzyme A: cholesterol acyltransferase is an enzyme of the endoplasmic
reticulum, which esterifies free cholesterol that enters a cell by transferring an acyl group
from long-chain fatty acyl-CoA to free cholesterol. The hydrolysis of cholesterol esters
by cholesterol ester hydrolase generates free cholesterol, either for efflux from the cells
or to act as a biosynthetic substrate.
Digestion and Absorption of Lipids10,11

Digestion
The digestion of lipids begins in the oral cavity by lingual lipase secreted by the
dorsal surface of the tongue (Ebners glands), but it is not of much significance.
The stomach secretes gastric lipase, which is the main preduodenal lipase. It
initiates lipid digestion by hydrolyzing triacylglycerols. The released hydrophilic shortand medium-chain fatty acids are absorbed via the stomach wall and enter the portal vein.
Most of the digestion of dietary lipids occurs in the intestine by pancreatic

enzymes. They are lipase, colipase, 100,000-kDa bile salt-activated lipase, cholesterol
esterase and phospholipase A2. In addition, bile salts are also involved in the digestion of
lipids. Bile salts reduce surface tension and emulsify fats. This increases the surface area
available for digestion.
Pancreatic lipase acts on triacylglycerols. It easily hydrolyzes the fatty acid

esterified to the 1st carbon atom of glycerol, forming 2,3 diacylglycerol and one molecule
of fatty acid. The 2,3 diacylglycerol is then further digested by the lipase, the products are
2-monoacylglycerol and a fatty acid molecule.
Bile salt-activated lipase catalyzes the hydrolysis of cholesterol esters, esters of

fat-soluble vitamins, and phospholipids, as well as triglycerides.
Cholesterol esters are hydrolyzed to cholesterol and fatty acids by cholesterol

esterase. Phospholipase A2 hydrolyzes the ester bond in the 2 position of
glycerophospholipids to form lysophospholipids, which aid in emulsification and
digestion of lipids.
Absorption
The water-soluble products of lipid digestion are absorbed directly into the portal
vein. These include glycerol and fatty acids with chain length of less than 10-12 carbon
atoms.
The other products of lipid digestion are 2-monoacylglycerols, long chain fatty
acids, cholesterol, phospholipids and lysophospholipids. They diffuse into micelles and
liposomes consisting of bile salts, phosphatidylcholine, and cholesterol, furnished by the
bile. Micelles are spherical particles with a hydrophilic exterior and hydrophobic core.
They allow the products of lipid digestion to be transported through the aqueous
environment of the intestinal lumen to the brush border of the mucosal cells, where they
are absorbed into the intestinal cells.
Within the intestinal mucosal cells, fatty acids are re-esterified to form
triglycerides and along with cholesterol, phospholipids, apoproteins C, E and A, are
incorporated into chylomicrons. Cholesterol and lysophospholipids are also re-esterified
with fatty acids to form cholesterol esters and phospholipids. Chylomicrons are formed in
golgi bodies.
The chyle formed by intestinal mucosal cells loaded with chylomicrons is

transported through lacteals into the thoracic duct and then emptied into the systemic
circulation.
Triglyceride and Free Fatty Acid Metabolism9

Storage and Use
Free fatty acids are released from triglycerides of chylomicrons and VLDL
through the action of lipoprotein lipase (LPL). It is bound to the capillary endothelial
cells. In adipose tissue, high levels of glucose and insulin promote the conversion of free
fatty acids to triglycerides for storage. Triglyceride synthesis is catalyzed by the enzyme
acyl-CoA: diacylglycerol Acyltransferase (DGAT).
Fatty Acid release from Adipose Tissue

Numerous hormones such as catecholamines, corticotropin, glucagons, placental
lactogen,
prolactin,
thyrotropin, vasoactive
intestinal
polypeptide,
vasopressin,
glucocorticoids and growth hormone promote lipolysis and release of fatty acids into the
bloodstream. These hormones activate hormone-sensitive lipase. Insulin, gastric
inhibitory polypeptide, oxytocin, prostaglandin and somatomedins act to inhibit
hormone-sensitive lipase and lipolysis.
Fatty acids formed by lipolysis are released into the bloodstream from adipocytes.
They bind to albumin and circulate in the plasma. Glycerol is taken up by the liver and
kidney for triglyceride synthesis or for gluconeogenesis. Fatty acids are taken up by
either the liver or muscle.
Fatty Acid Oxidation and Ketogenesis

Both these processes take place in the mitochondria, except for very long chain
fatty acids, which are oxidized in the peroxisomes. Fatty acids are converted to CoA
derivatives and undergo beta-oxidation, which produces acetyl-CoA, FADH and NADH.
Acetyl CoA enters the citric acid cycle, whereas FADH and NADH enter the electron
transport system.
10
If the free fatty acid flux to the liver is massively increased, as in uncontrolled
diabetes mellitus or prolonged fasting, it exceeds the livers ability to synthesize VLDL,
resulting in accumulation of acetyl-CoA, FADH and NADH in the mitochondria. This
leads to ketogenesis.
Fatty Acid Biosynthesis

Fatty acids are synthesized from acetyl-CoA in the cytosol. Eight acetyl-CoA
molecules are condensed to form palmitic acid in a series of reactions involving the
enzymes fatty acid synthetase and acetyl-CoA carboxylase. Longer chain fatty acids,
such as stearic acid or oleic acid, are synthesized from palmitic acid by chain extension.
Apolipoproteins12
Apolipoproteins are the protein moiety of lipoproteins. They act as structural
components of lipoproteins, activate and inactivate enzymes involved in lipoprotein
metabolism, and bind lipoproteins to cell surface receptors. Each lipoprotein has a
particular, nearly constant apolipoprotein composition.
Apolipoprotein B13
In human plasma, apo-B occurs in two forms, apo-B100 and apo-B48. Apo B-100
is synthesized in the liver and serves as a structural protein of VLDL, IDL and LDL.
Each of these particles contains one molecule of apo B-100. Apo B-100 serves as a ligand
for the LDL receptor. Apo-B48 is a structural constituent of chylomicrons. It is
synthesized in the intestine. It cannot bind to the LDL receptor.
11
Apolipoprotein E
Apolipoprotein E is a constituent of chylomicrons, chylomicron remnants, VLDL,
IDL and HDL1. It serves as the ligand for LDL receptor and chylomicron remnant (apoE) receptor. It is synthesized in various tissues, including the liver and macrophages.
Apo-E functions in two aspects of lipid transport. The first involves chylomicron and
VLDL transport. The second aspect involves the redistribution of lipids among cells
within a tissue or organ.
Apolipoprotein AI
Apo-AI is synthesized by the human intestine and liver and is a constituent of
chylomicrons and HDL. In addition to its role as a structural protein in HDL, apo-AI
activates lecithin: cholesterol acyltransferase, which esterifies free cholesterol on HDL
particles.
Apolipoprotein AII
Apo-AII is synthesized primarily in the liver. It is found together with apo-AI on
a subfraction of HDL referred to as LpAI/AII particles. Apo-AII may play a role in the
activation of hepatic lipase and the inhibition of LCAT.
C Apolipoproteins
They are apo-CI, apo-CII and apo-CIII. They are synthesized primarily by the
liver and readily exchange among various lipoproteins. HDL serves as a reservoir for the
C apolipoproteins, which can then be transferred to triglyceride-rich lipoproteins. Apo-CI
12
modulates remnant binding to receptors and activates LCAT. Apo-CII acts as a cofactor
for lipoprotein lipase. Apo-CIII modulates remnant binding to receptors.
Lipoprotein Receptors12
Low Density Lipoprotein Receptor
The LDL receptor functions in the uptake of apo-B100 and apo-E containing
lipoproteins, including LDL, chylomicron remnants, VLDL, VLDL remnants, IDL, and
HDL1. The expression of LDL receptors on the cell surface is regulated by the
intracellular cholesterol concentration.
Low Density Lipoprotein Receptor-Related Protein

The LRP is an integral membrane receptor. It binds with high affinity to apo-E
enriched chylomicron remnants and VLDL remnants and internalizes them. LRP does not
bind LDL.
Very Low Density Lipoprotein Receptor

The VLDL receptor binds apo-E containing lipoproteins and is present primarily
in muscle, fat and brain. It is absent from liver. It functions to deliver triglyceride-rich
lipoproteins to target tissues.
Apolipoprotein E Receptor 2
The apo-E receptor 2 is expressed primarily in the brain and to a lesser extent in
the placenta. It plays a role in lipoprotein metabolism in the central nervous system. It
also plays a role in normal brain development by transducing extracellular signals.
13
Scavenger Receptors
The scavenger receptors are a large family of receptors with specificities for a
broad range of unrelated ligands and involvement in a spectrum of physiologic processes,
including atherosclerosis, host defense and central nervous system disorders. These
receptors are characterized by their ability to interact with chemically modified LDL but
not with native LDL. LDL particles that are modified by acetylation, acetoacetylation, or
malondialdehyde are taken up by these receptors present on the macrophages, resulting in
marked cholesterol accumulation. Currently, there are five subclasses (A to E) of the
scavenger receptor family.
Enzymes and Transfer Proteins12

Lipoprotein Lipase
LPL is synthesized by adipocytes, by myocytes in skeletal and cardiac muscle,
and by macrophages. After secretion from adipocytes and myocytes, LPL is transported
to the surface of capillary endothelial cells of these tissues, where it attaches to HSPG
and interacts with chylomicrons and VLDL in the circulation and mediates the hydrolysis
of their triglycerides.
Hepatic Lipase
Hepatic lipase is synthesized by hepatocytes and is present on liver endothelial
cells and on HSPG in the space of Disse. It is transported from liver to the capillary
endothelium of the adrenals, ovaries and testes. It hydrolyzes triglycerides and excess
phospholipids in the final processing of chylomicron remnants. It binds heparan sulfate
14
and facilitates the interaction of remnant lipoproteins with LRP, thereby delivering these
lipoproteins to the receptor for internalization by hepatocytes. It completes the processing
of IDL to LDL. It converts HDL2 to HDL3 by removing triglyceride and phospholipids
from HDL2.
Lecithin: Cholesterol Acyltransferase

LCAT circulates in association with HDL in the plasma and esterifies free
cholesterol. This enzyme catalyzes the transfer of long-chain fatty acids from
phosphatidylcholine to the hydroxyl group at position 3 on cholesterol. The major
substrate for LCAT is the small HDL particle.
Cholesteryl Ester Transfer Protein

CETP transfers cholesterol esters from larger HDL to VLDL, IDL, and remnant
lipoproteins. In return, triglyceride from these lipoproteins is transferred to HDL.
Plasma Lipoproteins12
Chylomicrons
Chylomicrons are the largest of the plasma lipoproteins. They are composed of
98% to 99% lipid and 1% to 2% protein. Chylomicrons are present in postprandial
plasma and contain several apolipoproteins, including apo-B48, apo-AI, apo-AIV, apo-E
and the C apolipoproteins. The distinctive apolipoprotein is apo-B48, which is
synthesized only in the intestine.
15
Chylomicrons are produced by the epithelial cells of the small intestine

(duodenum and proximal jejunum). Free fatty acids and monoglycerides are synthesized
into triglycerides, which along with phospholipids and cholesterol, are used for
chylomicron formation in the golgi apparatus. They enter the mesenteric lymph and enter
the bloodstream via the thoracic duct.
LPL catalyzes the release of fatty acids from chylomicron triglycerides and
converts them into chylomicron remnants. These are cleared rapidly from the plasma by
the liver. The actual uptake of these particles by hepatocytes involves the LDL and LRP
receptors.
Very Low Density Lipoproteins

VLDLs are particles that float on ultra centrifugation at a density of less than
1.006 g/mL. They are composed of 85% to 90% lipid and 10% to 15% protein. The
distinctive apolipoprotein is apo-B100. VLDLs also contain apo-E and C apolipoproteins.
VLDLs are synthesized by the liver. The major apolipoproteins of newly

synthesized VLDLs are apo-B100, apo-E, and small amounts of the C apolipoproteins. In
plasma, VLDLs acquire additional C apolipoproteins and apo-E, primarily from HDL.
VLDL triglycerides are hydrolyzed by the actions of LPL and hepatic lipase. The
products of VLDL catabolism are IDLs. IDLs retain apo-B100 and apo-E. IDLs are
processed to LDLs by LPL with final processing by hepatic lipase. Approximately half of
16
VLDLs are converted to LDLs, and the remainder is cleared directly by the liver as
VLDL remnants and IDLs.
Intermediate Density Lipoproteins

IDLs are normally present in low concentrations in plasma and are intermediate in
size and composition between VLDL and LDL. Their primary proteins are apo-B100 and
apo-E. Their primary proteins are apo-B100 and apo-E. The IDLs are precursors of LDLs
and represent metabolic products of VLDL catabolism. IDLs may be further processed by
hepatic lipase or removed from the plasma by the LDL receptor.
Low Density Lipoproteins

LDLs are the major cholesterol carrying lipoproteins in the plasma. LDLs are
composed of 75% lipid and 25% protein. Apo-B100 is the principal protein in these
particles, along with trace amounts of apo-E.
LDLs are the end products of lipase-mediated hydrolysis of VLDLs. As the

triglyceride-rich core of the larger VLDL particles are removed, the surface lipids and
proteins are remodeled and excess surface constituents are transferred to HDL, resulting
in the formation of a small, cholesterol-rich LDL devoid of all apolipoproteins except
apo-B100.
About 75% of LDL is taken up by hepatocytes. Other tissues take up smaller

amounts of LDL. Most of the uptake is mediated by the LDL receptor and apo-B100.
17
LDL serves as a source of cholesterol for many cells. Cholesterol taken up by the
liver has several fates: membrane biosynthesis, VLDL biosynthesis, excretion in bile and
conversion to bile acids. Cholesterol is used as a precursor for steroid hormone
production in the adrenals, ovaries, and testes. In other tissues, cholesterol is used in
membrane biosynthesis for cell repair and proliferation.
High Density Lipoproteins

HDLs are small particles that float at densities of 1.063 to 1.21 g/ml. They are
subdivided into two classes, HDL2 and HDL3. HDLs contain about 50% lipids and 50%
protein. Their major proteins are apo-AI, apo-AII, and smaller amounts of C
apolipoproteins and apo-E. Apo-E is a minor component of a subclass of HDL referred to
as HDL1.
HDLs originate from three sources. First, the liver secretes an apo-AIphospholipid disc called precursor HDL. Second, the intestine directly synthesizes a
small apo-AI containing HDL particle. Third, HDLs are derived from surface material
that comes from chylomicrons and VLDLs during lipolysis.
The precursor HDL particles are excellent acceptors of free cholesterol, which
gets esterified by LCAT and moves away from the surface of the particle, forming a
cholesterol ester-rich core (HDL2). As HDL2 accepts more cholesterol, it enlarges and
gets converted to HDL3. HDL2 can also acquire apo-E to form HDL1.
18
HDLs have an important role in the process of reverse cholesterol transport.

HDLs acquire cholesterol from cells and transport it to liver or other cells that require
cholesterol. HDL3 particles are converted to HDL2 and then to HDL1. Apo-E, which is
found on HDL1, targets this subclass to cells expressing the LDL receptor. A second
pathway involves CETP, which transfers cholesterol ester from HDL2 to VLDL, IDL,
LDL and remnants.
HDL2 particles are partially depleted of cholesterol esters and enriched in

triglycerides by the action of CETP. Hepatic lipase then acts on these particles to convert
them to HDL3, thus perpetuating the HDL2-HDL3 cycle. High levels of HDL are
associated with a lower incidence of CHD, and vice versa. High HDL levels promote
redistribution of cholesterol away from the artery wall.
Lipids and Atherosclerosis2

Atherosclerosis causes a reduction of blood flow and insufficient delivery of
oxygen and nutrients to affected organs. Insufficient oxygen results in ischemia or
infarction, leading to angina or myocardial infarction in the case of restricted blood flow
to the heart muscle, to stroke with reduced blood flow to the brain, or to intermittent
claudication with restricted blood flow to the lower extremities. CHD is the leading cause
of death in most countries.
The restricted arterial blood flow in atherosclerosis is caused by changes in the

vessel wall characterized by lipid deposition and cell proliferation. Narrowing of the
vessel lumen leads to obstruction and unstable plaques susceptible to ulceration and
19
fissuring. The deposited lipids are derived from plasma lipoproteins, and elevated plasma
cholesterol is a major risk factor. Other important risk factors include low HDL levels,
cigarette smoking, hypertension, male sex, diabetes mellitus, obesity, stress, and lack of
exercise.
CholesterolDietHeart Hypothesis
The cholesterol-diet-heart hypothesis states (1) that increased plasma cholesterol
concentrations increase the risk of CHD, (2) that diets high in fat (especially saturated
fat) and cholesterol result in increased levels of plasma cholesterol, and (3) that lowering
plasma cholesterol levels results in a decreased risk of CHD.
Epidemiological evidence
Several epidemiological studies have demonstrated a relation between plasma
cholesterol level and the risk of CHD14. The Multiple Risk Factor Intervention Trial15
showed that there is increased risk at levels above 200 mg/dl. The Seven Countries Study
also demonstrated a relation between an increased incidence of CHD and high plasma
cholesterol levels16.
Epidemiological studies have linked the intake of high levels of dietary fats,
especially saturated fats, with increased plasma cholesterol levels. Diets high in
cholesterol also tend to increase plasma cholesterol levels17. Therefore, restriction of
saturated fat and cholesterol is the cornerstone of dietary therapy to reduce elevated blood
cholesterol levels18.
20
Experimental Evidence in Humans

Compelling evidence supporting the cholesterol-diet-heart hypothesis comes from
several human clinical trials examining the efficacy of several lipid-lowering drugs in
reducing CHD. The results unequivocally demonstrated that lowering plasma cholesterol
levels reduces the risk of CHD19.
Atherogenic Lipoproteins
In addition to LDL, almost all classes of lipoproteins that contain apo-B (VLDL,
-VLDL, IDL, Lp(a), and oxidized LDL) are atherogenic. Lp(a) contains apo(a), which
may contribute to atherogenesis by mechanisms related to thrombosis. The atherogenic
potential of LDL differs among the various LDL size and density subclasses, with the
small, dense LDL subclass being the most atherogenic.
The LDL Paradox

Only low levels of normal plasma LDL are taken up by macrophages due to the
highly regulated LDL receptor pathway. The delivery of LDL to macrophages downregulates LDL receptor expression, thereby protecting the cells from over accumulation
of LDL. This leads to the LDL paradox, how do LDLs contribute to atherosclerosis if
only limited quantities are taken up by macrophages? The explanation is that LDLs that
have been modified are taken up by macrophages in an unregulated manner through
scavenger receptors unrelated to the LDL receptor.
A number of chemical modifications, including acetylation, acetoacetylation,

oxidation, and reaction with malondialdehyde, circumvents the LDL receptor pathway
21
and causes massive amounts of modified LDL to enter macrophages. Macrophages

themselves can cause these modifications in LDL.
Atherogenesis20,21
The key early event in atherosclerosis is the retention of atherogenic, cholesterolrich lipoproteins in the arterial sub endothelium. Oxidation22 and other modifications of
the retained lipoproteins initiate a series of responses that lead to the transformation of
healthy arteries into diseased, lesioned arteries.
One of the initial events in atherogenesis is the focal attachment of circulating

monocytes to the endothelial surface. Atherogenic lipoproteins retained in the sub
endothelium and areas of micro injury are responsible for this. Once adhered, the
monocytes migrate between endothelial cells, enter the sub endothelial space, and
differentiate into macrophages. Within the wall, LDLs become entrapped in the matrix
and undergo oxidation or further chemical modifications. The macrophages take up the
modified LDL and converts into foam cells.
Monocyte chemo attractant protein 1 (MCP-1), produced by endothelial and

smooth muscle cells, plays a role in further monocytes recruitment. Other growth factors
that have been implicated in atherosclerosis include platelet-derived growth factor, basic
fibroblast growth factor, insulin-like growth factors, interleukin-1, tumor necrosis factor,
and transforming growth factor . These factors stimulate smooth muscle cell
proliferation. Cytokines involved in atherogenesis include interleukin-1, interferon ,
tissue necrosis factor , interleukin-2, and the colony stimulating factors. These factors
22
act through a network of cellular interactions operating in a paracrine or autocrine

manner,
The first grossly visible atherosclerotic lesion is the fatty streak. Macrophages
accumulate in the sub endothelial space and are converted to foam cells. Fatty streaks
come and go, depending on the local stimuli present in the artery wall.
The fatty streak matures into a proliferative or fibrous plaque, which is raised and
begins to extend into the lumen of the vessel. The foam cells begin to necrose because of
the cytotoxicity of the accumulated lipid, leading to extracellular lipid deposition,
accompanied by collagen synthesis and smooth muscle cell migration and proliferation.
The surfaces of complicated lesions may become thrombogenic as endothelial

cells are lost. Platelets adhere to this surface, promoting thrombus formation.
Alternatively, a fissure forms in the unstable plaques and blood dissects into the artery
wall, leading to the formation of a large thrombus. Calcification is also a feature of late
lesions. Advanced lesions weaken the artery wall, causing aneurysms. Removal or
reduction of the atherogenic stimulus results in plaque regression, leaving a remnant
devoid of lipid that resembles a scar.
Hyperlipidemia23
Hyperlipidemia has been defined from population distributions as the upper 5% to
10% of values (i.e., the 90th to 95th percentile). Guidelines from the 2001 National
Cholesterol Education Program18 (NCEP) suggest that plasma cholesterol levels less than
23
200 mg/dl are desirable, that those between 200 and 240 mg/dl are borderline elevated,
and that levels greater than 240 mg/dl are high. Hypolipidemia can be defined as plasma
cholesterol concentrations less than 130 mg/dl.
Hyperlipidemia is caused by increased concentrations of plasma lipoproteins. One

or more classes of lipoproteins may accumulate in the blood stream because of increased
production or secretion into the circulation or because of decreased clearance or removal
from the circulation; in some cases, both processes coexist. Alterations resulting from
genetic defects are classified as primary disorders of lipid metabolism. Alternatively,
other factors that alter lipoprotein metabolism, such as diabetes mellitus or
hypothyroidism, lead to increased plasma lipoprotein concentrations; these are classified
as secondary disorders of lipid metabolism.
Primary Disorders of Hyperlipidemia23

Familial Hypercholesterolemia
Familial hypercholesterolemia is a disorder caused by mutations in the LDL
receptor gene that results in LDL receptor malfunction or absence, leading to elevated
LDL and total cholesterol levels.
The characteristic physical finding is the presence of tendon xanthomas, on the

Achilles tendon or extensor tendons of hands. Other findings are xanthelesma and
premature arcus corneae. Premature coronary artery disease is common24. The diagnosis
of FH is primarily clinical. It can be confirmed by culturing skin fibroblasts and
24
demonstrating a reduced ability of LDL to bind to receptors on the cells. Treatment

consists of a low fat diet and drug therapy.
Familial Defective Apolipoprotein B100

It is caused by a mutation in apo-B100, the ligand for the LDL receptor, that
results in high plasma LDL and total cholesterol levels. The clinical features include
isolated elevations of LDL-C, tendon xanthomas, xanthelasmas, and premature CAD.
Treatment consists of a low-fat, low-cholesterol diet and a combination drug regimen.
Familial Combined Hyperlipidemia

Familial combined hyperlipidemia is a common disorder of unknown genetic
cause associated with elevations of plasma cholesterol and triglyceride levels and
increased susceptibility to CHD. It is inherited as an autosomal dominant trait. The
features include moderate elevations of plasma cholesterol, triglycerides, or both.
Associated metabolic disturbances may include glucose intolerance, obesity, and
hyperuricemia.
Weight reduction and dietary management can help correct associated metabolic
abnormalities. Drug therapy should be directed at the predominant lipid abnormality.
Affected family members should be identified.
Type III Hyperlipoproteinemia

This is characterized by moderate to severe hypertriglyceridemia and
hypercholesterolemia caused by the accumulation of cholesterol-rich remnant particles.
25
The cause is mutations in apo-E that result in defective binding to lipoprotein receptors.
The presence of palmar xanthomas, which are planar xanthomas in the palmar creases, is
virtually pathognomic for this disorder. Tuberous or tuberoeruptive xanthomas are also
common. Premature vascular disease is common.
A vigorous search should be made to identify and treat obesity, alcohol

consumption, diabetes mellitus, and hypothyroidism. Dietary therapy should be aimed at
restricted total fat, saturated fat, and cholesterol, and at caloric restriction to reduce
weight. If dietary therapy and treatment of coexisting metabolic conditions yield
unsatisfactory results, drug therapy should be initiated.
Lipoprotein Lipase Deficiency

LPL deficiency is a rare, recessive disorder that results from mutations in the LPL
gene. It is usually recognized in infancy or childhood as a chylomicronemia syndrome,
which consists of marked hypertriglyceridemia associated with recurrent abdominal pain
or pancreatitis. The findings include eruptive xanthomas and lipemia retinalis.
Heterozygous
subjects
have
reduced
LPL
activity
and
mild
to
moderate
hypertriglyceridemia.
Initial treatment consists of a fat-free diet till plasma triglycerides reach a safe
level. Dietary fat restriction needs to be continued life long. Medium-chain triglycerides
can provide a source of fat in the diet. Fat-soluble vitamins should be supplemented.
Drug therapy for primary LPL deficiency is largely ineffective.
26
Apolipoprotein CII Deficiency

Apo-CII deficiency is a autosomal recessive disorder that causes a
chylomicronemia syndrome whose features include pancreatitis or recurrent bouts of
abdominal pain in children or young adults and lipemic serum after a 12-hour fast.
Heterozygotes may have slightly elevated triglyceride levels, but they do not develop
pancreatitis. Severe hypertriglyceridemia and pancreatitis in apo-CII_deficient patients
can be treated with transfusions of plasma, which contains apo-CII.
Familial Hypertriglyceridemia
Familial hypertriglyceridemia is characterized by increased plasma concentrations
of triglyceride-rich VLDLs. Obesity and insulin resistance is common. The genetic defect
is unknown.
In addition to dietary fat restriction, secondary disorders such as diabetes mellitus,

estrogen administration, or alcohol intake should be screened for and treated. Drugs that
lower triglyceride levels may be useful.
Elevated Plasma Lp(a)

This disorder consists of elevations of modified LDL particles in the plasma, in
which the apo-B protein of LDL is covalently bonded to apo(a). There are no
characteristic physical findings or lipoprotein patterns to suggest elevated Lp(a) levels. It
may however be suspected in patients with premature CHD. Of the hypolipidemic drugs
currently available, only niacin appears to lower plasma Lp(a) levels.
27
Polygenic Hypercholesterolemia
Polygenic hypercholesterolemia is diagnosed by excluding other primary genetic
causes, by the absence of tendon xanthomas, and by demonstrating that
hypercholesterolemia is present in no more than 10% of first degree relatives.
Sporadic Hypertriglyceridemia
Sporadic hypertriglyceridemia can be distinguished from familial syndromes by
the absence of hypertriglyceridemia in relatives. The condition is treated with dietary fat
restriction, treatment of secondary conditions that exacerbate hypertriglyceridemia, and
drugs that lower triglyceride levels.
Primary Disorders of High-Density Lipoprotein Metabolism23

Familial Hypoalphalipoproteinemia
The
autosomal
dominant
disorder
familial
hypoalphalipoproteinemia
is
manifested by low plasma HDL-C levels and an increased risk for premature CHD. There
are no characterictic physical findings, but there is often a family history of low HDL-C
levels and premature CHD. The genetic and metabolic defects that lead to low plasma
HDL-C levels are unknown.
Apolipoprotein AI mutations
Mutations in the apo-AI gene can decrease HDL formation and result in low
plasma HDL-C levels. Manifestations include a predisposition to premature CHD,
xanthomas, and corneal opacities.
28
Cholesteryl Ester Transfer Protein Deficiency

This is a rare disorder in which plasma HDL-C levels are increased because of
diminished activity of plasma CETP. Its features include marked elevations of plasma
HDL-C in homozygotes and possible protection against development of CHD.
Primary Genetic Hypolipidemias23

Familial Hypobetalipoproteinemia
It is an autosomal dominant disorder of apo-B metabolism. Heterozygotes are
usually asymptomatic and have low plasma cholesterol levels. They have an increased
lifespan due to a decreased risk for CHD. Homozygotes present at a young age with fat
malabsorption and decreased plasma cholesterol levels. It is associated with retinitis
pigmentosa, acanthocytosis, and a progressive neurologic degenerative disease resulting
from vitamin E deficiency.
Homozygotes should be treated with large doses of vitamin E orally (100 to 300
mg/kg/day) in order to prevent neurologic complications.
Abetalipoproteinemia
This is a rare autosomal recessive disorder caused by a deficiency in MTP, which
results in a virtual absence of apo-B containing lipoproteins in the plasma. Features are
malabsorption of fat and fat-soluble vitamins from the intestine, which leads to
neurologic disease secondary to vitamin E deficiency. It is treated with large oral doses of
vitamin E.
29
Secondary Disorders of Lipid Metabolism23

Diabetes Mellitus
Diabetes
Mellitus
exerts
profound
effects
on
lipid
metabolism.
Hypertriglyceridemia is found in up to one third of all diabetic patients. Diabetics also

frequently have high plasma levels of atherogenic lipoproteins and low plasma HDL.
In type 1 diabetes, insulin deficiency and poor glycemic control are associated
with increases in the plasma levels of triglycerides and apo-B-containing lipoproteins
because of effects on plasma lipid metabolism in peripheral tissues and the liver.
In type 2 diabetes the metabolic defect is related to insulin resistance and relative
insulin deficiency. The most common lipid abnormality in type 2 diabetes is a moderate
hyperlipidemia characterized by an increase in VLDL, accompanied by various degrees
of chylomicronemia. Plasma triglyceride and cholesterol levels are elevated, HDL-C
concentration may be low and IDLs are also increased. The hyperlipidemia in type 2
diabetes is accompanied by an increase in small dense LDLs which are particularly
atherogenic.
The mainstay of therapy is glycemic control. Decreasing insulin resistance

through weight reduction can have dramatic effects on both hyperglycemia and
hyperlipidemia.
30
Hypothyroidism
The classical manifestation of hypothyroidism is elevation of LDL-C, but it can
also cause elevation of plasma triglycerides. Levels of HDL-C are unchanged or slightly
lower. Hyperlipidemia with hypothyroidism responds dramatically to thyroid hormone
replacement. In patients with ischemic heart disease, rapid thyroxine replacement may
exacerbate the condition.
Estrogen Therapy
Estrogen therapy increases plasma triglyceride levels by increasing synthesis of
VLDL, occasionally causing marked hypertriglyceridemia, resulting in pancreatitis.
Estrogen therapy also enhances LDL clearance and reduces LDL-C levels. Estrogens also
increase HDL-C levels.
Alcohol Consumption
The regular consumption of large quantities of alcohol leads to increased
triglyceride synthesis, fatty liver, and enhanced VLDL synthesis, occasionally causing
massive hypertriglyceridemia and pancreatitis. Alcohol consumption is also associated
with higher plasma levels of HDL-C.
Nephrotic Syndrome
Total cholesterol, VLDL, LDL-C, triglycerides and plasma apo-B are all
elevated in patients with nephrotic syndrome. Plasma Lp(a) levels can also be elevated.
Hyperlipidemia is secondary to increased production of LDL and VLDL.
31
Protease inhibitors
Combination therapy with protease inhibitors for human immunodeficiency virus
infection is associated with hyperlipidemia, lipodystrophy and insulin resistance.
Other drugs
Other therapeutic agents causing hyperlipidemia include glucocorticoids, thiazide
diuretics and -adrenergic blockers. Exogenous androgens can reduce HDL-C levels.
32
c) Anaemia25
Definition26,27
Anaemia may be defined as a reduction below normal limits of the total red cell
mass. This value is not easily measurable and anaemia has been defined as a reduction
below normal of the haematocrit or a reduction in the haemoglobin concentration of the
blood. The World Health Organization28 recommends that anaemia should be considered
to exist in adults whose haemoglobin levels are lower than 13 g/dl (males) or 12 g/dl
(females).
Prevalence
Anaemia is a major world health problem. It is estimated to affect at least 20% of
the world population28. It is most common in women between the ages of 15 and 44
years, and the prevalence increases again in the elderly. The majority of cases are due to
iron deficiency. In India, 30% adult males, 45% adult females, 80% pregnant females and
60% children have iron deficiency29.
Adaptation to Anaemia30,31
Anaemia reduces the oxygen carrying capacity of blood and thereby reduces the
arteriovenous oxygen difference. This is compensated by three mechanisms:
1. Intrinsic red cell adaptation Increased 2,3-biphosphoglycerate (2,3-BPG)

concentration in the RBC shifts the oxygen dissociation curve to the right, significantly
enhancing tissue oxygen delivery by as much as 40%.
33
2. Local changes in tissue perfusion is achieved by shunting blood from less to

more vital organs, there is vasoconstriction of the blood vessels of the skin and kidney.
3. Cardiovascular changes When the haemoglobin level falls below 7 to 8 g/dl,

cardiac output increases with a raised stroke rate and hyperkinetic circulation.
Vasodilatation with reduced afterload and reduced viscosity of blood are responsible for
the high-output state in anaemia.
Clinical Manifestations26
Anaemia due to acute blood loss is characterized by shock, with collapse, dyspnoea,
tachycardia, feeble pulse, hypotension, and marked peripheral vasoconstriction32,33.
With chronic anaemias, the presentation is variable. Mild anaemia may be

asymptomatic or associated with easy fatigability and slight pallor. Further symptoms
appear with increasing severity of anaemia. Pallor is best observed in the mucous
membranes.
Cardio
respiratory
features34,35
include
exertional
dyspnoea,
tachycardia,
palpitations, angina or claudication, night cramps, increased arterial and capillary

pulsations, cardiac murmurs, cardiomegaly and features of congestive cardiac failure.
Neuromuscular manifestations include headache, vertigo, light-headedness, tinnitus and
muscle cramps.
Gastrointestinal symptoms include loss of appetite, nausea, constipation and

diarrhoea. Genitourinary involvement causes menstrual irregularities, urinary frequency,
34
and loss of libido. Previously undiagnosed coronary artery narrowing maybe unmasked
by the onset of angina.
Classification of Anaemias26
Anaemias maybe classified according to underlying mechanism or RBC
morphology.
Classification of Anaemias according to underlying mechanism27

I. Blood loss
1. Acute: Trauma
2. Chronic: GIT lesions, gynaecological diseases
II. Haemolytic Anaemias
1. Intrinsic abnormalities of RBCs
Intrinsic
a) RBC membrane disorders
Disorders of membrane cytoskeleton: spherocytosis, elliptocytosis
Disorders of lipid synthesis: selective increase in membrane lecithin
b) RBC enzyme deficiencies
Glycolytic enzymes: pyruvate kinase deficiency, hexokinase

deficiency
HMP shunt enzymes: G6PD, glutathione synthetase
c) Disorders of haemoglobin synthesis
Deficient globin synthesis: -thalassemias, -thalassemias
35
Haemoglobinopathies: sickle cell anaemia, haemoglobin D, unstable

haemoglobins
Acquired
a) Membrane defect: paroxysmal nocturnal haemoglobinuria
2) Extrinsic abnormalities
Antibody mediated
a) Isohaemagglutinins: transfusion reactions, erythroblastosis fetalis
b) Autoantibodies: idiopathic, drug-associated, systemic lupus
erythematosus, malignant neoplasms, mycoplasmal infection
Mechanical trauma to RBCs
a) Microangiopathic haemolytic anaemias: thrombotic thrombocytopenic
purpura, disseminated intravascular coagulation
b) Cardiac traumatic haemolytic anaemia
Infections: malaria
Chemical injury: lead poisoning
Sequestration in mononuclear phagocyte system: hypersplenism
III. Impaired RBC production
1) Disturbed proliferation and differentiation of stem cells: aplastic anaemia,
pure red cell aplasia, anaemia of renal failure, anaemia of endocrine disorders
2) Disturbance of proliferation and maturation of erythroblasts
Defective DNA synthesis: vitamin B12 and folate deficiency (megaloblastic
anaemia)
Defective haemoglobin synthesis
36
a) Defective heme synthesis: iron deficiency

b) Defective globin synthesis: thalassemias
Unknown mechanisms: sideroblastic anaemia, anaemia of chronic
infections, myelophthisic anaemias due to marrow infiltration
Classification of Anaemias according to RBC morphology

I. Hypochromic-microcytic (reduced MCV, MCH, and MCHC)
1) Genetic
Thalassemia
Sideroblastic anaemia
2) Acquired
Iron deficiency
Sideroblastic anaemia
Chronic disorders
II. Normocytic-macrocytic (increased MCV)
1) With megaloblastic marrow: vitamin B12 or folate deficiency
2) With normoblastic marrow: liver disease, myelodysplasia, chemotherapy
III. Polychromatophilic-macrocytic (increased MCV)
1) Haemolysis
IV. Normochromic-normocytic (normal indices)
1) Chronic disorders: Infection, malignancy, collagen disease, rheumatoid
arthritis
2) Renal failure
3) Hypothyroidism, hypopituitarism
37
4) Aplastic anaemia or primary red-cell hypoplasia

5) Primary disease of bone marrow: leukemia, myelosclerosis, malignant
infiltration
V. Leucoerythroblastic (indices usually normal)
1) Myelosclerosis
2) Leukemia
3) Metastatic carcinoma
General Principles in the Management of Anaemias26

The cause of anaemia should always be sought before treatment is started. Most
cases of iron deficiency anaemia require further investigation for blood loss. If there is
clear-cut history regarding the cause, iron therapy maybe started without further
investigations and haemoglobin levels monitored during and after therapy. A rise of
haemoglobin level of 1g/dl per week indicates a full response. For megaloblastic
anaemias, treatment with vitamin B12 and folic acid maybe started once blood samples
have been obtained for serum folate and B12 levels. A brisk reticulocyte response is
normally seen in 5 to 7 days.
Blood transfusion should be avoided unless the haemoglobin level is dangerously

low, in which the patient should be transfused up to a safe level and then the
haemoglobin should be allowed to return to normal following appropriate treatment of
cause.
38
Patients who present with severe congestive cardiac failure due to profound
anaemia require transfusing up to a safe level, i.e., a haemoglobin level of 6 to 8 g/dl.
This is done by transfusing two to three units of packed cells along with frusemide.
Patient should be monitored for fluid overload during the transfusion. In patients with
very severe failure, packed cells maybe transfused through one arm while removing an
equal amount of blood from the other.
Anaemias of Blood Loss

Acute Blood Loss27
The clinical and morphological response to blood loss depends on the rate of
haemorrhage and whether blood is lost internally or externally. Shock and death may
follow acute blood loss. If the patient survives, the blood volume is rapidly restored by
shift of water from interstitial fluid, resulting in lowering of haematocrit. Increased
erythropoetin secretion triggers increased erythropoesis. In case of internal haemorrhage,
iron can be recaptured, however, external blood loss may cause iron deficiency in the
presence of inadequate reserves. Reticulocytosis of up to 10 to 15% is seen after 7 days.
Chronic Blood Loss

Chronic blood loss induces anaemia only when the rate of loss exceeds the
regenerative capacity of the erythroid precursors or when iron reserves are depleted. It
usually causes iron deficiency anaemia. Common sites of chronic blood loss are the
gastrointestinal tract36,37 and female reproductive tract38.
39
Haemolytic Anaemias39
The haemolytic anaemias are characterized by the following features:
Premature destruction of RBCs
Accumulation of products of haemoglobin catabolism
Marked increase in erythropoesis
Haemolytic anaemias may be intravascular (within the vascular
compartment), or extravascular (within the mononuclear phagocyte system)
Intravascular haemolysis occurs when normal erythrocytes are damaged by

mechanical injury (mechanical cardiac valves or micro thrombi), complement fixation to
the red cells (mismatched blood transfusion), or exogenous toxic factors (falciparum
malaria and clostridium sepsis). It is manifested by haemoglobinemia, haemoglobinuria,
methemalbuminemia, unconjugated hyperbilirubinemia and haemosiderinuria. Serum
haptoglobulin level is decreased.
Extravascular haemolysis occurs when RBCs are injured, rendered foreign, or

become less deformable, leading to sequestration within the spleen, followed by
phagocytosis. Haemoglobinemia, haemoglobinuria and haemosiderinuria do not occur in
extravascular haemolysis. Plasma haptoglobin levels are usually reduced.
Haemolytic anaemias cause marked increase in marrow normoblasts and

extramedullary hematopoesis. Prominent reticulocytosis is a common feature. Pigment
gallstones are formed due to elevated levels of bilirubin. Haemosiderosis of the
mononuclear phagocytic system is seen in chronic cases.
40
Hereditary Spherocytosis40
Hereditary spherocytosis is an autosomal dominant disorder of the RBC membrane,
with defective spectrin, ankyrin or protein 3, the proteins providing the scaffolding for
RBC membranes. This results in loss of membrane with decreased surface to volume
ratio and a spherical shape with decreased deformability, causing trapping and
haemolysis of RBCs in the spleen.
The characteristic clinical features are anaemia, splenomegaly and jaundice. The
severity of the disease is variable. Aplastic crisis is due to temporary suppression of RBC
production, usually by parvovirus infection, manifested by sudden worsening of anaemia
and disappearance of reticulocytes from the blood. Gallstones may be found. Diagnosis is
based on family history, haematological findings and demonstrating the raised osmotic
fragility of RBCs. Most patients are benefited by splenectomy and folate
supplementation.
Hereditary Elliptocytosis40
Hereditary elliptocytosis is a genetically heterogeneous disorder characterized by
elliptical cells and haemolysis. Both autosomal dominant and autosomal recessive forms
have been identified. It is usually due to point mutations or deletions in the -spectrin or
-spectrin genes. It is characterized by anaemia, splenomegaly and reticulocytosis. The
peripheral smear contains elliptocytes and pencil cells. Management is similar to that of
hereditary spherocytosis.
41
Glucose-6-Phosphate Dehydrogenase Deficiency41

G6PD catalyses the first step in the HMP shunt, responsible for protecting cells
from oxidative damage. G6PD deficiency is an X-linked recessive disorder. Commonly
patients are usually asymptomatic, but may experience episodes of severe haemolysis and
anaemia during periods of oxidant stress, such as drugs (primaquine, sulfonamides,
sulfones, nitrofurans, analgesics, chloramphenicol etc), chemicals, infectious agents and
the bean Vicia faba (favism).
Intravascular haemolysis occurs within 24 hours of exposure with malaise and

abdominal pain. Anaemia, jaundice, haemoglobinuria and acute renal failure develop
within 2 to 3 days. Peripheral smear reveals anisocytosis, poikilocytosis and Heinz
bodies. Diagnosis depends on the demonstration of decreased red cell G6PD activity.
Management consists of avoidance of precipitating factors and blood transfusion.
Paroxysmal Nocturnal Haemoglobinuria

Paroxysmal nocturnal haemoglobinuria is an acquired clonal stem cell disorder due
to a mutation in the phophatidylinositol glycan A gene, resulting in abnormal sensitivity
of RBCs to lysis by complement.
Patients present with episodic haemoglobinuria in the morning urine since mild
respiratory acidosis of sleep leads to enhanced complement activity. Anaemia,
thrombosis of hepatic, portal or cerebral veins and iron deficiency are other features.
PNH may progress either to aplastic anaemia, myelodysplasia or acute myelogenous
leukemia.
42
Anaemia, haemosiderinuria, elevated serum LDH, iron deficiency, leucopenia,

thrombocytopenia, decreased leucocyte alkaline phophatase, and absence of CD59 by
flow cytometry are the findings on investigation. Treatment is with iron replacement,
prednisolone and allogenic bone marrow transplantation.
Autoimmune Haemolytic Anaemia

Autoimmune haemolytic anaemia is an acquired disorder in which autoantibodies
(IgG) are formed against the RBC membrane, resulting in haemolysis. It is usually
idiopathic, but may be also seen in association with systemic lupus erythematosus,
chronic lymphocytic leukemia, or lymphomas.
Autoimmune haemolytic anaemia produces anaemia of rapid onset, which may

present with angina or congestive cardiac failure. Jaundice and splenomegaly are present.
Investigations reveal anaemia of variable severity, reticulocytosis, coincident immune
thrombocytopenia (Evans syndrome) and positive direct Coombs test. Treatment is with
prednisolone, blood transfusion, rituximab, danazol, cyclophophamide, azathioprine,
cyclosporine and splenectomy.
Mechanical Trauma
Haemolytic anaemias may be associated with cardiac valve prosthesis and with
narrowing and obstruction of the vasculature. Microangiopathic haemolytic anaemia is
chaacterised by mechanical damage to RBCs as they squeeze through abnormally
narrowed vessels. It is commonly due to disseminated intravascular coagulation,
43
malignant hypertension, systemic lupus erythematosus, thrombotic thrombocytopenic

purpura, haemolytic uremic syndrome and disseminated cancer. Burr cells, helmet cells
and triangle cells may be seen in the peripheral blood film. It may cause iron deficiency
due to continuous low-grade haemoglobinuria.
Hypersplenism
In cases of splenomegaly, increased destruction of formed elements of the blood
takes place due to pooling of blood in the spleen. Patients with cytopenia sufficient to
cause symptoms benefit from splenomegaly.
Haemoglobinopathies42
Haemoglobinopathies are a heterogeneous group of conditions which may be either
inherited or acquired. They may be subdivided into 5 major classes
I.
Structural haemoglobinopathies
a. Abnormal polymerization HbS, haemoglobin sickling
b. Altered O2 affinity familial polycythemia, cyanosis, pseudoanaemia
c. Readily oxidized haemoglobin
II.
Thalassemias
a. Thalassemias
b. Thalassemias
c. , , Thalassemias
III.
Thalassemic haemoglobin variants

a. HbE
b. Hb Constant Spring
44
c. Hb Lepore
IV.
Hereditary persistence of fetal haemoglobin
V.
Acquired haemoglobinopathies
a. Methaemoglobin
b. Sulfhaemoglobin
c. Carboxyhaemoglobin
d. HbH in erythroleukemia
e. Elevated HbF in states of erythroid stress and bone marrow dysplasia
Sickle Cell Anaemia43

Sickle cell anaemia is an autosomal recessive disorder. A single DNA base change
leads to an amino acid substitution of valine for glutamine in the sixth position on the globin chain. When in the deoxy form, haemoglobin S forms polymers that damage the
RBC membrane, causing sickling.
Sickle cell anaemia produces jaundice, pigment gallstones, splenomegaly, and

poorly healing ulcers over the tibia. Anaemia may become life threatening due to
haemolytic or aplastic crisis. Acute painful episodes due to vaso-occlusion cause
infarction in a large number of organs.
Peripheral smear reveals sickled cells, reticulocytosis, nucleated RBCs, HowellJolly bodies and target cells. The diagnosis is confirmed by haemoglobin electrophoresis.
Treatment options include folate supplementation, blood transfusions, pneumococcal
45
vaccination, adequate hydration and oxygenation during acute painful episodes,

hydroxyurea, and allogenic bone marrow transplantation.
Thalassemias44
The thalassemias are hereditary disorders characterized by reduction in the
synthesis of globin chains, causing reduced haemoglobin synthesis and a microcytic,
hypochromic anaemia. Alpha thalassemia is due to gene deletion causing reduced globin chain synthesis. Beta thalassemias are usually caused by point mutations resulting
in reduced or absent -globin chain synthesis, resulting in a relative increase in HbA2 and
HbF. The excess alpha chains precipitate and damage RBC membranes, leading to
haemolysis.
Normal adults have four copies of the -globin gene. People with three functioning
-globin genes are silent carriers. When two -globin genes are present, the patient has
alpha thalassemia trait, with mild microcytic anaemia. When only one -globin gene is
present, the patient has Haemoglobin H disease, with chronic haemolytic anaemia, pallor
and splenomegaly. Patients may require blood transfusions during periods of haemolytic
exacerbation caused by infection or other stresses. When all four -globin genes are
deleted, the affected fetus is stillborn as a result of hydrops fetalis.
Patients homozygous for beta thalassemia have thalassemia major. Severe anaemia
develops at the age of 6 months, when haemoglobin synthesis switches from HbF to
HbA. It is characterized by growth failure, bony deformities, hepatosplenomegaly and
jaundice. Transfusion therapy can cause haemosiderosis with heart failure, cirrhosis and
46
endocrinopathies. Patients homozygous for a milder form of beta thalassemia have

thalassemia intermedia, with chronic haemolytic anaemia not requiring blood transfusion.
Patients heterozygous for beta thalassemia have thalassemia minor and a clinically
insignificant microcytic anaemia.
Laboratory findings include microcytic hypochromic anaemia, target cells,

poikilocytosis, reticulocytosis, basophilic stippling and nucleated RBCs. Haemoglobin
electrophoresis reveals the percentage distribution of the various haemoglobins.
Mild thalassemia requires no intervention except genetic counseling. Patients with

severe thalassemias require regular blood transfusions and folate supplementation with
iron chelation therapy. Splenectomy and allogenic bone marrow transplantation are other
options.
Anaemias of Impaired RBC Production

Aplastic Anaemia45,46
Aplastic anaemia results from failure or suppression of multipotent myeloid stem
cells, with inadequate production or release of the differentiated cell lines. It is
characterized by anaemia, neutropenia and thrombocytopenia. It may be acquired or
inherited.
Causes
I.
Acquired
a) Idiopathic Primary stem cell defect, Immune mediated
b) Chemical agents
47
i. Dose related Alkylating agents, antimetabolites, benzene,

chloramphenicol, Inorganic arsenicals
ii. Idiosyncratic Chloramphenicol, phenylbutazone, organic arsenicals,
methylphenylethylhydantoin, streptomycin, chlorpromazine, insecticides
c) Physical agents whole body irradiation
d) Viral infections Non-A, non-B hepatitis, cytomegalovirus, ebstein barr
virus, Herpes, varicella-zoster
e) Miscellaneous
II.
Inherited Fanconis anaemia
Aplastic anaemia may present at any age, onset is usually gradual. Symptoms are
due to decrease in all the three formed elements of blood. Bone marrow examination
reveals hypocellular marrow. Withdrawal of toxic drugs may lead to complete recovery.
Idiopathic form has poor prognosis. Therapy consists of antithymocyte globulin with
cyclosporine or allogenic bone marrow transplantation.
Pure Red Cell Aplasia47

Pure red cell aplasia is a rare form of marrow failure due to aplasia of erythroid
precursors. It may be primary, or secondary to thymoma or leukemia. Immunosuppresive
therapy, resection of thymic tumour, and plasmapheresis are the therapeutic options
Anaemia of Renal Failure48

Chronic renal failure of any etiology is invariably associated with anaemia
proportional to the severity of uremia. The anaemia of chronic renal failure is
48
multifactorial in origin. Chronic haemolysis results from an extracorpuscular defect.

Bleeding tendencies associated with uremia may cause iron deficiency. Reduced
erythropoietin synthesis causes reduced red cell production. Correction of iron deficiency
with administration of recombinant erythropoietin results in significant improvement of
anaemia.
Megaloblastic Anaemias49
Megaloblastic anaemias are a diverse group of entities, having in common impaired
DNA synthesis and distinctive morphologic changes in the blood and bone marrow. The
erythroid precursors and erythrocytes are abnormally large, due to defective cell
maturation and division.
The peripheral blood smear reveals normochromic anisocytosis. Macro-ovalocytes

are seen. Reticulocytes are reduced and nucleated RBCs may be seen. Neutrophils are
large and hypersegmented. The bone marrow is hypercellular and megaloblastic change
is seen in all stages of red cell development. The granulocytic precursors also reveal
nuclear-cytoplasmic asynchrony, with giant metamyelocytes and band forms and
hypersegmentation of neutrophils. Megakaryocytes are also abnormally large and have
bizarre, multilobate nuclei. Ineffective erythropoesis results from intramedullary
hemolysis.
49
Causes
I. Vitamin B12 deficiency
a) Decreased intake Inadequate diet, vegetarianism
b) Impaired absorption
i. Intrinsic factor deficiency Pernicious anaemia, gastrectomy
ii. Malabsorption states
iii. Diffuse intestinal disease lymphoma, systemic sclerosis
iv. Ileal resection, ileitis
v. Fish tapeworm infection
vi. Bacterial overgrowth in blind loops
c) Increased requirement pregnancy, hyperthyroidism, disseminated cancer
II. Folic acid deficiency
a) Decreased intake alcoholism, infancy
b) Impaired absorption malabsorption states, intrinsic intestinal disease,
anticonvulsants, oral contraceptives
c) Increased loss haemodialysis
d) Increased requirement pregnancy, infancy, disseminated cancer, increased
haematopoesis
e) Impaired use folic acid antagonists
III. Other causes
a) Metabolic inhibitors mercaptopurines, fluorouracil, cytosine
b) Unexplained disorders pyridoxine and thiamine responsive megaloblastic
anaemia, acute erythroleukemia
50
Pernicious anaemia50
Pernicious anaemia is due to immunologically mediated destruction of gastric
mucosa with diffuse chronic gastritis. Myelin degeneration of the dorsal and lateral tracts
of the spinal cord is seen.
Pernicious anaemia is insidious in onset, patient usually presents with marked

anaemia. Diagnostic features include megaloblastic anaemia, leucopenia with
hypersegmented granulocytes, thrombocytopenia, involvement of posterolateral spinal
tracts, achlorhydria, inability to absorb an oral dose of cobalamin, low serum levels of
vitamin B12, excretion of methylmelonic acid in urine, reticulocytosis and improvement
of anaemia after parenteral administration of vitamin B12.
Folic acid deficiency

Deficiency of folic acid results in a megaloblastic anaemia having the same
characteristics as vitamin B12 deficiency. However, the neurological changes seen in
vitamin B12 deficiency do not occur. The diagnosis of folate deficiency requires the
demonstration of decreased serum folate levels and increased urinary excretion of
formiminoglutamate (Figlu) after administration of histidine.
Iron Deficiency Anaemia51

Iron deficiency is the most common cause of anaemia. In general, iron metabolism
is balanced between absorption and loss of 1 mg/day. Only 10% of dietary iron is
absorbed.
51
Causes
I.
Deficient diet
II.
Decreased absorption
III. Increased requirement pregnancy, lactation

IV. Blood loss- gastrointestinal, menstrual, blood donation
V.
Haemoglobinuria
VI. Iron sequestration pulmonary haemosiderosis
Iron deficiency anaemia commonly presents with easy fatiguability, palpitations

and breathlessless. Severe deficiency causes skin and mucosal changes, including
glossitis, brittle nails, and cheilosis. Dysphagia may result due to formation of esophageal
webs (Plummer-Vinson syndrome). Patients may develop pica.
Iron deficiency develops in stages. The first is depletion of iron stores with low
serum ferritin levels and elevated serum total iron-binding capacity. In early stages, MCV
remains normal. Subsequently MCV falls and blood smear shows hypochromic
microcytic cells. With further progression, anisocytosis and poikilocytosis develop. In
severe iron deficiency, severely hypochromic cells, target cells, hypochromic pencilshaped cells and nucleated red blood cells are seen.
The most important part of treatment is identification of the cause, especially

gastrointestinal blood loss. Iron replacement maybe given orally or parenterally. An
appropriate response is return of the hematocrit level halfway toward normal within 3
52
weeks with full return to baseline after 2 months. Iron therapy should continue for 3-6
months after restoration of normal hematological values.
Sideroblastic Anaemia52
Sideroblastic anaemias are a heterogenous group of conditions in which
haemoglobin synthesis is reduced because of failure to incorporate heme into
protoporphyrin to form haemoglobin. Iron accumulates, particularly in the mitochondria.
Sideroblastic anaemias are usually acquired. It may be a transitional stage of
myelodysplasia, other causes are alcoholism and lead poisoning. Hereditary forms are
also seen. Investigations reveal moderate anaemia, normal MCV, dimorphic picture in the
peripheral smear, with marked erythroid hyperplasia and ringed sideroblasts in the
peripheral smear. Iron stores are increased. Treatment is with pyridoxine, blood
transfusions and iron chelation.
Anaemias of Chronic Disease53

Anaemia may be seen in various chronic diseases such as chronic microbial
infections (osteomyelitis, bacterial endocarditis, lung abscess), chronic immune disorders
(rheumatoid arthritis, regional enteritis), neoplasms (hodgkins disease, carcinomas of the
lung and breast) and alcoholism54. Common features are low serum iron and reduced total
iron-binding capacity in association with abundant stored iron in mononuclear phagocytic
cells, suggesting a defect in the recycling of iron. The principal cause for anaemia in this
setting is marrow hypoproliferation due to inadequate erythropoietin synthesis. Treatment
of the underlying condition corrects the anaemia, as does administration of recombinant
erythropoietin.
53
d) Anaemia and Hypocholesterolemia1

Few studies have examined the association and significance of hypocholesterolemia
related to anaemia. Since cholesterol level is a risk factor for arteriosclerosis and
coronary heart disease, it is important to evaluate the extent of the relationship between
cholesterol and haemoglobin levels in anaemic patients. The exact pathogenesis of
hypocholesterolemia in anaemic patients remains unknown.
Clinical Reports and Outcomes

Rifkind and Gale4,5 in 1967 showed that the decrease in serum cholesterol was not
due to a specific lowering of any of the serum lipoprotein families, and that
hypocholesterolemia was caused by a proportional reduction in all the major lipoprotein
families. The finding was compatible with a plasma volume-dependent effect.
Furthermore, the study indicated that splenectomy lead to a doubling of the cholesterol
value in a patient with microspherocytosis, and that vitamin B12 therapy in a patient with
pernicious anemia was associated with a rise in serum cholesterol.
In 1970, a study was conducted in 4,070 women6, of whom 124 were found to have
haemoglobin levels below 10.5 g/dl. In the women with haemoglobin levels 10.5g/dl,
the serum cholesterol levels were 241 2.5 mg/dl; in the women with haemoglobin
<10.5g/dl, the serum cholesterol levels were 211 3.9 mg/dl. The mean difference in
cholesterol between women with haemoglobin levels above and below 10.5g/dl was
found to be significant (30 mg/dl).
54
The women with haemoglobin levels < 10.5g/dl were admitted to a clinical trial in
which they received 0, 30 or 90 mg iron daily for 12 weeks. Anaemia treatment led to a
rise in serum cholesterol. The simplest explanation for the observed relation between
haemoglobin and cholesterol levels was a dilution effect (the increased volume of serum
in anaemia carrying the same total load of cholesterol). This hypothesis was attractive,
particularly as the difference in packed-cell volume between the groups in the study was
proportionally similar to the difference in cholesterol levels.
A study by Westerman7 examined the relationship between hypocholesterolemia

and various types of anaemia, including megaloblastic anaemia, hereditary spherocytosis,
homozygous sickle cell disease, aplastic anaemia, and liver associated anaemia. After
B12 or folic acid therapy, there was a parallel increase in haematocrit and cholesterol in
patients with megaloblastic anaemia. After splenectomy plasma cholesterol and
haematocrit increased in patients with hereditary spherocytosis. The haematocrit and
plasma cholesterol levels in patients with sickle cell disease were low before treatment
and increased after transfusion. As the haematocrit increased, so did the cholesterol levels
after treatment. Haematocrit and cholesterol levels also increased in a patient with
aplastic anaemia after transfusion.
The study showed that the plasma cholesterol level is closely related to haematocrit
levels, both initially and throughout the course of the anaemias associated with
hypocholesterolemia. This association was maintained regardless of the cause of changes
in haematocrit levels. The authors concluded that low haematocrit, not the type of
anaemia, is the cause of low cholesterol levels. The authors pointed out that the
55
haematocrit-cholesterol association appeared more likely to be related to changes in

cholesterol distribution or plasma dilution, because of the rapidity with which the
cholesterol change occurred after transfusion, and the close relationship between
haematocrit and cholesterol levels in the uncomplicated anaemias.
A study by El-Hazmi55 et al supports the theory of plasma dilution. This study

investigated plasma levels of cholesterol and triglycerides in 45 patients with sickle cell
anaemia (HbSS) and 45 age- and sex-matched controls with normal haemoglobin
(HbAA). The levels of haemoglobin and plasma cholesterol were significantly lower in
the patients with sickle cell anaemia than in normal controls. However, the triglyceride
level did not vary significantly between the two groups. The authors concluded that
hypocholesterolemia in sickle cell disease may be due to an idiopathic decrease in the
endogenous production of cholesterol, increased utilization of cholesterol, liver function
abnormalities, or an increase in the plasma volume.
In contrast to the previously mentioned studies, Seip and Skrede56 considered

haemodilution only a part of the explanation for the lower cholesterol levels found in
anaemic individuals, since the decrease in cholesterol level is more significant compared
to the decrease in haematocrit level. The patient population consisted of 17 children, 9
with hemolytic anaemias, 3 with congenital hypoplastic anaemia, 2 with congenital
sideroblastic anaemia, and 2 with iron deficiency anaemia. All patients with anaemia had
low levels of cholesterol and an association was found between serum cholesterol and
haemoglobin in all 17 patients, but no clear association was found between triglyceride
and haemoglobin levels. The study showed that hypocholesterolemia also accompanied
56
hypoplastic and aplastic anaemia. There was no difference in cholesterol levels between
hemolytic anaemias with very active erythropoiesis and anaemias with low erythropoietic
activity. Cholesterol levels increased after treatment in patients with hemolytic or aplastic
anaemia.
A study conducted by Dessi57 et al in children with glucose-6-phosphate

dehydrogenase (G6PD) deficiency during haemolytic anemia induced by fava bean
ingestion showed that total cholesterol, low-density lipoprotein (LDL), and high-density
lipoprotein (HDL) cholesterol levels were reduced, and those reductions were found in
association with maximal bone marrow hyperplasia. It was concluded that these changes
in cholesterol concentrations were due to an increased utilization of cholesterol by
proliferating cells.
The same conclusion was drawn by El-Hazmi58 et al, who investigated 400 normal
individuals, 100 patients with sickle cell disease (HbSS), 220 sickle heterozygotes
(HbAS), and 100 patients with G6PD deficiency. Sickle cell patients had significantly
lower cholesterol compared to the normal individuals, whereas no significant differences
were found between the HbAS and G6PD deficient groups. Analysis showed a
statistically significant positive correlation between plasma cholesterol and total
hemoglobin in each group, particularly the HbSS group. The results suggested that
increased utilization or decreased production might account for the lower cholesterol
levels in severely anaemic patients. In support of this finding are the results of a study
conducted by Akinyanju and Akinyanju59 who showed that subjects with sickle cell
disease had lower total cholesterol levels than normal subjects.
57
In 1986, Au60 et al suggested that decreased endogenous cholesterol synthesis by

the liver, possibly due to increased shunting of substrates required for the nonsterol
pathway, is the cause of hypocholesterolemia in anaemic patients. The investigators
studied the relationship between anaemia and hypocholesterolemia in an animal model
(sex-linked anemic mouse) characterized by iron deficiency anaemia, and found that
cholesterol levels were lower in anaemic mice than in non anaemic mice.
A study conducted by Choi61 et al showed that lipid levels in patients with iron
deficiency anaemia were directly related to the level of iron. The authors assigned
patients with blood haemoglobin of < 8.0g/dl to the severely anaemic group and
compared their serum lipid levels with those of patients with haemoglobin levels >
14.0g/dl. The total cholesterol level in the severely anaemic group was significantly
lower than that found in the other group (148 16 mg/dl versus 170 17mg/dl). The
triglyceride level was twofold higher in subjects with haemoglobin > 14.0g/dl than in
subjects with haemoglobin < 8.0g/dl. The serum lipid concentrations in the females with
severe anaemia were significantly higher after iron supplementation. Overall, the study
showed that blood haemoglobin levels correlated significantly with serum cholesterol
concentrations.
The results of the above study were contradicted by a study done by Tanzer62 et al,
which aimed to determine the effect of iron deficiency on lipid metabolism. The study
group consisted of 70 children suffering from iron deficiency anaemia and 20 healthy
58
children. The results of the study indicated higher serum total triglyceride, total
cholesterol, and VLDL levels in iron deficient patients than in healthy controls.
The use of human granulocyte-macrophage colony stimulating factors (GM-CSF) to

improve haematopoiesis in patients with moderate to severe aplastic anaemia was
evaluated in a study by Nimer63 et al. The study group comprised eight patients. Serum
cholesterol levels decreased by 27% to 53% from baseline values in all but one patient.
A study conducted by Vitols64 et al in patients with acute myeloblastic anaemia

showed that the patients with both a high LDL-receptor activity per cell and a high white
blood cell count had the lowest cholesterol concentrations. Fifty nine patients with acute
leukemia were enrolled. The study showed that the high receptor-mediated uptake and
degradation of LDL by leukemic cells causes hypocholesterolemia in patients with acute
leukemia. Based on their results, the authors proposed that hypocholesterolemia in
leukemia and other neoplastic disorders might be due to elevated LDL-receptor activity
in the malignant cells.
Juliusson65 et al analyzed the role of LDL-receptor activity in patients with hairy

cell leukemia (HCL). Sixty-six symptomatic patients were enrolled. All patients were
treated with cladribine for 7 days. After successful cladribine therapy, LDL and HDL
cholesterol levels rose significantly, whereas triglyceride levels did not. The authors
concluded that the hypocholesterolemia in HCL is caused by a different mechanism than
in acute myeloid leukemia. Since the patients with splenomegaly had lower levels of
59
lipids, hypocholesterolemia was thought to be due to the large spleen size and not to
increased LDL receptor activity.
Gilbert and Ginsberg66 conducted a study in the patients with myeloproliferative

disease (MPD). The study group comprised 23 patients with polycythemia vera and 9
with agnogenic myeloid metaplasia. Significantly lower values of total plasma
cholesterol, LDL cholesterol and HDL cholesterol were observed. The removal rate of
LDL cholesterol was significantly increased in MPD patients compared to controls. The
authors noted that LDL might be removed from plasma by both nonspecific, low-affinity
processes such as fluid endocytosis and specific, high-affinity interactions with cell
surface receptors.
Deiana67 et al attempted to determine the influence of (0)-thalassemia on the

phenotypic expression of heterozygous familial hypercholesterolemia (FH). The study
was conducted in the Sardinian population. The study compared the cholesterol levels in
subjects with FH and (0)-thalassemia trait to those with FH but not the (0)-thalassemia
trait. Total and LDL cholesterol levels were significantly lower in subjects with
heterozygous FH and (0)-thalassemia trait than in subjects with heterozygous FH but
without (0)- thalassemia trait. There were no significant differences in HDL cholesterol
and triglyceride levels. Two mechanisms were proposed. First, anaemia induces the
secretion of erythropoietin, which stimulates erythroid hyperplasia with increase in the
expression of the LDL receptor. The second mechanism may be related to the activation
of the monocyte/macrophage system associated with increased release of some cytokines.
60
Pathophysiology
In general, five possibilities exist for hypocholesterolemia: decreased absorption,
decreased synthesis, increased excretion, shift of plasma cholesterol into other tissues, or
some combination of these factors. Dietary intake and altered absorption are unlikely
causes of hypocholesterolemia in the previously mentioned studies.
The Gilbert and Ginsberg66 study showed that LDL removal from plasma via fluid
endocytosis was the only reason for reduced LDL cholesterol levels in patients with
MPD. The high receptor-mediated uptake and degradation of LDL by leukemic cells was
the cause of hypocholesterolemia in patients with acute leukemia. On the other hand,
Juliusson65 et al proved there was no increased LDL receptor activity in hairy cells in
patients with HCL. In the patients with MPD66,68,69, spleen and liver size were found to be
significantly and inversely related to plasma concentrations of total, LDL, and HDL
cholesterol; it was suggested that the mechanism involved macrophages. Deiana67 et al
proposed that the action of the monocyte/macrophage system through the release of
cytokines is one mechanisms of reducing plasma cholesterol levels. Splenectomy results
in increased plasma cholesterol levels and in the elevation of serum cholesterol level in
diseases associated with hypersplenism4,7.
Relative decreased oxygenation of blood is a common characteristic in various

types of anaemia. Decreased oxygenation of blood in anaemia might affect lipid
absorption, transport, and synthesis70. Low oxygenation coupled with spontaneous
oxygen radical production, with increased catabolism of modified lipoproteins by
macrophage scavenger receptors, may also contribute to hypocholesterolemia in anaemic
61
patients. Some of the studies relating hypocholesterolemia and anaemia are limited to
those types of anaemia where an increased level of erythropoietin is present. Therefore,
hypocholesterolemia could be considered an indirect result of erythropoietin treatment.
However, Mat71 et al concluded that long-term treatment with recombinant human
erythropoietin does not significantly change lipid blood values in haemodialysis patients.
A compensatory increased erythrocyte production, along with increased utilization

of plasma lipids for the synthesis of erythrocyte membranes, could also contribute to
hypocholesterolemia72. Furthermore, possible increased use of cholesterol by newly
proliferated cells may result in a diminished supply of cholesterol for transport by
lipoproteins. Therefore, haemolysis in various anaemias can lead to increased turnover of
plasma total cholesterol with a consequent decrease in plasma content73.
Another contributing factor may be that the abnormalities in cholesterol levels are
related to the effect of plasma dilution, since in most anaemic states the plasma volume is
increased due to a reduction in the haematocrit6,74. A shortcoming of this theory is that
the rise in cholesterol level that follows treatment of anaemia is the not of the same
relative size as the observed rise in haematocrit. Therefore, a change in serum cholesterol
may not be a true reflection of the absolute change in total body cholesterol.
Other factors must also contribute to changes in the serum cholesterol, since
cholesterol levels do not always return to normal in patients whose anaemia is treated
with transfusion. These factors can include modest liver disease that might change
62
hepatic cholesterol synthesis and absorption7. It is not known how iron supplementation
in patients with iron deficiency anaemia increases cholesterol levels61.
Conclusion
Patients with anaemia may also have relative hypocholesterolemia, which is present
regardless of the cause of anaemia7, and correction of anaemia leads to a rise in serum
cholesterol levels. Serum cholesterol is closely related to the haematocrit level. There is
also a positive relation between cholesterol and haemoglobin75,76. Various investigators
have suggested that the patients with anaemia may have a lower risk of developing
ischemic heart disease compared with subjects with normal haemoglobin levels. This
may be due not only to the lower cholesterol levels seen in patients with anaemia, but
also due to iron induced free radical damage to the heart in patients with adequate iron
reserves. Rifkind and Gale4,5 suggested that anaemia may explain the differences in the
incidence of ischemic heart disease between the sexes, between premenopausal and
postmenopausal women, and between developed and underdeveloped countries.
However, none of these studies provide any data regarding the incidence of coronary
artery disease in patients with anaemia. Prospective cohort studies are needed in which
the development of coronary artery disease over time is compared in patients with
anaemia and controls.
Many studies have shown that serum cholesterol levels are reduced in anaemic
patients. However, few studies have been designed to understand the basis of this
phenomenon. Altered intake of absorption, abnormal synthesis, and altered excretion,
dilution, and redistribution are some of the mechanisms suggested to produce changes in
63
serum cholesterol levels. Further studies that are based on a greater number of cases of
anemia with various etiologies and that include measurements of specific lipoprotein
families (HDL, LDL, VLDL) are needed. To delineate some of the contributing factors
responsible, concurrent measurements of haematocrit and total cholesterol, including the
specific lipoprotein family, are also necessary. Furthermore, the rates of production and
degradation of VLDL and LDL in anaemic patients should be determined, since LDL
receptor activity in patients with anaemia may be inversely correlated with plasma
cholesterol concentration, as is the case in patients with acute leukemia64. Till date, only
the study conducted by Ginsberg and Gilbert has made this determination68,69. The
finding that splenectomy was associated with an increase in cholesterol levels indicates
that more studies are needed to clarify the role of LDL receptor-mediated removal from
plasma by macrophages. Finally, studies must follow-up patients to understand the true
effect of anaemia on cholesterol after a specific treatment.
64
4. Methodology
This is a study which has been carried out in the Department of Medicine,
Kempegowda Institute of Medical Sciences, Bangalore.
Source of Data
The data for this study was collected from patients who presented to Kempegowda
Institute of Medical Sciences, Bangalore, either on inpatient or outpatient basis.
Sample Size
100 cases, 100 controls
Study duration
June 2003 to June 2005
Inclusion Criteria
All proven cases of anaemia. Men: Hb < 13 gm%, Women: Hb < 12 gm%.
Exclusion Criteria
1. Children below 14 years
2. Obesity/Overweight: BMI > 25 kg/m2
3. Malnutrition: BMI < 19 kg/m2 or Serum Total Protein < 6 gm/dl or Serum
Albumin < 3.5/dl
4. Known case of Diabetes Mellitus or RBS > 200mg/dl or FBS > 126 mg/dl or
PPBS > 200 mg/dl
65
5. Known Hypertensives or Blood Pressure persistently more than 140/90 mm of Hg

on three consecutive readings taken on different days.
6. Alcoholics
7. Smokers
8. Known case of AIDS.
9. Known case of Ischaemic Heart Disease/ Cerebrovascular Accident.
10. History of recent blood loss.
11. History of use of steroids, oral contraceptives, diuretics, beta-blockers.
12. Urine Albumin +
13. Blood Urea > 40 mg% or Serum Creatinine > 1.4 mg%
14. SGOT > 40 U/L or SGPT > 40 U/L or Serum Alkaline Phosphatase > 250 U/L
15. TSH > 7.0 U/ml or TSH < 0.3 U/ml
Clinical evaluation
A detailed history was obtained from the subjects of the study, with special
emphasis on age, sex and occupation; non specific symptoms of anaemia like fatigability,
dyspnoea, giddiness, palpitations and angina; symptoms suggestive of a specific cause for
anaemia like pica, dysphagia, abdominal pain pain, bony pain, fever, loss of appetite,
weight loss, jaundice, bleeding, malaena, haemoglobinuria, menorrhagia, pregnancy and
post menopausal bleeding. Past history of disorders associated with dyslipidemia or
anaemia was obtained, including diabetes mellitus, hypertension, ischemic heart disease,
cerebrovascular accident, AIDS, recent blood loss and gall stones. Dietary habits and
habits like alcoholism and tobacco smoking was ascertained. History of intake of drugs
affecting lipid levels, such as oral contraceptives, beta blockers, diuretics, steroids and
66
NSAIDs was obtained. Family history of anaemia, jaundice and gallstones was also
obtained.
Each patient was subjected to a detailed general physical examination, with special
emphasis on pallor, koilonychias, icterus, pedal edema, lymphadenopathy, glossitis,
angular stomatitis, petechiae, haemolytic facies, ankle ulcers, perioral pigmentation and
knuckle pigmentation. Pulse, blood pressure, weight, height and body mass index was
measured.
Thorough systematic examination was made of the cardiovascular system to look

for the presence of elevated JVP, venous hum, cardiomegaly, S3 and flow murmur. The
respiratory system was examined to look for evidence of pulmonary oedema. Abdomen
was examined to look for organomegaly. The central nervous system was examined for
confusion, muscular weakness, deep tendon reflexes, vibration sense, position sense and
rombergs sign.
Investigations
Venous blood was drawn for investigations like complete haemogram, random
blood sugar, blood urea, serum creatinine, liver function tests, and thyroid stimulating
hormone levels. A urine sample was obtained for urine analysis, including albumin, sugar
and microscopy. Fasting venous blood sample (> 12 hours) was obtained for estimation
of lipid profile. T3 and T4 levels, fasting and post prandial (two hours after an oral dose of
75gms of glucose) blood sugar levels, and bone marrow aspiration cytology was done in
selected cases based on clinical assessment.
67
Complete haemogram was performed using the Sysmax automated analyzer.

Haemoglobin levels were confirmed by the colorimetric method. Differential count and
peripheral smear was done manually using Leishmanns stain by a qualified pathologist.
Urine albumin and sugar was estimated by dipstick method. Urine microscopy was done
manually by a qualified pathologist. Biochemical analyses were done using the fully
automated Technicon RA-XT system by Bayer. TSH, T4 and T3 were estimated using the
chemiluminescence method on the fully automated ADVIA Centaur system by Bayer.
Estimation of total cholesterol, HDL and triglycerides was done with the
commercially available Autopak cholesterol kit on Technicon RA-XT system. VLDL
was calculated using the formula, VLDL = Triglyceride/5. LDL cholesterol was
calculated using the Friedewalds equation. LDL = Total cholesterol [(Triglycerides/5)
+ HDL] mg/dl.
Controls
One hundred non anemic age and sex matched subjects were selected and screened
for compliance with the exclusion criteria. Complete haemogram, lipid profile and other
investigations were performed on them.
Statistical Methods80,81
Student t test has been used to test the homogeneity of age between case and
control. Chi-square test has been used to find the homogeneity of sex between case and
control. Student t test has been used to find the significance of Lipid profiles between
68
case and controls. Analysis of Variance has been used to find the significance of mean
lipid profiles when there are more than 2 groups. Mann Whitney U test has been carried
to find the significance between case and control for TC/HDL and LDL/HDL ratio.
Kruskal Wallis test has been used to find significance of TC/HDL and LDL/HDL ratio
when there are more than 2 groups. Effect Size due to Cohen d has been computed to find
the extent of effect of anemia on Lipid profiles.
0 < d < 0.20
No effect
0.20 < d < 0.50
Mild Effect
0.50 < d < 0.80
Moderate effect
0.80 < d < 1.20
Large effect
d > 1.20
Very Large effect
Statistical software
The statistical software used for the analysis of the data was SPSS 11.0 and Systat
8.0. Microsoft Word and Excel have been used to generate figures and tables.
69
5. Results
Study Design
A case - control study consisting of 100 anaemic cases and 100 normal subjects was
undertaken to study the clinical presentation of anaemic cases and also to investigate the
relationship between anaemia and lipid profile.
Age
The cases and controls were matched for age. Majority of the cases were middle
aged (30-60). The youngest case was 14 years old. The oldest was 75 years old.
Table 1
Age distribution with Haemoglobin levels in cases and controls
Case
Haemoglobin levels (in gm/dl)
Control
Age in years
(n=100)
<6
6-9
>9
Total
(n=23)
(n=40)
(n=37)
(n=100)
3
3
2
8
8
20
(13.0)
(7.5)
(5.40)
6
10
3
21-30
19
19
(26.1)
(25.0)
(8.1)
4
11
7
31-40
22
22
(17.4)
(27.5)
(18.9)
4
6
3
41-50
13
13
(17.4)
(15.0)
(8.1)
2
4
17
51-60
23
23
(8.7)
(10.0)
(45.9)
3
5
3
61-70
11
11
(13.0)
(12.5)
(8.1)
1
1
2
>70
4
4
(4.3)
(2.5)
(5.4)
Samples are age matched (P>0.05). Anaemic cases < 50 years
of age are 2.42 times more likely to have Hb levels < 6 gm/dl
Inference
(p=0.107) and Anaemic cases > 50 years of age are 4.31 times
more likely to have > 9 Hb gm/dl (P<0.01)
Figures in parenthesis are percentages
70
Figure 1
Age distribution in cases and controls
Age distribution (in years)
25
Case
15
Control
10
0
</=20
21-30
31-40
41-50
51-60
61-70
>70
Figure 2
Age and Severity of Anaemia
Age and Hb level

25
20
No of Cases
Percentages
20
15
Hb > 9 gm/dl
10
Hb 6-9 gm/dl
Hb < 6 gm/dl
5
0
< 21 21-30 31-40 41-50 51-60 61-70 >70
Age (in years)
71
Sex
The cases and controls were matched for sex. The cases consisted of 48 males and
52 females. Sex was not associated with haemoglobin levels.
Table 2
Sex distribution between case and controls
Case
Haemoglobin levels(in gm/dl)
Control
(n=100)
<6
6-9
>9
Total
(n=23)
(n=40)
(n=37)
(n=100)
10
19
19
48
48
(43.5)
(47.5)
(51.4)
13
21
18
52
52
(56.5)
(52.5)
(48.6)
Samples are sex matched (P>0.05). Sex is not statistically
associated with haemoglobin levels (P>0.05)
Sex
Male
Female
Inference
Figure 3
Sex distribution in cases and controls
Female
52%
Female
52%
Male
48%
Male
48%
Control
Case
72
Distribution of cases according to type and severity of Anaemia

A total of 100 cases were included in this study. 40 cases had dimorphic anaemia
(DM) according to peripheral smear, 25 cases had microcytic hypochromic anaemia
(MH), 18 cases had normocytic hypochromic anaemia (NH) and 10 cases had a
normocytic normochromic blood picture (NN). Out of the 7 cases grouped together as
others for the purpose of analysis, 3 cases had megaloblastic anaemia, 2 cases had
pancytopenia, and one case each had chronic myeloid leukemia and leukoerythroblastic
blood picture. A total of 23 cases had haemoglobin less than 6 gm/dl, 40 cases had
haemoglobin between 6 and 9 gm/dl, and 37 cases had haemoglobin more than 9 gm/dl.
Table 3
Distribution of cases according to type and severity of Anaemia
Type of Anaemia
Hb (in
gm/dl)
DM
MH
NH
NN
Others
Total
<6
14
23
6-9
21
15
40
>9
16
10
37
Total
40
25
18
10
100
73
Symptoms
The most common presenting symptom was easy fatigability, which was present in
51 cases. The next common symptoms were dyspnoea (29 cases), palpitations (27 cases)
and giddiness (24 cases). Other symptoms were loss of appetite (9 cases), fever (7 cases),
weight loss (5 cases), angina, dysphagia, jaundice and menorrhagia (3 cases each), bony
pain and bleeding (1 case) each. Not seen in the study group were pica, abdominal pain,
malaena, haemoglobinuria and pregnancy.
Figure 4
Symptoms
60
No of cases
50
A: Fatigue
B: Dyspnoea
C: Giddiness
D: Palpitations
E: Angina
F: Dysphagia
G: Bony pain
H: Fever
I : Loss of appetite
J: Weight loss
K: Jaundice
L: Bleeding
M: Menorrhagia
40
30
20
10
0
A
Symptoms
74
Symptoms and severity of anaemia

Cases with more severe anaemia were found to be more likely to have symptoms.
All cases with haemoglobin less than 6 gm/dl had at least one symptom, while out of 39
cases with haemoglobin more than 9 gm/dl, only 12 cases (30.8%) had at least one
symptom. Most symptoms were found more frequently in cases with more severe
anaemia. 100 % of cases with haemoglobin less than 6 gm/dl complained of fatigue,
compared to just 13.5 % of cases with haemoglobin more than 9 gm/dl. Fever, bony pain
and bleeding were the only symptoms which were found more frequently in cases with
less severe anaemia. Cases with severe anaemia also had more number of symptoms.
Cases with haemoglobin less than 6 gm/dl had an average of 3.7 symptoms, compared to
cases with haemoglobin more than 9 gm/dl, who had only an average of 0.6 symptoms.
Symptoms and type of anaemia

Non specific symptoms such as fatigue, dyspnoea, giddiness, palpitations, fever,
loss of appetite and loss of weight were equally frequent in the different types of
anaemia, except normocytic hypochromic anaemia and cases with normocytic
normochromic blood picture. This is possibly due to the fact that these cases had less
severe anaemia. Symptoms like angina, dysphagia and menorrhagia were seen only in
patients with dimorphic anaemia and microcytic hypochromic anaemia. Bony pain and
bleeding was seen only in one patient with chronic myeloid leukemia.
75
Table 4
Symptoms and severity of Anaemia
Presenting
Haemoglobin levels in cases (in gm/dl)
Illness
Total
<6
6-9
>9
(n=100)
(n=23)
(n=40)
(n=37)
23
23
5
Fatigue
51
(100.0)
(57.5)
(13.5)
19
10
Dyspnoea
29
(82.6)
(25.0)
10
11
3
Giddiness
24
(43.5)
(27.5)
(8.1)
14
9
4
Palpitation
27
(60.9)
(22.5)
(10.8)
3
Angina
3
(13.0)
Pica
3
Dysphagia
3
(13.0)
Abd pain
1
Bony pain
1
(2.7)
1
2
4
Fever
7
(4.3)
(5.0)
(10.8)
4
2
3
Loss of appetite
9
(17.4)
(5.0)
(8.1)
4
1
Wt loss
5
(17.4)
(2.5)
2
1
Jaundice
3
(8.7)
(2.5)
1
Bleeding
1
(2.7)
Malaena
Haemoglobinuria
2
1
Menorrhagia
3
(8.7)
(2.5)
Pregnancy
Post menopausal
bleed
76
Symptoms
Fatigue
Dyspnoea
Giddiness
Palpitation
Angina
Table 5
Symptoms and type of Anaemia
Types of Anaemia
DM
MH
NH
NN
(n=40)
(n=25)
(n=18)
(n=10)
31
14
1
(77.5)
(56.0)
(5.6)
15
9
1
(37.5)
(36.0)
(5.6)
13
6
2
1
(32.5)
(24.0)
(11.1)
(10.0)
14
8
3
(35.0)
(32.0)
(16.7)
2
1
(5.0)
(4.0)
Others
(n=7)
5
(71.4)
4
(57.1)
2
(28.6)
2
(28.6)
-
Pica
Dysphagia
1
(2.5)
2
(8.0)
Abd pain
Bony pain
1
(2.5)
3
(7.5)
1
(2.5)
1
(2.5)
2
(8.0)
2
(8.0)
3
(12.0)
1
(4.0)
2
(11.1)
2
(11.1)
1
(10.0)
Bleeding
Malaena
Haemoglobinuria
Menorrhagia
2
(5.0)
1
(4.0)
Pregnancy
Post menopausal
bleed
Fever
Loss of appetite
Wt loss
Jaundice
77
1
(14.3)
1
(14.3)
2
(28.6)
1
(14.3)
1
(14.3)
1
(14.3)
Past history
None of the cases was a known case of diabetes mellitus, hypertension, ischaemic
heart disease or AIDS. None of the cases had a past history of cerebrovascular accident,
recent blood loss or gall stones.
Personal history
19 cases were vegetarian. 34.8% (8 cases out of 23) of all cases with haemoglobin
less than 6 gm/ dl were vegetarian, compared to 15.8% (6 cases out of 38) of all cases
with haemoglobin more than 9 gm/ dl. Vegetarians were more likely to have dimorphic
anaemia (55.6%) compared to the other types of anaemia (5.6% to 22.2%). None of the
cases had a history of alcohol use or tobacco smoking.
Drug History
None of the cases had a history of intake of oral contraceptives, beta blockers,
diuretics, steroids or non steroidal anti inflammatory drugs.
Family history
Four cases had a family history of anaemia, out of whom three had microcytic
hypochromic anaemia. Five cases had a family history of jaundice, out of whom four had
dimorphic anaemia.
78

The most common finding on general physical examination was pallor, which was
present in 67 cases. Also seen were glossitis (20 cases), koilonychia (11 cases), angular
stomatitis (9 cases), knuckle pigmentation (7 cases), pedal oedema (6 cases), icterus (3
cases), lymphadenopathy (1 case) and perioral pigmentation (1 case). None of the cases
had petechiae, haemolytic facies or ankle ulcers.
Figure 5
70
60
A: Pallor
B: Koilonychia
C: Icterus
D: Pedal oedema
E: Lymphadenopathy
F: Glossitis
G: Angular stomatitis
H: Petechiae
I : Haemolytic facies
J: Ankle ulcers
K: Perioral pigmentation
L: Knuckle pigmentation
No of cases
50
40
30
20
10
0
A
79
General physical examination and severity of anaemia

Cases with more severe anaemia were found to be more likely to have findings on
general physical examination. All cases with haemoglobin less than 6 gm/dl had at least
one sign, while out of 39 cases with haemoglobin more than 9 gm/dl, only 8 cases
(21.6%) had at least one sign. All signs were found more frequently in cases with more
severe anaemia. 100 % of cases with haemoglobin less than 6 gm/dl had pallor and
56.5% had glossitis, compared to just 21.6 % and 0% in cases with haemoglobin more
than 9 gm/dl. Cases with severe anaemia also had more number of signs on general
physical examination. Cases with haemoglobin less than 6 gm/dl had an average of 2.8
signs, compared to cases with haemoglobin more than 9 gm/dl, who had only an average
of 0.2 signs.
General physical examination and type of anaemia

Pallor was equally frequent in the different types of anaemia, except normocytic
hypochromic anaemia and cases with normocytic normochromic blood picture. This is
possibly due to the fact that these cases had less severe anaemia. Koilonychia,
lymphadenopathy, glossitis and angular stomatitis were seen only in cases with
dimorphic anaemia and microcytic hypochromic anaemia. Knuckle pigmentation and
preioral pigmentation was seen only in cases with megaloblastic anaemia and dimorphic
anaemia.
80
Table 6
GPE and severity of Anaemia
GPE
Total
(n=100)
Pallor
67
Koilonychia
11
Icterus
Pedal oedema
Lymphadenopathy
Glossitis
20
Angular stomatitis
Petechiae
<6
(n=23)
23
(100.0)
9
(39.1)
2
(8.7)
6
(26.1)
6-9
(n=40)
36
(90.0)
2
(5.0)
1
(2.5)
>9
(n=37)
8
(21.6)
13
(56.5)
7
(30.4)
1
(2.5)
7
(17.5)
2
(5.0)
Haemolytis facies
Ankle ulcers
5
(21.7)
Peri oral
pigmentation
Knuckle
pigmentation
81
1
(2.5)
2
(5.0)
Table 7
GPE and type of Anaemia
Types of Anaemia
Symptoms
Pallor
Koilonychia
Icterus
Pedal oedema
DM
(n=40)
37
(92.5)
5
(12.5)
1
(2.5)
4
(10.0)
MH
(n=25)
20
(80.0)
6
(24.0)
1
(4.0)
NH
(n=18)
3
(16.7)
NN
(n=10)
Others
(n=7)
7
(100.0)
1
(14.3)
2
(28.6)
12
(30.0)
4
(10.0)
1
(4.0)
8
(32.0)
5
(20.0)
Petechiae
Haemolytis facies
Ankle ulcers
5
(12.5)
Lymphadenopathy
Glossitis
Angular stomatitis
Peri oral
pigmentation
Knuckle
pigmentation
82
1
(14.3)
2
(28.6)
Pulse Rate
The mean pulse rate was 85.4/ minute in cases and 83.7/ minute in controls. The
mean pulse rate was significantly increased (89.3/ minute) in cases with haemoglobin less
than 6 gm/dl. There was no difference in mean pulse rate between the different types of
anaemia except in the others group, in whom in was significantly raised (96.3/ minute).
Blood Pressure
The mean blood pressure was 121.2/ 76.3 mm of Hg in cases and 122.1/ 76.5 mm
of Hg in controls. It was less in cases with haemoglobin less than 6 gm/dl (118.7/ 75.2
mm of Hg), compared to cases with haemoglobin more than 9 gm/dl (122.7/ 77.3 mm of
Hg). There was no significant difference in mean blood pressure in the different types of
anaemia.
Body Mass Index

The mean body mass index was 21.5 kg/m2 in cases and 21.6 kg/m2 in controls. It
was significantly decreased (20.9 kg/m2) in cases with haemoglobin less than 6 gm/dl.
There was no significant difference of mean BMI among the various types of anaemia.
83
Table 8
Pulse rate, Blood Pressure and BMI with severity of Anaemia
Case
Haemoglobin levels(in gm/dl)
Control
(n=100)
<6
6-9
>9
Total
(n=23)
(n=40)
(n=37)
(n=100)
Mean pulse
89.3 12.8 83.6 9.8
84.9 7.5
85.4 10.0
83.7 16.9
rate
Mean systolic
118.7 9.7 121.3 8.5 122.7 10.4 121.2 9.6 122.1 15.2
blood pressure
Mean diastolic
75.2 7.9
76.1 7.7
77.3 9.0
76.3 8.2
76.5 8.4
blood pressure
Mean BMI
20.9 1.5
22.0 1.7
21.4 1.6
21.5 1.7
Increased mean pulse rate (p=0.082) as well as significantly decreased

mean BMI (p<0.01) is seen in cases with Hb < 6 gm/dl. Mean systolic
and diastolic blood pressures are not significantly different (P>0.05).
Inference
Figure 6
Pulse rate
Mean ( /minute)
21.6 1.6
90
89
88
87
86
85
84
83
82
81
80
Controls
Cases
Hb < 6
gm/dl
84
Hb 6-9
gm/dl
Hb > 9
gm/dl
Figure 7
Blood Pressure
140
120
mm of Hg
100
Systolic BP
Diastolic BP
80
60
40
20
0
Controls Cases Hb < 6
gm/dl
Hb 6-9 Hb > 9
gm/dl gm/dl
Figure 8
Body Mass Index
23
22.5
kg/ m 2
22
21.5
21
20.5
20
Controls
Cases
Hb < 6
gm/dl
85
Hb 6-9
gm/dl
Hb > 9
gm/dl
Table 9
Pulse rate, Blood Pressure and BMI with type of Anaemia
Types of Anaemia
DM
MH
NH
NN
Others
(n=40)
(n=25)
(n=18)
(n=10)
(n=7)
Mean Pulse rate 85.0 8.5
82.3 12.0
87.0 7.5
84.1 5.2
96.3 14.9
Mean systolic
120.1 9.8 122.3 8.9 118.9 8.3 126 11.7 122.9 9.5
blood pressure
Mean diastolic
75.1 6.7
75.6 10.0
77.2 8.3
79.0 8.8
80.0 8.2
blood pressure
Mean BMI
21.5 1.7
21.4 1.7
21.6 1.8
21.4 1.4
21.8 1.9
Mean pulse rate significantly higher in the others group (P<0.05).
Inference
Mean systolic and diastolic blood pressures are not significantly
different (P>0.05). Mean BMI is not significantly different (P>0.05)
Figure 9
Pulse, Blood pressure & BMI with types of Anaemia
140
120
100
Pulse (per mt)
80
SBP (mm Hg)
60
DBP (mm Hg)

BMI (kg/m2)
40
20
0
DM
MH
NH
NN
Type of Anaemia
86
Others
The most common findings on systemic examination were venous hum and flow
murmurs (9 cases each). Abdominal examination revealed 8 cases with splenomegaly and
5 cases with hepatomegaly. CNS findings were impairment of vibration sense (4 cases)
and joint position sense (2 cases), suggestive of peripheral neuropathy. Elevated JVP,
cardiomegaly, and basal crepitations were seen in 2 cases each.
Figure 10
Systemic Examination
10
9
A: JVP
B: Venous Hum
C: Cardiomegaly
D: Gallop Rhythm
E: Flow murmers
F: Basal Cepitations
G: Hepatomegaly
H: Splenomegaly
I : Confusion
J: Motor Weakness
K: Abnormal DTRs
L: Vibration Sense
M: Joint Position Sense
N: Romberg's sign
8
No of cases
7
6
5
4
3
2
1
0
A B C D
G H
M N
Systemic examination and severity of anaemia

Cardiovascular and respiratory findings such as elevated JVP, venous hum,
cardiomegaly, flow murmurs and basal crepitations were found only in cases with
haemoglobin less than 6 gm/ dl, with the exception of one case with haemoglobin
87
between 6 and 9 gm/ dl, who had a flow murmur. Impairment of vibration and joint
position sense were also found only in cases with severe anaemia. Hepatomegaly and
splenomegaly were found in all groups of cases equally.
Table 10
Systemic examination and severity of Anaemia
Systemic
Total
<6
6-9
>9
Examination
(n=100)
(n=23)
(n=40)
(n=37)
CVS
JVP
Venous hum
Cardiomegaly
Gallop rhythm
Flow murmur
RS: Basal
crepts
2
(8.7)
9
(39.1)
2
(8.7)
8
(34.8)
2
(8.7)
1
(2.5)
2
(8.7)
2
(8.7)
1
(2.5)
3
(7.5)
2
(5.4)
3
(8.1)
4
(17.4)
2
(8.7)
-
P/A
Hepatomegaly
Splenomegaly
CNS
Confusion
Power
DTRs
Vibration
Position
Romberg's
88
Systemic examination and type of anaemia

Elevated JVP, venous hum, cardiomegaly, flow murmurs and basal crepitations
were not found in cases with normocytic hypochromic anaemia and normocytic
severe anaemia. Hepatomegaly and splenomegaly was seen in all types of anaemia except
cases with normocytic normochromic blood picture. Impairment of vibration and joint
position sense was seen only in cases with dimorphic anaemia and megaloblastic
anaemia.
Table 11
Systemic examination and type of Anaemia
Types of Anaemia
Symptoms
DM
MH
NH
NN
(n=40)
(n=25)
(n=18)
(n=10)
Others
(n=7)
CVS
JVP
Venous hum
5
(12.5)
1
(4.0)
Cardiomegaly
Flow murmur
6
(15.0)
1
(4.0)
RS- Basal crepts
2
(5.0)
2
(5.0)
1
(4.0)
2
(8.0)
1
(5.6)
2
(11.1)
2
(28.6)
3
(42.6)
2
(28.6)
2
(28.6)
2
(28.6)
P/A
Hepatomegaly
Splenomegaly
1
(14.3)
2
(28.6)
CNS
Vibration
Position
3
(7.5)
1
(2.5)
89
1
(14.3)
1
(14.3)
Anaemia and Lipid profile

The mean serum total cholesterol levels were significantly lower (P<0.01) in cases
(132.2 mg/dl) as compared to controls (173.4 mg/dl). The effect of anaemia on the total
cholesterol levels was very large.
The mean serum HDL levels were significantly lower (P<0.01) in cases (31.0
mg/dl) as compared to controls (38.8 mg/dl). The effect of anaemia on the HDL levels
was large.
The mean serum LDL levels were significantly lower (P<0.01) in cases (79.7
mg/dl) as compared to controls (110.1 mg/dl). The effect of anaemia on the LDL levels
was very large.
The mean serum VLDL levels were significantly lower (P<0.01) in cases (21.6
mg/dl) as compared to controls (24.5 mg/dl). The effect of anaemia on the VLDL levels
was mild.
The mean serum triglyceride levels were significantly lower (P<0.01) in cases
(108.1 mg/dl) as compared to controls (122.5 mg/dl). The effect of anaemia on the
triglyceride levels was mild.
The mean total cholesterol / HDL ratio was significantly lower (P<0.05) in cases
(4.4) as compared to controls (4.6). The effect of anaemia on TC/HDL ratio was mild.
90
The mean LDL / HDL ratio was significantly lower (P<0.01) in cases (2.6) as
compared to controls (2.9). The effect of anaemia on LDL/HDL ratio was mild.
Table 12
Anaemia and Lipid Profile
Lipid Profile
(mean SD)
Cases (n=100)
Controls (n=100)
Significance by
Student t
Total Cholesterol
132.2 29.0
173.4 20.3
P<0.01**
HDL
31.0 6.7
38.8 7.1
P<0.01**
LDL
79.7 25.0
110.1 16.6
P<0.01**
VLDL
21.6 6.3
24.5 6.2
P<0.01**
Triglycerides
108.1 31.3
122.5 30.6
P<0.01**
TC/HDL ratio
4.4 0.8
4.6 0.7
P<0.05*M
LDL/HDL ratio
2.6 0.7
2.9 0.6
P<0.01**M
* Significant at 5%. ** Significant at 1%. M - Mann Whitney U test
Figure 11
Case
250
Control
mg/dl
200
150
100
50
0
TC
HDL
LDL
91
VLDL
TG
Effect size
(d)
1.64
(V.Large)
1.12
(Large)
1.43
(V.Large)
0.46
(Mild)
0.46
(Mild)
0.27
(Mild)
0.45
(Mild)
Severity of Anaemia and Lipid profile

The mean serum total cholesterol levels were significantly lower (P<0.01) in cases
with haemoglobin less than 6 gm/dl (106.0 mg/dl), as compared to cases with
haemoglobin more than 9 gm/dl (153.7 mg/dl).
The mean serum HDL levels were significantly lower (P<0.01) in cases with
haemoglobin less than 6 gm/dl (26.3 mg/dl), as compared to cases with haemoglobin
more than 9 gm/dl (34.5 mg/dl).
The mean serum LDL levels were significantly lower (P<0.01) in cases with
The mean serum VLDL levels were significantly lower (P<0.01) in cases with
The mean serum triglyceride levels were significantly lower (P<0.01) in cases with
The mean serum total cholesterol/HDL ratio was significantly lower (P<0.05) in
cases with Hb less than 6 gm/dl (4.1), as compared to cases with Hb more than 9 gm/dl
(4.5).
92
The mean serum LDL/HDL ratio was significantly lower (P<0.01) in cases with Hb
less than 6 gm/dl (2.4), as compared to cases with Hb more than 9 gm/dl (2.8).
Lipid Profile
(mean SD)
Table 13
Severity of Anaemia and Lipid Profile
Hb < 6 gm/dl
Hb 6-9 gm/dl
Hb > 9 gm/dl
(n=23)
(n=40)
(n=37)
P value
(ANOVA)
TC
106.0 21.3
127.5 22.5
153.7 23.6
P<0.01**
HDL
26.3 6.2
30.4 6.4
34.5 5.2
P<0.01**
LDL
61.0 19.3
75.6 21.5
95.8 22.0
P<0.01**
VLDL
18.9 7.4
21.6 5.5
23.3 5.9
P<0.01**
TG
94.4 36.7
108.1 27.9
116.5 28.8
P<0.01**
TC/HDL
4.1 0.7
4.4 0.9
4.5 0.7
P<0.05*K
LDL/HDL
2.4 0.7
2.6 0.7
2.8 0.7
P<0.01**K
* Significant at 5%. ** Significant at 1%. K - Kruskal Wallies Test
Figure 12
Severity of Anaemia and Lipid Profile
Hb < 6 gm/dl
Hb 6-9 gm/dl
Hb > 9 gm/dl
200
180
Units in
160
140
120
100
80
60
40
20
0
TC
HDL
LDL
93
VLDL
TG
Type of Anaemia and Lipid Profile

Since the severity of anaemia was found to have a significant effect on the lipid
profile, analysis of the effect of type of anaemia on lipid profile was done by further
subdividing the types of anaemia on the basis of severity and comparing the lipid profile
in groups having varying types of anaemia with similar severity.
There was no significant difference (P>0.05) in the mean total cholesterol levels in
different types of anaemia with similar levels of haemoglobin.
There was no significant difference (P>0.05) in the mean HDL levels in different
types of anaemia with similar levels of haemoglobin.
There was no significant difference (P>0.05) in the mean LDL levels in different
There was no significant difference (P>0.05) in the mean VLDL levels in different
There was no significant difference (P>0.05) in the mean triglyceride levels in
different types of anaemia with similar levels of haemoglobin.
There was no significant difference in the mean total cholesterol / HDL ratio
(P>0.05) and mean LDL / HDL ratio (P>0.05) in different types of anaemia with similar
levels of haemoglobin.
94
Table No 14
Lipid
Profile
(mean
SD)
TC
(in
mg/dl)
HDL (in
mg/dl)
LDL (in
mg/dl)
VLDL
(in
mg/dl)
TG
(in
mg/dl)
TC/
HDL
LDL/
HDL
Inference
Hb (in
gm/dl)
Type Of Anemia
P value
(ANOVA)
DM
MH
NH
NN
Others
<6
109.419.3
107.623.6
92.325.9
p>0.05
6-9
126.820.9
131.626.2
112.018.3
119.52.1
p>0.05
>9
159.622.5
144.631.2
150.823.6
164.613.0
106.00#
p>0.05
<6
22.66.6
24.63.6
23.87.4
p>0.05
6-9
31.36.1
29.27.2
30.00
30.09.9
p>0.05
>9
37.44.2
31.84.0
33.44.9
37.44.1
23.00#
p>0.05
<6
64.716.0
65.422.5
44.522.4
p>0.05
6-9
75.317.7
79.427.2
57.014.1
18.512.0
p>0.05
>9
19.218. 7
42.632.3
92.023.0
105.412.4
60.00#
p>0.05
<6
17.67.3
17.65.3
25.08.4
p>0.05
6-9
20.25.5
23.15.8
25.04.2
21.00
p>0.05
>9
23.05.0
20.24.4
25.46.7
21.85.2
23.00#
p>0.05
<6
87.636.3
89.027.3
124.841.1
p>0.05
6-9
101.527.8
115.729.3
125.021.2
103.50.7
p>0.05
>9
114.226.4
101.423.4
126.632.4
109.525.7
114.00#
p>0.05
<6
4.00.7
4.41.0
3.90.4
p>0.05K
6-9
4.10.8
4.90.9
3.70.6
4.21.5
p>0.05K
>9
4.30.7
4.61.1
4.60.8
4.40.5
4.60#
p>0.05K
<6
2.40.6
2.71.0
1.90.6
p>0.05K
6-9
2.50.6
2.90.7
1.90.5
2.51.2
p>0.05K
>9
2.70.6
2.91.1
2.80.7
2.90.5
2.60#
p>0.05K
There is no statistically significant difference in lipid fractions between different types of

anemia (P>0.05)
# - p value could not be computed as there was only one case. K - Kruskal Wallies Test
95
6. Discussion
The observations made in 100 cases of anaemia and 100 non anaemic controls, who
presented to Department of Medicine, Kempegowda Institute of Medical Sciences,
Bangalore, from June 2003 to June 2005 is discussed here and results have been
compared with other similar studies.
Age
All cases in this study were between 14 and 75 years. Majority of the cases were
middle aged (30-60 years). Anaemic cases younger than 50 years were more likely to
have more severe anaemia, as compared to cases older than 50 years, who were more
likely to have less severe anaemia. This is probably due to younger individuals having a
higher risk of worm infestations, and also the onset of menopause with cessation of
menstrual blood loss after the age of 50 years.
Sex
The cases consisted of 48 males and 52 females. There was no correlation between
sex and severity of anaemia.
Type and severity of Anaemia

Dimorphic anaemia was the most commonly seen type of anaemia in this study.
Microcytic hypochromic anaemia was the second most common, followed by normocytic
hypochromic anaemia, and those with normocytic normochromic blood picture. Only a
few cases of megaloblastic anaemia and pancytopenia, and one case of chronic myeloid
leukemia were seen. This is consistent with standard textbooks of medicine, which
96
describe nutritional deficiencies, especially iron deficiency, to be the most common cause
for anaemia25,26.
Most cases had mild to moderate anaemia, as defined by a haemoglobin level above
6 gm/dl. None of the cases with normocytic hypochromic anaemia or normocytic
normochromic blood picture had severe anaemia.
Symptoms
Cases commonly presented with non specific symptoms of anaemia, such as
fatigue, dyspnoea, palpitations and giddiness. Symptoms suggestive of a specific cause
for anaemia were rarely seen.
Cases with more severe anaemia were more likely to have symptoms and had more
number of symptoms. Patients with haemoglobin more than 10 gm/dl were usually
asymptomatic, and incidentally detected to have on anaemia on routine evaluation. This
is consistent with standard textbooks of medicine which state that mild anaemias of
insidious onset are usually asymptomatic26.
Non specific symptoms such as fatigue, dyspnoea, giddiness, palpitations, fever,

loss of appetite and loss of weight were equally frequent in the different types of
anaemia, except normocytic hypochromic anaemia and cases with normocytic
severe anaemia.
97
Personal history
19 cases were vegetarians. Vegetarians were more likely to have more severe
anaemia and to have dimorphic anaemia. Vegetarians are likely to have more severe
anaemia as dietary iron of plant origin has less bioavailability.

Pallor was the most common finding on general physical examination. Cases with
more severe anaemia were found to be more likely to have findings on general physical
examination. Signs were usually not seen in cases with haemoglobin less than 10 gm/dl.
Koilonychia, lymphadenopathy, glossitis and angular stomatitis were seen only in cases
with dimorphic anaemia and microcytic hypochromic anaemia. Knuckle pigmentation
and perioral pigmentation was seen only in cases with megaloblastic anaemia and
dimorphic anaemia. This is consistent with descriptions given in standard textbooks of
medicine25.
Pulse Rate
The mean pulse rate was higher in anaemic cases when compared to non anaemic
controls. The mean pulse rate was higher in cases with more severe anaemia. The pulse
rate has been described to be higher in case of anaemia, in standard textbooks of
medicine. This is part of a compensatory mechanism to raise cardiac output and maintain
tissue oxygenation34.
98
Ickx, Rigolet and Linden33, in 2000, demonstrated that anaemia causes a rise in
pulse rate and stroke volume in patients whose haemoglobin was lowered from 13 gm/dl
to 8 gm/dl.
Blood Pressure
The mean blood pressure was comparable in cases and controls. It was lower in
cases with more severe anaemia. This is due to peripheral vasodilatation, another
compensatory mechanism to raise cardiac output and maintain tissue oxygenation.
Duke and Abelmann31, in 1969, demonstrated that redistribution of blood volume

and vasodilatation played a dominant role in the hyperkinetic circulatory response to
chronic anaemia.
Body Mass Index

The mean body mass index was comparable in cases and controls. It was lower in
cases with more severe anaemia.
The most common findings on systemic examination were venous hum and flow
murmurs. Features suggestive of hyperdynamic state of circulation and congestive
cardiac failure were only seen in cases with severe anaemia. Features suggestive of
peripheral neuropathy were seen only in cases with megaloblastic anaemia and dimorphic
anaemia.
99
This was consistent with a study done by Graettinger, Parsons and Campbell35 in
1983, which demonstrated that anaemia leads to significant haemodynamic changes only
when it is severe.

The results of this study confirm the findings of previous investigators that the
mean serum total cholesterol, HDL, LDL, VLDL and triglyceride levels are decreased in
anaemia.
The mean total cholesterol was found to be lower in anaemic cases when compared
to controls. The decrease in mean serum cholesterol was not due to a specific lowering of
any of the serum lipoprotein families; hypocholesterolemia was caused by a reduction in
all the major lipoprotein families, including mean HDL, LDL, VLDL and triglycerides.
There was a very large decrease in mean total cholesterol and LDL levels, and a large
decrease in mean HDL levels, resulting in a mild fall in mean TC/HDL and LDL/HDL
ratios. There was a mild decrease in mean VLDL and triglyceride levels.
Rifkind and Gale4,5 in 1967 showed that anaemia was associated with
hypocholesterolemia and the decrease in serum cholesterol was not due to a specific
lowering of any of the serum lipoprotein families, and that hypocholesterolemia was
caused by a proportional reduction in all the major lipoprotein families.
100
Elwood and Mahler6, in 1970, conducted a study 4,070 women, and demonstrated a
significant difference in cholesterol between women with haemoglobin levels above and
below 10.5g/dL.
Severity of Anaemia and Lipid profile

Patients with more severe anaemia were found to have a larger fall in mean total
cholesterol and all the lipid sub fractions. This suggests that the severity of anaemia is
responsible for the hypocholesterolemia seen in anaemia.
A study conducted by Choi61 et al in 2001 showed that lipid levels in patients with
iron deficiency anaemia were directly related to the hemoglobin levels.

The type of anaemia did not have a significant effect on the mean lipid levels. This
suggests that it is anaemia per se, and not the type of anaemia that is responsible for the
lowering of lipid levels in anaemia.
study
by
Westerman7
in
1975
examined
the
relationship
between
hypocholesterolemia and various types of anaemia, including megaloblastic anaemia,

hereditary spherocytosis, homozygous sickle cell disease, aplastic anaemia, and liver
associated anaemia. The study showed that the plasma cholesterol level is closely related
to haematocrit levels, both initially and throughout the course of the anaemias associated
with hypocholesterolemia. This association was maintained regardless of the cause of
101
changes in haematocrit levels. The authors concluded that low haematocrit, not the type
of anaemia, is the cause of low cholesterol levels.
Seip and Skrede56, in 1967, found an association between serum cholesterol and
haemoglobin in all cases, regardless of cause of anaemia.
102
7. Conclusion
100 cases of anaemia and 100 controls who presented to the Department of
Medicine, Kempegowda Institute of Medical Sciences, Bangalore, from June 2003 to
June 2005 are presented here. They were studied regarding demographic characteristics,
clinical presentation and biochemical changes with special reference to lipid profile in
relation to severity and type of anaemia. The following conclusions were arrived at.
1) Majority of cases with anaemia were in the age group of 30-60 years. Younger
cases were more likely to have more severe anaemia.
2) There was no relation between sex and severity of anaemia
3) Dimorphic anaemia was the most commonly seen type of anaemia.
4) Most cases had mild to moderate anaemia.
5) The most common presenting symptom was fatigue. Patients with severe anaemia
were more likely to be symptomatic.
6) Vegetarians were more likely to have more severe anaemia.
7) Pallor was the most common finding on general physical examination. Cases with
more severe anaemia were more likely to have findings on general physical
examination.
103
8) The mean pulse rate was higher in cases. The mean pulse rate was higher in cases
with severe anaemia. The mean blood pressure and BMI were lower in cases with
severe anaemia.
9) The most common findings on systemic examination were venous hum and flow
murmurs. Features suggestive of hyperdynamic state of circulation and congestive
cardiac failure were only seen in cases with severe anaemia.
10) The mean total cholesterol, HDL, LDL, VLDL and triglyceride levels, along with
TC/HDL and LDL/HDL ratios were significantly decreased in cases compared to
controls.
11) There was a larger reduction in mean total cholesterol, HDL, LDL, VLDL and
triglyceride levels, along with TC/HDL and LDL/HDL ratios with increased
severity of anaemia.
12) The type of anaemia did not have a significant effect on the mean lipid levels.
104
8. Summary
This study was done on 100 anaemic cases and 100 non anaemic controls to study
the clinical presentation and effect on lipid profile of anaemia.
Younger individuals are more likely to have severe anaemia. Cases with severe
anaemia have more symptoms. They have higher mean pulse rate, lower mean blood
pressure and mean BMI. Vegetarians are more likely to have severe anaemia. Cases with
severe anaemia also have more signs on examination.
Anaemia is associated with significant hypocholesterolemia, with lowering in all

lipid subfractions. The extent of hypocholesterolemia is proportional to the severity of
anaemia. The type of anaemia has no effect on the hypocholesterolemia seen in anaemia.
Further studies are required to study the long term effect of anaemia on the risk of
developing atherosclerosis, and to study the long term effect of treatment of anaemia on
lipid levels and cardiovascular morbidity and mortality1.
105
9. Bibliography
1. Atac B, Brahaj D, Frishman WH, Lerner R. Anemia and hypocholesterolemia.
Heart Disease. 2003;5:65-71.
2. Braunwald E, Zipes DP, Libby P. Heart Disease. 6th ed. Philadelphia: W B
Saunders Company; 2001. p. 1010-5.
3. Albert S, Lyons MD, Joseph R, Petaricelli. Medicine illustrated history. Abranale:
Harry N Abrams Inc; 1987.
4. Rifkind BM, Gale M. Hypolipidemia in anaemia: Implications for the
epidemiology of ischemic heart disease. Lancet. 1970 Sep 23;1:640-642.
5. Rifkind BM, Gale M. Hypolipidemia in anemia. Am Heart J. 1968 Dec;76:849850.
6. Elwood PC, Mahler R, Sweetnam P, Moore F. Association between circulating
haemoglobin level, serum cholesterol and blood pressure. Lancet. 1970 Mar
21;1:589-590.
7. Westerman MP. Hypocholesterolemia and anemia. Br J Hematol. 1975;31:87-94.
8. Burtis CA, Ashwood ER. Tietz. Textbook of Clinical Chemistry. 3rd ed.
Philadelphia: W B Saunders Company; 1999. p. 809-35.
9. Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 3rd ed. New York:
Worth Publishers; 2000. p. 598-618, 770-813.
10. Guyton AC, Hall GE. Textbook of Medical Physiology. 10th ed. Philadelphia:
Saunders; 2000. p. 728-63.
11. Ganong WF. Review of Medical Physiology. 21st ed. Boston: McGraw-Hill;
2003. p. 477-9.
106
12. Murray RK, Granner DK, Mayes PA, Rodwell VW. Harpers Biochemistry. 24th
ed. London: Prentice-Hall International; 1996. p. 254-70.
13. Young SG. Recent progress in understanding apolipoprotein B. Circulation. 1990
Nov;82(5):1574-1594.
14. Castelli WP, Garrison RJ, Wilson PWF, Abbot RD, Kalousdian S, Kannel WB.
Incidence of coronary heart disease and lipoprotein cholesterol levels. JAMA.
1986 Nov 28;256(20):2835-2838.
15. The Multiple Risk Factor Intervention Trial Research Group. Mortality rates after
10.5 years for participants in the Multiple Risk Factor Intervention Trial: findings
related to a priori hypothesis of the trial. JAMA 1990; 263:1795-1801.
16. Keys A. Seven Countries. A Multivariate Analysis of Death and Coronary Heart
Disease. Cambridge: Harward University Press:1980.
17. Gotto AM. Cholesterol intake and serum cholesterol level. N Engl J Med. 1991
Mar 28;324(13):912-913.
18. National Cholesterol Education Program Expert Panel. Executive summary of the
third report of the National Cholesterol Education program (NCEP) Expert Panel
on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults
(Adult Treatment Panel III). JAMA. 2001 May16;285:2486-2497.
19. Consensus Conference. Lowering blood cholesterol to prevent heart disease.
JAMA. 1985 Apr 12;253(14):2080-2086.
20. Fuster V, Alexander RW, ORourke RA. Hursts The Heart. 11th ed. New York:
McGraw-Hill; 2004. p. 1123-39.
107
21. Ross R. Atherosclerosis, an inflammatory disease. N Engl J Med. 1999 Jan

14;340(2):115-126.
22. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet.1994 Sep
17;344:793-795.
23. Larsen PR, Kronenberg HM, Melmed S, Polonsky KS. Williams Textbook of
Endocrinology. 10th ed. Philadelphia: Saunders; 2003. p. 1667-82.
24. Allen JM, Thompson GR, Myant NB, Steiner R, Oakley CM. Cardiovascular
complications of homozygous familial hypercholesterolemia. Br Heart J.
1980;44:361-368.
25. Greer JP, Foerster J, Lukens JN, Rodgers GM, Paraskevas F, Glader B.
Wintrobes Clinical Hematology. 11th ed. Philadelphia: Lippincott Williams &
Wilkins;2004. p. 947-1486. vol 1.
26. Warrel Da, Cox TM, Firth JD, Benz Jr EJ. Oxford Textbook of Medicine. 4th ed.
Oxford: Oxford University Press; 2003. p. 639-48.
27. Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease.
7th ed. Philadelphia: Saunders; 2004. p. 622-4.
28. DeMaeyer E, Adiels-Tegman M. The prevalence of anaemia in the world. World
Health Statistics Quarterly. 1985;38:302-316.
29. Shah SN. API Textbook of Medicine. 7th ed. Mumbai: The Association of
Physicians of India; 2003. p. 930.
30. Allen JB, Allen FB. The minimum acceptable level of hemoglobin. Int
Anesthesiol Clin 1982;20:1-22.
108
31. Duke M, Abelmann WH. The hemodynamic response to chronic anemia.

Circulation. 1969 Apr;39:503-515.
32. Weiskopf RB, Feiner J, Hopf H, Viele MK, Watson JJ, Lieberman J, et al. Heart
rate increases linearly in response to acute isovolemic anemia. Transfusion. 2003
Feb;43(2):235-240.
33. Ickx BE, Rigolet M, Van der Linden PJ. Cardiovascular and metabolic response
to acute normovolemic anemia. Anesthesiology. 2000 Oct;93(4):1011-1016.
34. Varat MA, Adolph RJ, Fowler NO. Cardiovascular effects of anemia. Am Heart J.
1972 Mar;83(3):415-426.
35. Graettinger JS, Parsons RL, Campbell JA. A correlation of clinical and
hemodynamic studies in patients with mild and severe anemia with and without
congestive failure. Ann Intern Med. 1963 Apr;58(4):617-626.
36. Ioannou GN, Rockey DC, Bryson CL, Weiss NS. Iron deficiency and
gastrointestinal malignancy: A population based cohort study. Am J Med. 2002
Sep;113:276-280.
37. Zinner MJ, Schwartz SI, Ellis H. Maingots Abdominal Operations. 10th ed.
London: Prentice Hall International; 1997. p. 289-313.
38. Bhatla N. Jeffcoates Principles of Gynaecology. 6th ed. London: Arnold; 2001. p.
560-80.
39. Handin RI, Lux SE, Stossel TP. Blood: Principles & Practice of Hematology.
Pliladelphia: JB Lippincott Company; 1995. p. 1733-923.
40. Tse WT, Lux SE. Red blood cell membrane disorders. Br J Haematol.
1999;104:2-13.
109
41. Beutler E. Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med. 1991

Jan 17;324(3):169-174.
42. Firkin F, Chesterman C, Pennigton D, Rush B. de Gruchys Clinical Haematology
in Medical Practice. 5th ed. Oxford: Oxford University Press; 1989. p. 137-71.
43. Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997
Sep 11;337(11):762-769.
44. Oliveri NF. The -Thalassemias. N Engl J Med. 1999 Jul 8;341(2):99-109.
45. Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N
Engl J Med. 1997 May 8;336(19):1365-1372.
46. Brown KE, Tisdale J, Barrett J, Dunbar CE, Young NS. Hepatitis associated
aplastic anemia. N Engl J Med. 1997 Apr 10;336(15):1059-1064.
47. Fisch P, Handgretinger R, Schaefer HE. Pure red cell aplasia. Br J Haematol.
2000;111:1010-1022.
48. Brenner BM. Brenner & Rectors The Kidney. 7th ed. Philadelphia: Saunders;
2004. p. 2165-73. vol 2.
49. Hoffman R, Benz Jr EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE et al.
Hematology: Basic Principles and Practice. 4th ed. Philadelphia: Elsevier
Churchill Livingstone; 2005. p. 514-56.
50. Toh B, Van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med. 1997 Nov
13;337(20):1441-1448.
51. Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999 Dec
23;341(26):1986-1995.
110
52. Cazzola M, Barosi G, Gobbi PG, Inverizzi R, Riccardi A, Ascari E. Natural

history of idiopathic refractory sideroblastic anemia. Blood. 1988 Feb;71(2):305312.
53. Beutler E, Lichtman M, Coller BS, Kipps TJ, Seligsohn U. Williams Hematology.
6th ed. New York: McGraw-Hill; 2001. p. 481-7.
54. Savage D, Lindenbaum J. Anemia in alcoholics. Medicine. 1986;65(5):322-338.
55. El-Hazmi MAF, Jabbar FA, Warsu AS. Cholesterol and triglyceride levels in
patients with sickle cell anemia. Scan J Clin Lab Invest. 1987;47:351-354.
56. Seip M, Srede S. Serum Cholesterol and triglycerides in children with anemia.
Scan J Hematol. 1967;19:503-508.
57. Dessu S, Batetta B, Spano O. Serum lipoprotein pattern as modified in G6PD
deficient children during hemolytic anemia induced by fava bean ingestion. Int J
Exp Pathol. 1992;73:157-160.
58. El-Hazmi MAF, Warsy AS, Al-Swailem A, Al-Swailem A, Bahakim H. Red cell
genetic disorders and plasma lipids. J Trop Pediatr. 1995 Aug;41:203-205.
59. Akinyanju PA, Akinyanju CP. Plasma and red cell lipids in sickle cell disease.
Ann Clin Lab Sci. 1976;6:521-524.
60. Au YPT, Schilling RF. Relationship between anemia and cholesterol metabolism
in sex linked anemic mouse. Biochim Biophys Acta. 1986;883:242-246.
61. Choi JW, Kim SK, Pai SH. Changes in serum lipid concentration during iron
depletion and after iron supplementation. Ann Clin Lab Sci. 2001;31(2):151-156.
111
62. Tanzer F, Hizel S, Cetinkaya O, et al. Serum free carnitine and total triglyceride
levels in children with iron deficiency anemia. Int J Vitam Nutr Res. 2001;71:6669.
63. Nimer SD, Champlin RE, Golde DW. Serum cholesterol lowering activity of
granulocyte-macrophage colony stimulating factor. JAMA. 1988 Dec 9;260:32973300.
64. Vitols S, Gahrton G, Bjorkholm M, Peterson C. Hypocholesterolemia in
malignancy due to elevated low density lipoprotein receptor activity in tumour
cells: Evidence from studies in patients with leukemia. Lancet. 1985 Nov
23;2:1150-1153.
65. Juliusson G, Vitols S, Liliemark J. Disease-related hypocholesterolemia in
patients with hairy cell leukemia. Positive correlation with spleen size but not
with tumor cell burden or low density lipoprotein receptor activity. Cancer.
1995;76:423-428.
66. Gilbert
HS,
Ginsberg
H,
Fagerstrom
R,
et
al.
Characterization
of
hypocholesterolemia in myeloproliferative disease. Am J Med. 1981;71:595-602.

67. Deiana L, Garuti R, Pes GM, et al. Influence of beta(0)-thalassemia on the
phenotypic expression of heterozygous familial hypercholesterolemia: a study of
patients with familial hypercholesterolemia from Sardinia. Arterioscler Thromb
Vasc Biol. 2000;20:236-243.
68. Gilbert HS, Ginsberg H, Fagerstrom R, Brown WV. Characterization of
hypocholesterolemia in myeloproliferative disease. Am J Med. 1981 Oct;71:595602.
112
69. Gilbert HS, Ginsberg H. Hypocholesterolemia as a manifestation of disease

activity in chronic myeloid leukemia. Cancer. 1983;51:1428-1433.
70. Hashmi JA, Afroz N. Hypolipidemia in anemia. Am Heart J. 1968;78:840.
71. Mat O, Stolear JC, Georges B. Blood lipid profiles in hemodialysis patients
treated with human erythropoietin. Nephron. 1992;60:236-237.
72. Hartman C, Tamary H, Tamir A, Shabad E, Levine C, Koren A, et al.
Hypocholesterolemia in children and adolescents with beta-thalassemia
intermedia. J Pediatr 2002 Oct;141(4):543-547.
73. VanderJagt
DJ,
Shores
J,
Okorodudu
A,
Okolo
SN,
Glew
RH.
Hypocholesterolemia in Nigerian children with sickle cell disease. J Trop Pediatr.

2002 Jun;48(3):156-161.
74. Evans JG, Prior IAM. Hypolipidemia in anaemia. Lancet. 1967 Dec 23;2:13621363.
75. Boga M, Szemere PA. Relation between serum cholesterol and haemoglobin
values. Br Med J. 1973 Apr 14;119.
76. Bottiger LE, Carlson LA. Relation between serum cholesterol and triglyceride
concentration and haemoglobin values in non anaemic healthy persons. Br Med J.
1972 Sep 23;3:731-733.
77. Sullivan JL. Iron and the sex difference in heart disease risk. Lancet. 1981 Jun
13;1:1293-1294.
78. McCord JM. Is iron sufficiency a risk factor in ischemic heart disease?
Circulation. 1991 Mar;83(3):1112-1114.
113
79. Williams RE, Zweier JL, Flaherty JT. Treatment with deferoxamine during
ischemia improves functional and metabolic recovery and reduces reperfusion
induced oxygen radical generation in rabbit hearts. Circulation. 1991
Mar;83(3):1006-1014.
80. Rosner B. Fundamentals of Biostatistics. 5th ed, Duxbury; 2000.
81. Reddy MV. Statistics for Mental Health Care Research. NIMHANS publication;
2002.
114
10. Annexures
I. Proforma
A Study of Lipid Profile in Anaemia
Case/Control No:
Matched with Case/Control

No:
Preliminary data of the Patient

Name:
Age:
years
Sex:
Occupation:
OP/IP No:
Unit: Med
History of Presenting Illness:

Fatigue
Yes/ No
Dyspnoea
Yes/ No
Giddiness
Yes/ No
Palpitations
Yes/ No
Angina
Yes/ No
Pica
Yes/ No
Dysphagia
Yes/ No
Abd pain
Yes/ No
Bony pain
Yes/ No
Fever
Yes/ No
Loss of appetite
Yes/ No
Weight loss
Yes/ No
115
Date:
M/F
Jaundice
Yes/ No
Bleeding
Yes/ No
Malaena
Yes/ No
Haemoglobinuria
Yes/ No
Menorrhagia
Yes/ No
Pregnancy
Yes/ No
Post menopausal bleeding
Yes/ No
Past History:
Diabetes Mellitus
Yes/ No
Hypertension
Yes/ No
IHD
Yes/ No
CVA
Yes/ No
AIDS
Yes/ No
Recent blood loss
Yes/ No
Gall stones
Yes/ No
Personal History:
Diet:
Veg/ Non veg
Smoking
Yes/ No
Alcohol
Yes/ No
Drug History:
Oral Contraceptives
Yes/ No
116
Beta blockers
Yes/ No
Diuretics
Yes/ No
Steroids
Yes/ No
NSAIDs
Yes/ No
Family History
Anaemia
Yes/ No
Jaundice
Yes/ No
Gallstones
Yes/ No
On Examination:
Pallor
Yes/ No
Koilonychia
Yes/ No
Icterus
Yes/ No
Pedal edema
Yes/ No
Lymphadenopathy
Yes/ No
Glossitis
Yes/ No
Angular stomatitis
Yes/ No
Petechiae
Yes/ No
Haemolytic facies
Yes/ No
Ankle ulcers
Yes/ No
Perioral pigmentation
Yes/ No
Knuckle pigmentation
Yes/ No
Pulse:
/min
Rhythm
BP:
mm of Hg
Volume
117
Weight:
kgs
Height:
cms
Body Mass Index:
kg/m2
Cardiovascular system
JVP
Yes/ No
Venous hum
Yes/ No
Cardiomegaly
Yes/ No
S3
Yes/ No
Flow murmer
Yes/ No
cms
Respiratory system
Basal crepitations
Yes/ No
Abdomen
Hepatomegaly
Yes/ No
Splenomegaly
Yes/ No
Central nervous system

Confusion
Yes/ No
Power
DTRs
Vibration
Normal/ Impaired
Position
Normal/ Impaired
Rombergs
Present/ Absent
118
Investigations:
1. Complete Haemogram
Hb
g/dl
PCV
%,
TC
* 103 /mm3
DC
%P
%L
%E
ESR
mm/hr
RBC
*106 /mm3
MCV
fL
MCH
pg
MCHC
g/dl
Peripheral Smear:
2. Lipid Profile
Total Cholesterol
mg/dl
HDL
mg/dl
LDL
mg/dl
VLDL
mg/dl,
Triglycerides
mg/dl
TC/ HDL Ratio

LDL/ HDL Ratio
119
%M
%B,
3. Urine Routine
Albumin
Sugar
Microscopy
PC / HPF
EPC / HPF
RBC / HPF
4. Random Blood Sugar
mg/dl
5. Blood Urea
mg/dl
6. Serum Creatinine
mg/dl
7. Liver Function Tests

Serum total bilirubin
mg/dl
Serum direct bilirubin
mg/dl
SGOT
U/L
SGPT
U/L
SAP
U/L
Serum total protein
gm/dl,
Serum albumin
gm/dl
Albumin/ Globulin Ratio
120
8. Thyroid Profile
9.
TSH
U/ml
T3
ng/dl
T4
g/dl
FBS
mg/dl
PPBS
mg/dl
10. Bone Marrow Aspiration Cytology
121
II. Master Chart

Key to Master Chart
DM
Diabetes mellitus
HTN
Hypertension
IHD
Ischemic heart disease
CVA
Cerebrovascular accident
AIDS
Acquired immunodeficiency syndrome
OCs
Oral contraceptives
BP
Blood pressure
Wt
Weight
Ht
Height
BMI
Body mass index
CVS
Cardiovascular system
JVP
Jugular venous pressure
RS
Respiratory system
P/A
Per Abdomen
CNS
Central nervous system
DTRs
Deep tendon reflexes
Hb
Haemoglobin
PCV
Haematocrit
TC
Total count
Polymorphs
Lymphocytes
122
Eosinophils
Monocytes
Basophils
ESR
Erythrocyte sedimentation rate
MCV
Mean corpuscular volume
MCH
Mean corpuscular haemoglobin
MCHC
Mean corpuscular haemoglobin concentration
STC
Serum total cholesterol
HDL
High density lipoprotein
LDL
Low density lipoprotein
VLDL
Very low density lipoprotein
TG
Triglycerides
PCs
Pus cells
EPCs
Epithelial cells
RBCs
Red blood cells
RBS
Random blood sugar
FBS
Fasting blood sugar
PPBS
Post prandial blood sugar
STB
Serum total bilirubin
SDB
Serum direct bilirubin
SGOT
Serum glutamate oxaloacetate aminotranferase
SGPT
Serum glutamate pyruvate aminotransferase
SAP
Serum alkaline phosphatase
123
A/G
Albumin/ globulin ratio
TSH
Thyroid stimulating hormone
T3
3,5,3-Triiodothyronine
T4
Thyroxine
124

Study of Lipid Profile in Anemia

Diunggah oleh

Informasi Dokumen

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Study of Lipid Profile in Anemia

Diunggah oleh

Hak Cipta:

Format Tersedia

A STUDY OF LIPID PROFILE

Dr. Zayed Abdulla

Dissertation Submitted to the

Under the guidance of

Professor Chikkalingaiah. M.D.

Department of General Medicine

Rajiv Gandhi University Of Health Sciences, Karnataka, Bangalore

DECLARATION BY THE CANDIDATE

Signature of the Candidate

Name: Dr. Zayed Abdulla

CERTIFICATE BY THE GUIDE

This is to certify that the dissertation entitled A Study of Lipid Profile in

Anaemia is a bonafide research work done by Dr. Zayed Abdulla in partial

Signature of the Guide

Name: Dr. Chikkalingaiah. M.D.

CERTIFICATE BY THE CO-GUIDE

This is to certify that the dissertation entitled A Study of Lipid Profile in

Anaemia is a bonafide research work done by Dr. Zayed Abdulla in partial

Signature of the Co-Guide

Name: Dr K.L. Mahadevappa, Ph.D.

ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF THE

Seal & Signature of the HoD

Seal & Signature of the Principal

Name: Dr. V. Channaraya. M.D., DNB, F.I.C.C.,

Name: Dr. M. K. Sudarshan. M.D.,

Professor & HoD,

Medical Sciences, Bangalore.

Medical Sciences, Bangalore.

Signature of the Candidate

Name: Dr. Zayed Abdulla

Rajiv Gandhi University of Health Sciences, Karnataka

I am indebted to Dr. K.M. Govindaraju M.S., Medical Superintendent, KIMS

Signature of the Candidate

Name: Dr. Zayed Abdulla

LIST OF ABBREVIATIONS USED

Acquired immune deficiency syndrome

Body mass index

Cholesteryl ester transfer protein

Coronary heart disease

Deoxyribo nucleic acid

Reduced flavin adenine dinucleotide

Fasting blood sugar

Glucose 6 phosphate dehydrogenase

Granulocyte-macrophage colony stimulating factor

General physical examination

Hairy cell leukemia

High density lipoprotein

Heparan sulphate proteoglycans

Intermediate density lipoproteins

Jugular venous pulse

Kempegowda Institute of Medical Sciences

Lecithin:Cholesterol acyl transferase

Low density lipoprotein

Low density lipoprotein receptor related protein

Mean corpuscular haemoglobin

Mean corpuscular haemoglobin concentration

Monocyte chemoattractant protein 1

Mean corpuscular volume

Microcytic hypochromic anaemia

Microsomal transfer protein

Reduced nicotinamide adenine dinucleotide

National cholesterol education program

Normocytic hypochromic anaemia

Normocytic normochromic blood picture