Blood and Current Concepts in Coagulation with Applied Aspect

BLOOD &
CURRENT
CONCEPTS IN
COAGULATION
WITH APPLIED
ASPECTS
PRESENTED BY:
DR. SUSMITA SHAH
MDS PART- I
DEPARTMENT OF PAEDIATRICS & PREVENTIVE DENTISTRY
K.M.S.D.C.H

 CONTENTS
1. INTRODUCTION
2. BLOOD: PROPERTIES, COMPOSITION,
FUNCTION
3. BLOOD PLASMA
4. HEMOPOIESIS
5. RBC
6. BLOOD INDEX
7. HEMOLYSIS 1/13/2019 3

1. INTRODUCTIO
N
What is Blood?
Blood is circulating tissue composed of fluid plasma & cells
(RBC, WBC, Platelets).
Terms related to blood starts with-haemo/haemato; derived from
Greek word ‘haima’
It is connective tissue in fluid form.
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Guyton and Hall Text book of medical physiology 12thedition 2011.
Ganong Review of Medical Physiology-23rd Edition.
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2. PROPERTIES
• Colour-Red
• Forms 6-8% of total body weight.
• pH- 7.4
• Viscosity- 3 to 5 times viscous than water
• Specific gravity- 1.052 to 1.061
• Circulating blood volume will be lesser than total blood volume
• Average volume: Males- 5 Litres
Females- 4.5 Litres
New Borns- 450 ml
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• TONICITY
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• COMPOSITION
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• FUNCTIONS OF
BLOOD
1. Supply of Oxygen & Nutrients(glucose, Amino acids, Fatty acids)
2. Removal of wastes(CO2, Urea, lactic acid)
3. Immunological functions(circulation WBC’s, detection of foreign
materials-by ANTIBODIES)
4. Coagulation- Response to blood vessels
5. Messenger function- Transport of Hormones & Signaling of tissue
damage
6. Regulation of pH & Body Temperature
7. Hydraulic functions
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COMPONENTS OF PLASMA
• Organic components
1. Plasma protein
2. Amino acids
3. Carbohydrates
4. Fat
5. Hormones
6. Enzymes
7. Antibodies
• Inorganic components
1. Na
2. Ca
3. K
4. Mg
5. Cl
6. Fe
7. Cu
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4. HEMOPOIESIS
• Hemopoiesis is process of formation of blood cellular
components.
• All cellular components are derived from pluripotent
haemopoietic stem cells.
• In a healthy adult, approximately 1011-1012 new blood cells are
produced daily in order to maintain steady state levels in
peripheral circulation.
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• FACTORS FOR
HEMOPOIESIS
• Humoral regulation by hormones
• Erythropoietin
• Leucopoietin
• Thrombopoietin
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5. RED BLOOD CELLS
• Also known as Erythrocytes.
• Most abundant cells of blood.
• Transports hemoglobin, which in turn carries oxygen from lungs to
the tissues.
Normal value
• Male: 5-6 million/mm3
• Female: 4.5-5.5 million/mm3
• Infant: 6-7 million/mm3
Guyton and Hall Text book of medical physiolog 12th edition 2011.
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• MORPHOLOGY OF
RBC’S
• Oval biconcave discs & they are flexible.
• Approximately disk diameter- 6.2 to 8.2 micromillimeter
• Lack in cell nucleus-accommodate maximum space for haemoglobin.
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• Thickness: 2.5 micrometers at the thickest point and 1micrometer or
less in the center.
The average volume: 85 to 90 cubic micrometers.

• FORMATION OF
RBC’S
-The process is called as Erythropoiesis
Prenatal: 3RD Week-3rd month- yolk sac
3rd month-5th month- liver
5th month onwards- RBM
Post- natal: red bone marrow
• Approximately 2.4 million new RBC’s are produced per second.
• RBC circulates in body for around 100-120 days.
• Human blood cells take average 20 sec to complete one cycle of
circulation.
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• FUNCTIONS OF
RBC’S
• The major function of RBC’s is to transport hemoglobin &in turn
carries oxygen from lungs to tissues.
• Red blood cells contains carbonic anhydrase which catalyzes the
reaction between carbon dioxide & water, that has significance in
transporting carbon dioxide from tissues to lungs.
• Blood group determination.
• Excellent acid base buffer.
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• VARIATIONS OF
RBC’S
A. Variations in count
B. Variations in shape
C. Variations in size
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A. VARIATION IN COUNT
1.ERYTHROCYTOSIS
Is an increase in circulating rbc’s above normal level.
It can be primary & secondary.
• Pathological
1.Primary- Bone marrow
disorder
2. Secondary- Cardiovascular
disorder, respiratory disorder
• Physiological
1. Absolute- high altitude
2. Relative- exercise
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2. ERYTHROPENIA
• It is decrease in RBC’s count below normal level
• Deficiency in number of RBC’s or decreased level of hemoglobin in
RBC’s is called as anemia.
• It may be because of reduced production, lysis of RBC’s or blood loss.
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• Pathological
1. Primary-bone marrow disorder
2. Secondary- due to any kidney
disease
• Physiological
1. Absolute- reduced production
2. Relative- pregnancy

B. VARIATIONS IN SHAPE
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1. Crenation- hypertonic condition(shrinkage)
2. Spherocytosis- hypotonic condition(globular)
3. Sickle cell- cresentic(sickle cell anemia)
4. Poikilocytosis- unusual shape because of
deformed cell membrane

PATHOLOGIC
AL SHAPES
OF RBC
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C. VARIATION IN SIZE
1. Microcytes- (less than 6 𝜇) iron deficiency anemia, prolonged
forced breathing, increased osmotic pressure.
2. Macrocytes- (8 to 9 𝜇 )megaloblastic anemia, muscular
exercise, decreased osmotic pressure.
3. Megalocytes- (9 to 12 𝜇)
4. Normocytes- (6.2 to 8.2𝜇)
5. Anisocytes- pernicious anemia
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6. BLOOD INDICES
HELPS IN DIAGNOSIS
a. PACKED CELL VOLUME (PCV)
b. MEAN CORPUSCULAR VOLUME (MCV)
c. MEAN CORPUSCULAR HEMOGLOBIN (MCH)
d. MEAN CORPUSCULAR HEMOGLOBIN CONCENTRATION (MCHC)
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a. HEMATOCR
IT
• It is also known as packed cell volume (PCV)
or erythrocyte volume fraction(EVF) it is
volume % of RBC in blood.
• It is normally around 40-48% for men & 36-
42% for female
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SIGNIFICANCE OF DETERMINING
PCV :-
• Diagnosis and tx of anemia
• Diagnosis and tx of polycythemia
• Determination and extent of dehydration and recovery from that
• Decision of blood transfusion
• Variation in PCV
• Increases in polycythemia and dehydration
• Decreases in anemia, and pregnancy
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b. MEAN CORPUSCULAR VOLUME(MCV)
• It is average value of a single red blood cell and it is expressed in cubic
micron.
• Normal mcv is 90 cu micron.
• Mcv= volume of packed cell in ml per liter of blood
• Red cells in million per cu. Mm
• More in pernicious anemia and megaloblastic anemia
• Less in iron deficiency anemia
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c. MEAN CORPUSCULAR HEMOGLOBIN(MCH)
• It is the quantity of hemoglobin present in one red blood cell.
• It is expressed in pico gram (pg)
Hb gm/liter of blood
Red cell in million /cu mm
• It decreases in pernicious anemia and megaloblastic
anemia.
•
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d. MEAN CORPUSCULAR HEMOGLOBIN
CONCENTRATION(MCHC)
• This is concentration of one red blood cell.
• Expressed in percentage.
• Normal value is 30%
Hb in grams/100ml X 100
Volume of packed cell in 100ml
• Increased in iron deficiency anemia
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7. HEMOLYSIS OF
RBC
• Heme- blood ; lysis- destruction
• Also known by the rupturing of red blood cells and the release of their
contents (cytoplasm) into surrounding fluid (e.g. Blood plasma).
• Hemolysins damage the host cytoplasmic membrane, causing cell lysis
and death.
• Hemolysis can lead to hemoglobinemia due to hemoglobin released
into the blood plasma.
• Hemolysis can be invitro or invivo.
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CAUSES
Hemolysis inside the body can be caused by a large
number of medical conditions, including many gram-positive
bacteria (e.g., Streptococcus, enterococcus,
and staphylococcus), some parasites (e.g., Plasmodium),
some autoimmune disorders (e.g., Drug-induced hemolytic
anemia), some genetic disorders (e.g., Sickle-cell
disease or G6PD deficiency), or blood with too low a solute
concentration (hypotonic to cells).
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• Inherited defects in the blood cells
• (E.G., Hereditary spherocytosis , thalassemia) chemicals,
venoms
• The toxic products of microorganisms transfusion of the
wrong blood type or rh incompatibility of fetal and
maternal blood, a condition called erythroblastosis
• Fetalis.
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• LIFE SPAN & FATE OF RBC’S
• Average life span- about 120 days.
• Spleen- graveyard of red blood cells.
• Daily 10% red blood cells, which are senile, destroyed in
normal young healthy adults.
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ARTICLE HEMOLYTIC ANEMIA
Title Hemolytic anemia
Authors Tuchscherer A1, Chemnitz J.
Internist (Berl). 2015 Sep;56(9):1000-8
Abstract Hemolytic anemia can be caused by various hereditary o
acquired diseases. Classification is usually based on corpuscula
or extra corpuscular defects. Beside the anemia, laborator
testing indicates increased lactate dehydrogenase, unconjugate
bilirubin and reticulocytes as well as reduced or absent plasm
haptoglobin. Knowledge of further diagnostic procedures (e.g
Coombs test, schistocytes, hemoglobin electrophoresis or flow
cytometric analysis) leads in many cases to an underlying diseas
with differentiated therapeutic options. Autoimmune hemolyti
anemia (AIHA) is often associated with diseases as HIV
connective tissue disease, lymphomas or malignant tumors an
the hemolytic process is preexisting in many cases. Thromboti
microvascular diseases (e.g., thrombotic thrombocytopeni
purpura or hemolytic-uremic syndrome) are further importan
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• REFERENCES
• Guyton and hall text book of medical physiology 12th edition2011.
• Ganong review of medical physiology-23rd edition.
• K Sembulingam essentials of medical physiology-6rd edition.
• Text book of medical pathology 6th edition by Harsh Mohan.
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CONTE
NT
8. HEMOGLOBIN
9. BLOOD GROUPS
10. BLOOD TRANSFUSION
11. WBC’S (NEUTROPHIL, EOSINOPHIL, BASOPHIL,
LYMPHOCYTES, MONOCYTES)
• REFERENCES
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8. HEMOGLOBIN
• The red, oxygen carrying pigment in rbc is
hemoglobin.
• It consists of protein globin(polypeptide) united
with the pigment haeme(heme).
• Hemoglobin has ability to combine with oxygen
is due to four iron atoms asso. with each heme
group within the molecule.
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• STRUCTURE OF HEMOGLOBIN
• Heme
• It is an iron containing porphyrin.
• The iron in heme is in ferrous (fe2+) form.
• Each fe2+ combines loosely and reversibly with one
molecule of oxygen.
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• Globin:
• It is a protein built from 4 polypeptide chains, two
alpha and two beta chains.
•Of two alpha chains each contains 141 amino-
acids and of two beta-chains each contains 146
amino-acids.
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• FUNCTIONS OF HEMOGLOBIN
Transport of oxygen from lungs to the tissues.
Transport of co2 from the tissues to the lungs.
It acts as an excellent acid-base buffer, being a protein.
Is responsible for 70% buffering power of whole blood.
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• TYPES OF HEMOGLOBIN
1) Embryo HbP(Primitive)- (Α2Ε2)
2) Adult hemoglobin HbA- (Α2Β2)
3) Fetal hemoglobin HbF(before birth)- (Α2Γ2)
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• NORMAL VALUES OF HEMOGLOBIN
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Stage of life Value
At Birth 25 gm%
After 3rd Month 20 gm%
After 1 year 17 gm%
In adult Males 15 gm%
In Adult Female 14.5 gm%

• FORMATION OF HEMOGLOBIN
Synthesis of hemoglobin begins in the pro-erythroblasts
and continues even into the reticulocyte stage of the red
blood cells.
Therefore, when reticulocytes leave the bone marrow and
pass into the blood stream, they continue to form minute
quantities of hemoglobin for another day or so until they
become mature erythrocytes.
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• COMPOUNDS OF HEMOGLOBIN
Physiological
Oxyhemoglobin
Deoxyhemoglobin
Carbhemoglobin
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Pathological
Methemoglobin
Carboxyhemoglobin
Sulphemoglobin

ABNORMAL DERIVATIVES OF HEMOGLOBIN
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• TREATMENT FOR PATHOLOGICAL
VARIATIONS
1. For methemoglobin- blood transfusion; but only if small
amount of methemoglobin is present, then an enzyme called
methemoglobin reductase – present is rbc act on them &
eliminate them.
2. For carboxyhemoglobin- oxygen therapy
3. For sulphemoglobin- generally self limiting; sometimes blood
transfusion needed
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• DESTRUCTION OF HEMOGLOBIN
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9. BLOOD GROUPS
• DISCOVERED BY THE AUSTRALIAN SCIENTIST KARL
LANDSTEINER IN 1901.
Blood groups are determined by the presence of antigen in
RBC membrane.
When blood from two individuals is mixed, some times
clumping of RBC’s occurs. This clumping is because of
immunological reactions.
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• LANDSTEINER’S LAW
If a particular antigen is present in the RBC’s, corresponding
antibody must be absent in the serum.
If a particular antigen is absent in the RBC’s, the
corresponding antibody must be present in the serum.
• Landsteiner discovered two blood systems called ABO system
and RH system
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1. ABO
SYSTEM
Based on presence or absence of antigen A and antigen B
blood is divided in to four groups:
i. ‘A’ group
ii. ‘B’ group
iii. ‘AB’ group
iv. ‘O’ group
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• DETERMINATION OF ABO GROUP
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• ANTIGEN & ANTIBODY PRESENT IN BLOOD
GROUPS
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Group Antigen in RBC Antibody in
serum
A A Anti B
B B Anti A
AB A and B No antibody
O No antigen Anti A and AntiB

2. CDE BLOOD GROUP SYSTEM
• Out of C,D and E D is the strongest antigen.
• Also called rhesus(rh) system
• 85% of the population is - rh⁺
• If rh-d antigen is present in blood(rbc)
• Rh⁺
• If rh-d antigen is absent in blood(rbc),
• Rh⁻
• It is determined by anti-rh serum.
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10. BLOOD TRANSFUSION
• The process of receiving blood products into one's circulation
intravenously. Transfusions are used in a variety of medical
conditions in order to replace the lost components of the blood.
• Earlier used whole blood, but modern medical practice
commonly uses only components of the blood, such as red
blood cells, white blood cells, plasma, clotting factors, and
platelets.
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• TYPES OF BLOOD TRANSFUSION
a. Direct
b. Indirect
c. Auto-hemotransfusion
Rules for blood transfusion
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Precautions
while
Blood transfusion
BEFORE
No
communicab
le diseases
Matching ABO
& Rh
compatibility
DURING
Volume
overload
Metaboli
c side
effects
AFTER
Observation
for delayed
effects

• TYPES OF TRANSFUSION REACTIONS
A) Immune mediated hemolytic transfusion reactions:
1. Acute htrs: these are due to preformed antibodies against donor RBC
antigens present in the recipient’s blood. Non- ABO incompatibility
reactions due to minor recipient antibodies (anti-rh, anti-kidd or anti-jka)
tend to be milder and generally lead to extravascular hemolysis.
2. Delayed htrs: these are due to an anamnestic response to donor rbc
antigens which produces antibodies after a lag period of 3-10 days. This
requires prior sensitization in the form of pregnancy, transplantation or
transfusions.
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B) Non-immune-mediated hemolytic transfusion reactions
• These are generally related to improper storage and handling of blood
leading to hemolysis in vitro prior or during transfusion:
1. Thermal injury: during re-warming of the blood if temperatures reach
more than 42°C
2. Cold injury: inappropriate storage with exposure to ice or temperatures
less than 6°C
3. Mechanical injury: lysis during transfusion through small-bore catheters.
4. Infection
5. Concomitant drug-induced hemolysis
6. Concomitant administration of hypotonic solution leading to osmotic
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• RH INCOMPATIBILITY
• In blood transfusion :
•Rh⁻ person cannot receive blood from rh⁺ person, whereas
rh⁺ person can receive blood from rh⁻ person without any
problems.
• If a rh⁻ person receive blood from rh⁺ person for the first
time, due to this exposure, there will be formation
antibodies(anti-rhd)
• So, if a second transfusion is done again with rh⁺ blood,
then, the antibodies which are already present causes
clumping.
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• Erythroblastosis fetalis :
• If a rh⁻ mother carry a rh⁺ fetus, due to placental barrier the
blood doesn’t mix. However during delivery some rh⁺ from
fetus reaches mother.
• So, the mother will start producing antibodies against rh⁺ .
during consecutive pregnancies, this may cause destruction
of rbcs in the fetus causing hemolytic
anemia(erythroblastosis fetalis). So after each pregnancy,
the mother will receive anti-RhD (prophylaxis)to prevent this
incompatibility.
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• COMPLICATIONS OF BLOOD TRANSFUSION
1. Transfusion reactions
2. Transmission of diseases
3. Reaction caused by massive transfusion
4. Complication of IV fluid administration
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1. TRANSFUSION REACTIONS- INCOMPATIBILITY, ALLERGIC
REACTIONS, SENSITIZATION TO LEUCOCYTES &
PLATELETS.
2. TRANSMISSION OF DISEASE- HEPATITIS, AIDS,
BACTERIAL INFECTIONS.
3. REACTIONS CAUSED BY MASSIVE TRANSFUSION- ACID
BASE IMBALANCE, HYPERKALEMIA, HYPOTHERMIA.
4. COMPLICATION OF GENERAL IV FLUID
ADMINISTRATION- THROMBOEMBOLISM AIR EMBOLISM.
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• 11. WBC’S
• The WBC’s, also called as
leucocytes, are the mobile units of
the body’s protective system.
• They are formed partially in the
bone marrow (granulocytes
and monocytes and a few
lymphocytes) and partially in the
lymph tissue (lymphocytes and
plasma cells).
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• After formation, they are transported in the blood
to different parts of the body where they are
needed.
• The real value of the white blood cells is that most
of them are specifically transported to areas of
serious infection and inflammation, thereby
providing a rapid and potent defense against
infectious agents.
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• MORPHOLOGY WBC
• Have nuclei
• Size: 9-12 µ
• Approximately1% of total blood volume in healthy adult.
• They Live for around 3-4 days
• Normal Count: 5000-10,000/cubic millimeter
• Infants: 20,000/ cc mm
• Children: 10,000- 15,000/ cc mm
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• FUNCTIONS OF WBC’S
• Major function is protective function.
• Provides immunity and defends the body against
foreign bodies.
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• FORMATION OF WBCS
• Called as leucopoiesis
• Formed in bone marrow
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• TYPES OF LEUCOCYTES
• Granulocytes : Neutrophil
Basophil
Eosinophil
• Agranulocytes : Monocyte
Lymphocyte
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Differential count
Neutrophils 62.0%
Eosinophils 2.3%
Basophils 0.4%
Monocytes 5.3%
Lymphocytes 30.0%

• LIFESPAN OF
WBC
• NEUTROPHILS : 2-5 DAYS
• EOSINOPHILS: 7-12 DAYS
• BASOPHILS: 12-15 DAYS
• MONOCYTES: 2-5 DAYS
• LYMPHOCYTES: 1 DAYS
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1. NEUTROPHILS
• Size - 10-14 microns in diameter
• Nucleus
• Purple in colour
• Multilobed (1-6 lobes), that is why also
called polymorphonuclear leucocyte. More
the number of lobes, the more mature is
the neutrophil.
• Cytoplasm: slight bluish in colour, granular.
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• Granules
(i)'Fine' sand like particles:- called 'pinpoint' granules.
(ii)'Neutrophilic' in nature (red-brown in colour), i.E. Take both the acidic
and basic stains, therefore, it is called a neutrophil
(iii)Also contain varieties of enzymes. They can 'lyse' any type of
substance, the granules are thus regarded as lysosomes.
• Important in inflammatory response-phagocytes that engulf bacteria
and debris.
• First line of defense (first cells that come to the area of inflammation).
• Multi functional cells that attack and destroy viruses and bacteria.
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NEUTROPHILIA
• Means increased in neutrophil count.
Causes are: a) Pathological b) Physiological
1. Acute infections 1. Exercise
2. Inflammatory conditions 2. Food intake
3. Acute hemolysis 3. Emotion, stress
4. Metabolic conditions
5. Poison by insect venom
6. After acute hemorrhage
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NEUTROPENIA
• Decreased count of neutrophils
• Causes-
1. Bone marrow dysfunction
2. Toxins(alcohol, benzene)
3. Immune dysfunction
4. Starvation
5. Medication(antibiotic therapy, chemotherapy, anticonvulsants)
6. Radiation
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• NEUTROPHILS & MACROPHAGES DEFENDS
AGAINST MICROORGANISMS
• DIAPEDESIS
• MOVE THROUGH TISSUE SPACES BY
AMEBOID MOTION.
• ATTRACTED TO INFLAMED TISSUE AREAS
BY CHEMOTAXIS
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2. EOSINOPHILS
• Size: 10-14 microns in diameter
• Nucleus:
• Purple colour, Usually bilobed, the two lobes are connected with chromatin thread
thus producing 'spectacle' appearance.
• Cytoplasm: is acidophilic therefore appears light pink in colour.
• Granules- Coarse; stains bright red with acidic dye.
They contain:
Eosinophil peroxidase– Destroys worms
Bacteria and tumor cells
Major basic protein – destroys parasites
Eosinophil cationic protein – major destroyer of worms and parasites.
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FUNCTIONS OF EOSINOPHIL
• Mild phagocytosis because less motile than neutrophils.
• Eosinophils collect at the sites of allergic reactions.
• Eosinophils attack parasites that are too large to be engulfed by phagocytosis
• Eosinophil granules release chemicals which are toxic to larvae of parasites.
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• Eosinophilia: i.e. Increase in eosinophils
Causes
• Allergic conditions e.g. Bronchial asthma
• Parasitic infestation e.g. Worms.
• Skin diseases
• Eosinopenia: i.e. Decrease in eosinophils
• Seen after injection of corticosteroids
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3. BASOPHILS
• 0.5% of the wbc’s
• Important in allergic reactions heparin helps clear fat from blood.
Size:10 – 14 microns in diameter
Nucleus: as in eosinophils.
Cytoplasm: slight basophilic, therefore, appears blue; granular.
Granules:(I) coarse; stains purple or blue with basic (methylene
blue) dye.
• (Ii) granules are plenty in number and overcrowd the nucleus
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FUNCTIONS OF BASOPHILS
• Mild phagocytosis
• Liberates heparin which acts as anticoagulant and keeps the blood in
fluid state in the body.
• Proteases and myeloperoxidase: these enzymes exaggerate the
inflammatory responses.
• Cytokine: IL-4 accelerates inflammatory response
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Basophilia: i.e. Increase in basophils.
• Causes
Chickenpox
Smallpox
Tuberculosis
Influenza
Basopenia: i.e. Decrease in basophils.
• Causes
After administration of glucocorticoids.
Drug induced reactions.
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4. LYMPHOCYTES
• 25-33 % of the wbc's
• B-lymphocytes: produceantibodies
• T-lymphocytes:
• Directly destroy virus- invaded cells and cancer cells
• Types of Lymphocytes
• Large lymphocytes: 10-14 microns in diameter: precursor of small lymphocytes.
• Small lymphocytes : 7-10 microns in diameter; responsible for antibody production
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NUCLEUS
• Single; very big; purple in colour.
• Shape: round, oval or indented.
• Central in position and occupies whole of the cell leaving marginal cytoplasm at one
end of it or all around it.
• Nuclear chromatin is coarse and lumpy (shapeless).
• Cytoplasm-pale blue
• Scanty, its amount is always less than the amount of the nucleus
Functions:
• Produce antibodies, immune substances, specially in delayed hypersensitivity
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Lymphocytosis i.e. Increase in lymphocytes.
• Causes
In children lymphocytes (60%) are more than neutrophils (40%), called
relative lymphocytosis.
Chronic infections e.g. Tuberculosis (TB).
Lymphatic leukaemia.
Viral infections.
Lymphopenia i.e. Decrease in lymphocytes.
• Causes
Hypoplastic bone marrow
AIDS
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5. MONOCYTES
• 2-6 % of the wbc’s.
• Exit blood (diapedesis)
• To become macrophages
• Phagocytic = defend against viruses and bacteria
Size: 10-18 microns in diameter with irregular cell outline.
Nucleus: single, pale staining.
• Round or indented (kidney shaped).
• Eccentric in position i.e. Present on one side of the cell.
• Nuclear chromatin is finely reticular.
Cytoplasm: usually pale blue; clear.
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Monocytosis: increase in monocytes
• Causes
Tuberculosis
Syphilis
Some leukemia’s.
Monocytopenia: decrease in monocytes.
• Cause:
Hypoplastic bone marrow.
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• REFERENCES
Guyton and hall text book of medical physiology
12th edition 2011.
Ganong review of medical physiology-23rd edition.
K sembulingam essentials of medical physiology-6rd
edition.
Textbook of oral and maxillofacial surgery by nelima
anil malik 2nd edition.
Shafer”s textbook of oral pathology 6th edition.
A manual on clinical surgery by s das 10th edition.
1/13/2019 91

• CONTENT
12. PLATELETS
13. HEMOSTASIS
14. BLOOD COAGULATION
15. LOCAL HEMOSTATIC AGENTS
16. ANTICOAGULANTS FOR CLINICAL USE
17. LABORATORY INVESTIGATIONS
19. REFERENCES
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12. PLATELETS OR THROMBOCYTES
Structure- (Platelets = small plate; thrombo- lump or clot; cytes- cells)
General features: Platelets are the smallest blood cells, colourless,
spherical, oval or rounded granulated bodies
-2.5 microns in diameter with an average volume 7.5 cubic microns.
-Leishman staining shows a faint blue cytoplasm with distinct
-Reddish purple granules; nucleus is not present
1/13/2019K Sembulingam Essentials of Medical Physiology-6rd
edition.
95

CYTOPLAS
M
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I. Golgi apparatus, endoplasmic reticulum, mitochondria, microtubule, micro vessels,
filaments and different types of granules.
II. Protein- myosin and actin(resp for contraction of platelet)
III. Protein named thrombosthenin for clot retraction
IV. Von willebrand factor for adherence of platelets
V. Fibrin stabilizing factor
VI. Platelet derived growth factor- repair of damaged blood vessels
VII. Platelet activating factor- aggregation of platelets during injury of blood vessels.
VIII. Enzymes like ATP and enzymes for synthesis of prostaglandins
IX. Hormonal substance like histamine and adrenaline
X. Other chemical substances like glycogen, blood group antigens and in organic
substances like calcium, copper, magnesium and iron.

• FORMATION OF PLATELETS
• Development of platelets
• Site of origin : Bone marrow
Pluripotent stem cell
Committed stem cell (polyploid precursor cell)
Megakaryoblast (stage I)
Pro-megakaryocyte (stage II)
Granular megakaryocyte (stage III)
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• FUNCTIONS OF PLATELETS
1. ROLE IN BLOOD Clotting- platelets are responsible for the formation of intrinsic
prothrombin activator. This substance is responsible for the onset of blood clotting
2. ROLE IN CLOT RETRACTION- Cytoplasm of platelets contains the
contractile proteins, namely actin, myosin and thrombosthenin, which are
responsible for clot retraction.
3. ROLE IN PRESERVATION OF BLOOD LOSS-.Due to the adhesive property, the
platelets seal the damage in blood vessels like capillaries. By formation of
temporary plug.
4. ROLE IN REPAIR OF RUPTURED BLOOD VESSELS- Platelet-derived growth
factor (PDGF) formed in cytoplasm of platelets is useful for the repair of the
endothelium and other structures of the ruptured blood vessels.
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• Normal count is 1.5 to 4 lacs/ cu mm (average: 2.59 lacs/ cu mm). Its
count is very much constant.
• The circulating platelets represent approx. 60-75% of the platelet pool of
the body, the remaining are mostly in the spleen. Therefore, spleen acts as
a reservoir of platelets.
• Life span: 8-12 days.
• Destruction: mainly in the spleen. In hypersplenism (overactivity of
spleen), the platelets may almost disappear from circulation
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Thrombocytosis i.e. Increase in platelet count.
Causes:
• After administration of epinephrine due to splenic contraction.
• After trauma e.g. Surgery, injury, child birth etc.
• Splenectomy (removal of spleen)
• Stress - causes increased epinephrine release resulting in spleen
contraction.
• Hemorrhage
• Allergic condition
Thrombocytopenia i.e. decrease in platelet count.
Causes:
• Bone marrow depression.
• Splenomegaly
• Viral infection e.g. Dengue fever (particularly attacks platelets).
• Aplastic and pernicious anemia
• Acute infections
• Typhoid
• Tuberculosis
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Activated Platelets Inactive Platelets

• DISEASES INVOLVING BLOOD PLATELETS
a) Purpura: purplish discoloration of the skin and mucous membranes due to the
spontaneous extravasation of blood and it self as a symptoms rather then a disease
entity.
Nonthrombocytopenic purpura
Thrombocytopenic purpura
1. Primary
2. Secondary
b) Thrombocythemia: Increase in the number of circulating blood platelets.
c) Thrombosis: Formation of blood clot inside blood vessels - obstruct the blood flow.
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d) Von Willebrand disease: Is the most common hereditary blood-clotting
disorder in humans. An acquired form can sometimes result from other
medical conditions. It arises from a deficiency in the quality or quantity
of von willebrand factor (vwf).
e) Aplastic Anemia: Is a rare disease in which the bone marrow and
the hematopoietic stem cells that reside are damaged.
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• EVENTS IN
HEMOSTASIS
A. VASCULAR CONSTRICTION
B. FORMATION OF A PLATELET PLUG
C. FORMATION OF A BLOOD CLOT
D. EVENTUAL GROWTH OF FIBROUS
TISSUE
1/13/2019Guyton and Hall Text book of medical physiology 12th edition 2011 105

A. VASCULAR CONSTRICTION
(1) Local myogenic spasm
(2) Local autacoid factors from the traumatized tissues and
blood platelets
(3) Nervous reflexes.
1/13/2019
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106

B. FORMATION OF PLATELET PLUG
When platelets come in contact with a damaged vascular surface, change their
shape.
They begin to swell; they assume irregular forms
• With numerous irradiating pseudopods protruding from their surfaces.
• Their contractile proteins contract forcefully and cause the release of granules that
contain multiple active factors; they become sticky so that they adhere to collagen in
the tissues and the protein
• Called von Willebrand factor that leaks into the traumatized tissue from the plasma.
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C. FORMATION OF BLOOD CLOT
• Is the process by which blood changes from a liquid to a gel, forming
a blood clot.
• The mechanism of clotting involves activation, adhesion, and
aggregation of platelets along with deposition and maturation of fibrin.
D. Eventual Growth of Fibrous tissue
into the blood clot to close the opening in blood vessel permanently.
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14. BLOOD
COAGULATION
The clot begins to develop in 15 to 20
seconds of the trauma to the vascular
wall has been severe, and in 1 to 2
minutes if the trauma has been minor.
Activator substances from the
traumatized vascular wall, from
platelets, and from blood proteins
adhering to the traumatized vascular
wall initiate the clotting process
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MECHANISM OF BLOOD COAGULATION
More than 50 important substances that cause or affect blood
coagulation have been found in the blood and in the tissues.
Some that promote coagulation are called procoagulants,
and others that inhibit coagulation are called
anticoagulants.
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Prothrombin activator is generally
considered to be formed in two ways:
By the extrinsic
Pathway that begins with trauma to the
vascular wall and surrounding tissues.
By the intrinsic
• Pathway that begins in the blood itself.
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INTRINSIC & EXTRINSIC PATHWAY
• After blood vessels rupture clotting occurs by both pathways.
• Extrinsic pathway can be explosive, once initiated clotting can occur in
as little as 15 seconds.
• Intrinsic pathway is much slower to proceed usually requiring 1 to 6
minutes to cause clotting.
Within a few minutes after a clot is formed, it begins to contract and
usually expresses most of the fluid from the clot within 20 to 60 minutes.
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EXTRINSIC PATHWAY
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INTRINSIC PATHWAY
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FIBRINOLYSIS
Lysis of blood clot inside the blood vessel is called fibrinolysis.
This occurs by a substance called fibrinolysin /plasmin
• Significance- Allows reopening of affected blood vessels and
prevents development of infarction.
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CONDITIONS CAUSING EXCESSIVE BLEEDING
IN HUMANS
1. Vitamin k deficiency
2. Von Willebrand's disease
3. Para hemophilia
4. Hypofibrinogenemia
5. Fibrin-stabilizing factor deficiency
6. Thrombocytopenia
7. Hemophilia
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15. LOCAL HEMOSTATIC MEASURES
• A. MECHANICAL METHODS
PRESSURE GELFOAM
USE OF HEMOSTATES OXYCEL
SUTURE & LIGATION THROMBIN
FIBRIN GLUE
ADRENALIN
CAUTERY WHOLE BLOOD
CRYOSURGERY FRESH FROZEN PLASMA
ELECTROSURGERY CROPRECIPITATE
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B. CHEMICAL METHODS
C. THERMAL AGENTS
D. SYSYEMIC AGENTS

GELFOAM
• Gelfoam (pharmacia) is one of commonly employed agents for the control of minor
bleeding. It is a porous, pliable sponge made from dried and sterilized porcine skin
gelatin. Gelfoam’s mode of action is not completely understood, but unlike collagen, it is
believed to be related to formation of a mechanical matrix that facilitates clotting rather
than affecting the blood-clotting mechanism. This agent can retain in its interstices 45
times its weight in blood. Gelfoam liquefies in one week and is completely resorbed in 4
to 6 weeks.
Its use is not associated with excessive scar formation. reported adverse reactions are
giant cell granuloma and hematoma formation, foreign body reactions, excessive
fibrosis, toxic shock syndrome, fever, and failure of absorption.
1/13/2019 119

BONE WAX
• Bone wax (ethicon) is a sterile mixture of beeswax, paraffin, and isopropyl palmitate (a
softening agent) that is packaged in individual foil envelopes. It is useful when bleeding
is from a visualized local vascular channel within bone, commonly referred to as a “bone
bleeder,” at the surgical site. This occurs commonly during the extraction of mandibular
third molars, and if not adequately addressed during surgery can be a reason for
postoperative bleeding
• Bone wax is non resorbable, and due to its possible adverse effect on
osteogenesis, caution should be used where regeneration of bone is expected (eg, a
future implant site). Mild inflammatory reactions have been reported in tissues adjacent
to the site of bone wax implantation, and this agent may prevent the clearing of bacteria
from infected sites.
1/13/2019 121

COLLAGEN BASED PRODUCTS
• Hemostatic collagen products are derived from either bovine tendon Or
bovine dermal collagen and are non-toxic and non-pyrogenic and to
control capillary, venous, and small arterial bleeding. It must be used dry
without addition of saline or thrombin.
• Surgicel can cause temporary sensory disturbances.
• Absorption of surgicel will occur in approximately 4-8 weeks. It should Not
be used (1) in closed spaces because of swelling, (2) on bony
defects(Fractures) as it may interfere with bone regeneration, and for
Control of hemorrhage from large arteries.
1/13/2019
SANTHOSH KUMAR MP* LOCAL HEMOSTATIC AGENTS IN THE MANAGEMENT OF BLEEDING IN ORAL SURGERY
asian journal of pharmacology & research vol 9, issue 3, 2016 123

• Adverse reactions include:(1) encapsulation of fluid and foreign
body reaction, if the product Is left in the wound, (2) stenosis of
vascular structures if cellulose is used to wrap a vessel tightly,
(3) burning sensation when placed in unanesthetized nasal
passages. Excessive amounts of the material should be
removed if possible to prevent delayed healing, (4) surgical
Granulomas, and (5) neurological complications.
1/13/2019 124

ABSORBABLE HEMOSTAT COLLAGEN SPONGE
• It is collagen derived from purified and lyophilized (i.E., Freeze-dried)
Bovine flexor tendon and is available as soft, white, pliable, non-friable,
coherent, sponge-like structures. The products are highly absorbent and
able to hold many times their own weight of fluid. Their indications are for
wound protection and for control of oozing or bleeding from clean oral
wounds. As for application, these products should be held in place for
approximately 2-5 minutes to achieve hemostasis and then may be
removed, replaced, or left in situ. Because absorbable collagen
hemostatic sponges do not disperse-like microfibrillar collagen does,
these products are easier to handle and place.
1/13/2019

• It must be handled dry, only the amount necessary to be used and excess
must be removed. All of these collagen materials are completely resorbed
within 14-56 days. In addition to serving as a mechanical obstruction to
bleeding, these materials affect the coagulation process. In contact with
blood, collagen causes aggregation of platelets, which bind in large
numbers to the collagen fibrils. The aggregated platelets degranulate,
releasing factors such as thromboxane A2 that assist in the formation of a
clot.
1/13/2019

ACTCEL
• It is a new topical hemostatic agent made from treated and sterilized
cellulose, available as meshwork-like surgicel. On contact with blood,it
expands 3-4 times its original size and gets converted into gel. It
dissolves completely in 1-2 weeks into biodegradable end products
Glucose and water and does not affect wound healing.
• Actcel’s mechanisms of action are multiple, enhancing the coagulation
process biochemically by enhancing platelet aggregation and physically
by 3D clot stabilization. It is used in third molar sites and supposed to
prevent dry sockets. Furthermore, it is used in periodontal and
orthognathic surgeries.
1/13/2019

• It is indicated for
• The control of bleeding from open wounds and body cavities (e.G.
Mouth,Ears, nose, throat, and vagina) and does not contain chemical
additives, thrombin, or collagen and is hypoallergenic. Another special
characteristic of this material is its bacteriostatic properties, which are
especially important in contaminated wounds or in body cavities, in which
it is difficult or impossible to maintain a sterile field. Gelitacel is a fast-
working, oxidized resorbable cellulose hemostatic gauze of natural origin
made from highest alpha-grade selected cotton. It resorbs as quick as 96
hrs, therefore giving it decreased risk for encapsulation.
• Gelitacel is cheaper than surgicel
1/13/2019

FIBRIN SEALANTS
• Fibrin sealant is a natural or synthetic combination hemostatic agent and also tissue
adhesive which has an impact on angiogenesis and wound healing. Fibrin sealants are
usually comprised fibrinogen (factor 1a),Fibrin-stabilizing factor, thrombin (factor 2a),
and aprotinin 2 and when applied to the surgical site forms a fibrin clot. These products
can be applied using a syringe-like applicator or sprayed over a larger area using a gas-
driven device. It can be used in bone grafting procedures particularly sinus lift surgery.
• It is contraindicated in patients who are sensitive to bovine proteins. An excessively thick
sealant layer may prevent revascularization at the surgical site, causing tissue necrosis.
1/13/2019

ALUMINUM DERIVED HEMOSTAT(BIOGLUE)
• Tissue adhesives have been used widely for decades, for both their
• Hemostatic and sealant properties. The main disadvantage of bioglue is
• That it can leak through suture tracks.
1/13/2019

CHITOSAN BASED PRODUCTS
• Polymers containing n-acetyl glucosamine include hyaluronic acid, Chitin,
and chitosan. Chitosan has been recognized as the most effective of
these for local hemostasis. Chitosan is a naturally occurring,
Biocompatible, electro-positively charged polysaccharide that is derived
from shrimp shell chitin. This charge attracts the negatively charged red
blood cells forming an extremely viscous clot, which seals the wound and
causes hemostasis. Chitosan enhances hemostasis by interacting with
cellular components forming a cellular lattice that entraps cells to form an
artificial clot.
1/13/2019

THROMBIN
• Topical thrombin products are derived from either bovine or human
Plasma, or they are manufactured using recombinant DNA techniques
(i.e., Recombinant thrombin). Thrombin may be used topically as a dry
powder, as a solution for use with gelatin sponges, mixed with a gelatin
matrix, or as a spray. It has a rapid onset of action (e.g., Within 10
minutes). It converts fibrinogen to fibrin. It is commonly used with
Gelfoam to treat moderate to severe bleeding. Thrombin should never be
injected into the bloodstream or allowed to enter the bloodstream through
large, open blood vessels because it can cause extensive intravascular
clotting which can be fatal.
1/13/2019

TRANEXAMIC ACID
• Tranexamic acid is an antifibrinolytic agent that stabilizes clots and
facilitates clot formation by competitively inhibiting plasminogen, the
enzyme responsible for activating plasmin. The main role of plasmin in
the body is clot degradation or fibrinolysis; hence, Tranexamic acid non-
competitively inhibits plasmin and stabilizes clot formation. Oral
tranexamic acid has been shown to be beneficial in the management of
patients with both inherited and acquired bleeding diatheses undergoing
minor oral surgeries. It can also be useful as a prophylactic mouthwash in
patients who are on anticoagulant medications which require oral surgery.
1/13/2019

HEMOSTATIC SOLUTIONS
• Styptics
Styptics, e.g., Aluminum solutions when applied locally cause hemostasis by contracting
tissue to seal injured blood vessels.
• Tannic acid
Tannic acid is a commercial compound that is similar to the plant Polyphenol tannin,
which stops bleeding from mucous membrane via Vasoconstriction.
• Lysine analogs
Tranexamic acid, epsilon-aminocaproic acid
1/13/2019

TOPICAL THROMBIN AGENTS
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16. ANTICOAGULANTS FOR CLINICAL USE
1. Heparin: as intravenous anticoagulant
• Relatively small quantity injected: 0.5-1 mg/kg of weight( increases blood clotting time
by 6-30 minutes
• The action of heparin lasts about 1.5 to 4 hours. The injected heparin is destroyed by
an enzyme in the blood known as heparinase.
2. Coumarins: When a coumarin, such as warfarin, is given to a patient, the plasma levels
of prothrombin and factors VII, IX, and X, all formed by the liver, begin to fall, indicating
that warfarin has a potent depressant effect on liver formation of these compounds.
• Warfarin causes this effect by competing with vitamin k.
• Normal coagulation usually returns 1 to 3 days after discontinuing coumarin therapy.
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17. LABORATORY INVESTIGATIONS
1) BLEEDING TIME (BT)
2) CLOTTING TIME (CT)
3) PROTHROMBIN TIME (PT)
4) PARTIAL THROMBOPLASTIN TIME
(PTT)
5) THROMBIN TIME (TT)
1/13/2019
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1) BLEEDING TIME
• PROVIDES ASSESSMENT OF PLATELET COUNT &
FUNCTION
• NORMAL VALUE: 3-6 MIN
• PROLONGED BT: CONGENITAL & ACQUIRED DISORDERS
OF PLATELET FUNCTION
THROMBOCYTOPENIA
PURPURA
VON WILLEBRAND DISEASE
1/13/2019
146

• Dukes method: with the duke method, the patient ispricked with a
special needle or lancet, preferably on the earlobe or fingertip,
after having been swabbed with alcohol. The prick is about 3–4
mm deep. The patient then wipes the blood every 30 seconds
with a filter paper. The test ceases when bleeding ceases.
1/13/2019
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2) CLOTTING TIME
• NORMAL VALUE: 4-9 MIN
• PROLONGED CLOTTING TIME: HEMOPHILIA
• METHOD: CAPILLARY GLASS METHOD
1/13/2019
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3) PROTHROMBIN TIME
• MEASURES EFFECTIVENESS OF EXTRINSIC PATHWAY
• PROLONGED PROTHROMBIN TIME: VITAMIN K DEFICIENCY
PROTHROMBIN FACTOR
DEFICIENCY
• NORMAL VALUE: 12-15 SEC
1/13/2019
149

• Prothrombin time is commonly measured using
blood plasma.
• Blood is drawn into a test tube containing liquid
citrate.
• Blood is mixed & then centrifuged to separate
blood cells from plasma.
• Tissue factor- thrmboplastin is then added and
clotting time is checked.
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4) PARTIAL THROMBOPLASTIN TIME
• Measures effectiveness of intrinsic pathway & measures
coagulation disorders
• Normal value: 25-40 seconds
• Prolonged PTT-
• Factor III deficiency
• Increases in hemophilia
• Anticoagulation with heparin
1/13/2019 151

METHOD
• Blood samples are collected in tubes with oxalate or citrate to arrest
coagulation by binding to calcium. In order to activate the intrinsic
pathway, phospholipid, and activator(such as silica, kaolin, ellagic
acid), and calcium (to reverse the anticoagulant effect of the oxalate)
are mixed into the plasma sample. The time is measured until a
thrombus (clot) forms.
1/13/2019 152

5) THROMBIN TIME
• It measures the rate of conversion of fibrinogen to fibrin
• Normal value: 9-13 seconds
• Prolonged TT- contamination with heparin or acquired liver diseases
• Method-
After liberating the plasma from the whole blood by centrifugation, bovine thrombin is
added to the sample of plasma.
The clot is formed and is detected optically or Mechanically by a coagulation
instrument.
The time between the addition of the thrombin and the clot formation is recorded as
the thrombin clotting time
1/13/2019 153

1/13/2019 154
Title Evaluation and association of serum iron and ferritin levels in
children with dental caries.
Author Venkatesh Babu NS, et al.
Journal J Indian Soc Pedod Prev Dent. 2017 Apr-Jun.
Level of evidence IV
Aim The aim of the study is to explore an association between
dental caries and serum levels of iron and ferritin in children
aged 3-12 years
Methods The study group included 120 children, hospitalized for
uncomplicated medical problems. Blood reports were evaluated
to determine serum iron and ferritin levels. Dental caries
experience was assessed using deft index.
Result Out of 120 children, 38 children showed low serum iron levels of which
31 children had dental caries and nine out of 15 children in the high
serum iron level group showed dental caries. High ferritin levels were
seen in three children among which two children were caries-free and
only one child had a low ferritin level who also had a positive deft
score
Conclusion Based on the results, it was concluded that there is an inverse
association between serum iron levels and dental caries
whereas there is no association between serum ferritin levels
and dental caries.

THE BLOOD YOU DONATE GIVES
SOMEONE ANOTHER CHANCE AT LIFE
GIVE THE GIFT OF LIFE
DONATE BLOOD
1/13/2019 155

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