PHYSIOLOGY

LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS

DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA

o Enzymes that synthesize prostaglandins

OUTLINE o Fibrin stabilizing factor
o Growth factor – causes vascular endothelial
I. Introduction A. Decreased Factors cells, vascular smooth muscle cells, and
A. Definition of Caused By Vitamin fibroblasts to multiply and grow
Hemostasis and K Deficiency
Platelets B. Hemophilia A. Hemostasis Events
B. Hemostasis Events II. Thrombocytopenia
III. Thromboembolic 1. Vascular Constriction - ↓ blood loss after vessel
rupture
II. Mechanism of blood Conditions
coagulation A. Thormbo & Emboli A. Local Myogenic Spasm - contributes more to
A. General Mechanism B. Causes of vasoconstriction initiated by direct damage to
B. Prothrombin to Thromboembolic vascular wall
Thrombin Conditions B. Local autacoid factors from traumatized
C. Fibrinogen to Fibrin – C. Use of t-PA (Tissue tissues and blood platelets
Formation of Clot Plasminogen  Small Blood Vessels → release
D. Blood Coagulation Activator) endothelin
Sequential Pathways D. Conditions  Platelets → release Thromboxane A2
E. Intravascular IV. Anticoagulants for (vasoconstrictor)
Anticoagulants Clinical Use C. NERVOUS REFLEXES – initiated by pain nerve
F. Plasmin Causes Lysis A. Heparin impulses and sensory impulses from traumatized
of Blood Clots B. Coumadin vessels and nearby tissues
III. Conditions that V. Prevention of Blood
cause excessive Coagulation Outside
bleeding in humans the Body
VI. Blood Coagulation
Tests

I. Introduction

A. Definition of Hemostasis and Platelets

HEMOSTASIS – is the prevention of blood loss;
literally means “STOP BLEEDING” Fig. 1 Local Vasoconstriction
PLATELETS (THROMBOCYTES) 2. Formation Of Platelet Plug – seals small cuts and
 Originate from MEGAKARYOCYTES which fragment small vessel holes instead of usual blood clot
into small platelets in the BONE MARROW or in the
periphery
 NORMAL COUNT: 150,000 – 300,000/µL; lasts 8 to
12 days
 NO NUCLEI; does not reproduce itself
 Glycoproteins in the cell surface prevents adhesion to
normal endothelium but makes it adhere to damaged
tissues especially to exposed collagen fibers
 Eliminated from the circulation by macrophage
system or by macrophages in the spleen
 ACTIVE FACTORS:
o Contractile proteins: actin, myosin and
thrombasthenin
o Residuals of ER and golgi apparatus that store
Ca++ and synthesize various enzymes
o Mitochondria that synthesize ATP and ADP

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 PHYSIOLOGY
LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS
DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA

Table 1: Clotting factors and their symptoms

Fig. 2 Platelet aggregation on the damaged blood vessel

CLOT RETRACTION
 Clot contracts and expresses most of its fluid within
20 to 60minutes
 fluid expressed is serum
 Platelets are essential/necessary for clot retraction to
occur
o Bonds fibrin monomers together
o Release pro-coagulants : fibrin stabilizing factor
o Contributes directly to contraction thru activation
of actin, myosin, thrombasthenin
 Retraction is activated by thrombin and Ca++(Ca++
coming from ER, GA, mitochondria of platelets
Fig. 3 Mechanism of Platelet aggregation
 Retraction pulls edges of broken blood vessels 
3. FORMATION OF BLOOD CLOT DUE TO BLOOD contributes further to state of hemostasis
COAGULATION
4. EVENTUAL GROWTH OF FIBROUS TISSUE TO
 Activator substance from traumatized vascular
PERMANENTLY CLOSE THE BLOOD VESSEL
walls and adhered platelets and blood proteins –
HOLE
INITIATE CLOTTING PROCESS
 Severe vasular trauma – 15 to 20 secs
 Minor trauma – 1 to 2 mins
 After 3 to 6 mins - opening is filled with clot
 Within 1 hour – clot retracts to further close the
opening

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 PHYSIOLOGY
LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS
DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA

point, because these terminal steps normally occur

II. Mechanism of Blood Coagulation rapidly to form the clot

o Platelets also play an important role in the

A. General Mechanism conversion of prothrombin to thrombin
because much of the prothrombin first
attaches to prothrombin receptors on the
Rupture of vessel/ damage to blood itself platelets already bound to the damaged
↓ tissue
Formation of complex activated factor called prothrombin
activator Prothrombin
↓  A plasma protein and a alpha2-globulin.
Conversion of prothrombin into thrombin by prothrombin
 Unstable that split easily into thrombin and other
activator
compounds.
↓
 Continually formed in liver and constantly used
Conversion of fibrinogen into fibrin fibers that enmesh
throughout the body for blood coagulation
platelets, blood cells and plasma by thrombin
 Vitamin K is required by the liver for normal activation
of prothrombin as well as other clotting factor
B. Prothrombin to Thrombin o Microflora in gut produce Vitamin K.
o Thus, newborns are injected with Vitamin K
because their gut is still sterile.
o Therefore, either Vitamin K deficiency or liver
disease prevents normal prothrombin formation.

Fig. 4 Schema for conversion of prothrombin to thrombin

and polymerization of fibrinogen to form fibrin fibers

Prothrombin activator is formed as a result of rupture of

a blood vessel or as a result of damage to special
substances in the blood.
↓
The prothrombin activator, in the presence of sufficient Fig. 5 Role of Vitamin K in Blood Coagulation
amounts of ionic Ca++, causes conversion of
prothrombin to thrombin C. Fibrinogen to Fibrin – Formation of clot
↓
Fibrinogen
The thrombin causes polymerization of fibrinogen
molecules into fibrin fibers within another 10 to 15  Formed in the liver.
seconds. o Liver disease can decrease plasma
concentration of fibrinogen as pointed out with
The rate – limiting factor is formation of prothrombin prothrombin.
activator and not the subsequent reactions beyond that

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 PHYSIOLOGY
LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS
DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA
o It has high molecular weight thus, little fibrinogen
normally leaks from blood vessels into the
interstitium.
 This is why interstitial fluid do not normally
coagulate.
Thrombin
 A protein enzyme with weak proteolytic capabilities.
 Removes four lov-molecular weight peptides on
fibrinogen forming one molecule of fibrin monomer
Fibrin
 Has the automatic capability to polymerize other
fibrin monomers to form fibrin fiber.
 Forms many long fibrin fibers in seconds that
constitute the reticulum of the blood clot
 Fibrin monomers are held together by hydrogen
bonds and new forming fibers are not cross – linked
to each other.
 Fibrin – stabilizing factor – greatly strengthen the
fibrin reticulum.
 Released by the trapped platelets in the clot
 Activated by thrombin then, once activated causes
Fibrin – stabilizing factor causes covalent bonds to
form between fibrin monomers
Blood Clot
 composed of a meshwork of fibrin fibers running in
all directions and entrapping blood cells, platelets,
and plasma.
 fibrin fibers also adhere to damaged surfaces of
blood vessels; therefore, the blood clot becomes
adherent to any vascular opening and thereby
prevents further blood loss.
 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.
 The fluid expressed is called serum because all its
fibrinogen and most of the other clotting factors
have been removed;
Fig. 6 Blood Clot formation
 Platelets are essential/necessary for clot retraction
to occur
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o Bonds fibrin monomers together
o Release pro-coagulants : fibrin stabilizing
factor
o Contributes directly to contraction thru
activation of actin, myosin, thrombasthenin
 Retraction is activated by thrombin and
Ca++(Ca++ coming from ER, GA, mitochondria
of platelets
 Retraction pulls edges of broken blood vessels
 contributes further to state of hemostasis
D. Blood Coagulation Sequential Pathways
Intrinsic pathway - everything necessary for it to occur
is in the blood
Extrinsic pathway - a cellular element outside the blood
is needed. See Appendix B for the two clotting pathways.
 Clotting occurs by both pathways simultaneously
when a blood vessel ruptures
 Tissue factor - initiates extrinsic pathway
 Contact of Factor XII and platelets with vascular wall
collagen - initiates intrinsic pathway
DIFFERENCE BETWEEN THE TWO :
 Extrinsic factor is explosive and can occur in as little
as 15sec
 Intrinsic pathway is slower requiring 1 to 6 minutes
The two pathways merge at factor Xa which catalyzes the
conversion of prothrombin to thrombin → formation of
fibrin.
ROLE OF CALCIUM
 Is required by both extrinsic and intrinsic pathways
 Blood clotting can be prevented outside of the body
by reducing calcium concentrations through :
o Deionizing calcium through reaction with citrate
o Precipitating calcium with substances like
oxalate
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 PHYSIOLOGY
LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS
DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA
Extrinsic Pathway
Fig. 7 Extrinsic pathway for initiating blood clotting
 Triggered by injury to vessels
 Also known as tissue factor pathway
 Tissue factors from exposed tissue and blood
vessels activates factor VII → activated to factor
VIIa
 Tissue factor-factor VIIa complex on plasma
membrane catalyzes activation of factor IX, which
catalyzes activation of factor X → conversion of
prothrombin to thrombin
 Usual way of initiating clotting in the body
 Thrombin initially generated only using this pathway
o too small to produce adequate, sustained
coagulation
o large enough to trigger thrombin’s positive
feedback effects on the intrinsic pathway
o all that is needed to trigger intrinsic pathway
independently of factor XII
 Provides means for recruiting the more potent
intrinsic pathway without participation of factor XII
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Intrinsic Pathway
Fig. 8 Intrinsic pathway for initiating blood clotting
 Initiates upon trauma to the blood or exposure
of the blood to collagen from a traumatized
blood vessel wall.
1. Blood trauma causes (1) activation of Factor XII
and (2) release of platelet phospholipids.
 Factor XII → activated Factor XII or ”Factor
XIIa” (activated upon contact with collagen/
wettable surface like a glass)
 Simultaneously, lipoprotein platelet factor 3
from platelet phospholipids is released.
2. Activation of Factor XI by Factor XII
 Reaction requires high-molecular-weight
kininogen and accelerated by prekallikrein.
3. Activation of Factor IX by Factor XI
4. Activation of Factor X
 Activated by Factor IXa, VIIIa, with platelet
phospholipids and Factor III from traumatized
platelets.
 ↓supply Factor VIII or ↓platelets = ↓activation
of Factor X
o Absent clotting factor: Factor VIII =
classic hemophilia
o Hence, Factor VIII as “antihemophilic
factor”
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 PHYSIOLOGY
LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS
DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA
o Absent clotting factor: platelets
thrombocytopenia
5. Formation of prothrombin activator
 Same as the last step in extrinsic pathway
 Formation of the prothrombin activator
complex (Factor Xa + Factor V + platelet or
tissue phospholipids)
 Initiates the cleavage of prothrombin →
thrombin
E. Intravascular Anticoagulants
Endothelial Surface Factors
1. Smoothness of the endothelial surface →
prevents contact activation of intrinsic clotting
system.
2. Glycocalyx layer on the endothelium → repels
clotting factors & platelets
3. Protein Thrombomodulin on endothelium →
binds to thrombin (thrombomodulin – thrombin
complex)
o Complex activates plasma protein
Protein C that inactivates Factor Va &
VIIIa.
Fibrin & Antithrombin III
 Anticoagulants that remove thrombin from the blood.
 Fibrin fibers
o Adsorbs 85-90% of thrombin during clot
formation → prevents the spread of thrombin →
prevents excessive spread of clot.
 Antithrombin III
o Combines with unadsorbed thrombins →
inactivation of thrombin for 12-20 mins.
Heparin
 Used widely as pharmacological agent in medical
practice in much higher concentrations to prevent
intravascular clotting.
 Has little or no anticoagulant property BUT when
combined with Antithrombin III, effectiveness of the
latter increases by 100-1000x.
 Hence, removal of free thrombin is almost
instantaneous.
 Heparin – antithrombin complex removes
coagulation Factors XIIa, XIa, Xa, and IXa →
increased anticoagulation.
 Diffuses into the circulatory system from secretions
(in small amounts) mainly by basophilic mast cells
located at the precapillary CT throughout the body.
 Similarly, basophils release heparin in the plasma.
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=  Mast cells are abundant in the capillaries of the
lungs and liver where many embolic clots are formed
in slowly flowing venous blood hence preventing
further clot growth.
F. Lysis of Blood clots caused by Plasmin
 Plasminogen/ profibrinolysin
o Euglobin in plasma proteins that becomes
plasmin/ fibrinolysin when activated.
 Plasmin
o Proteolytic enzyme that digests fibrin fibers and
protein coagulants fibrinogen, Factor V, Factor
VIII, prothrombin, and Factor XII. Thus,
causing lysis of a clot and sometimes
hypocoagulability of the blood.
 Large amount of plasminogen (which will not cause
lysis, yet) is trapped in the clot.
 Injured tissues & vascular endothelium very slowly
release a powerful activator called tissue
plasminogen activator (t-PA)
 After a few days, when the clot has stopped the
bleeding, t-PA converts plasminogen to plasmin (this
one will finally cause lysis of the remaining
unnecessary blood clot)
 This plasmin system also reopens clot- blocked
small blood vessels thereby preventing occlusion of
millions of tiny peripheral vessels.
III. Conditions that cause excessive bleeding in
humans
 Excessive bleeding can result from a deficiency of
any one of the many blood-clotting factors.
A. Decreased Prothrombin, Factor VII, Factor IX,
And Factor X Caused By Vitamin K Deficiency
 Vitamin K is an essential factor to a liver carboxylase
that adds a carboxyl group to glutamic acid residues
on five of the important clotting factors: prothrombin,
Factor VII, Factor IX, Factor X, and protein C.
 Continually synthesized in the intestinal tract by
bacteria, so vitamin K deficiency seldom occurs in
healthy persons as a result of the absence of vitamin
K from the diet (except in neonates before they
establish their intestinal bacterial flora).
 Normal pathway
o Upon adding the carboxyl group to glutamic
acid residues on the immature clotting factors,
vitamin K is oxidized and becomes inactive.
o Another enzyme, vitamin K epoxide reductase
complex 1 (VKOR c1), reduces vitamin K back
to its active form.
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 PHYSIOLOGY
LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS
DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA
 2 main causes of Vitamin K deficiency:
a. Gastrointestinal disease
o vitamin K deficiency often occurs as a result
of poor absorption of fats from the
gastrointestinal tract because vitamin K is
fat soluble and is ordinarily absorbed into
the blood along with the fats.
b. Failure of the liver to secrete bile into the
gastrointestinal tract
o One of the most prevalent causes of
vitamin K deficiency
o Occurs either as a result of obstruction of
the bile ducts or as a result of liver disease
o Lack of bile prevents adequate fat
digestion and absorption and, therefore,
depresses vitamin K absorption as well.
Thus, liver disease often causes
decreased production of prothrombin and
some other clotting factors both because of
poor vitamin K absorption and because of
the diseased liver cells.
 In the absence of active vitamin K, subsequent
insufficiency of these coagulation factors in the
blood can lead to serious bleeding tendencies.
o In case of an operation: Vitamin K is injected
into surgical patients with liver disease or with
obstructed bile ducts before the surgical
procedure is performed. Ordinarily, if vitamin K is
given to a deficient patient 4 to 8 hours before
the operation and the liver parenchymal cells are
at least one-half normal in function, sufficient
clotting factors will be produced to prevent
excessive bleeding during the operation.
B. Hemophilia
 Occurs almost exclusively in males.
 Bleeding is usually from larger vessels
 2 types:
o Hemophilia A:
 Also called classic hemophilia
 it is caused by an abnormality or deficiency
of Factor VIII
 Factor VIII has two active components, a
large component with a molecular weight
in the millions and a smaller component
with a molecular weight of about 230,000.
The smaller component is most
important in the intrinsic pathway for
clotting, and it is deficiency of this part of
Factor VIII that causes classic hemophilia.
 Another bleeding disease with somewhat
different characteristics, called von
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Willebrand disease, results from loss of
the large component.
o Hemophilia B:
 Also called Christmas disease
 the bleeding tendency is caused by
deficiency of Factor IX.
 Both of these factors are transmitted genetically by
way of the female chromosome. Therefore, a woman
will almost never have hemophilia because at least
one of her two X chromosomes will have the
appropriate genes. If one of her X chromosomes is
deficient, she will be a hemophilia carrier,
transmitting the disease to half of her male offspring
and transmitting the carrier state to half of her
female offspring.
 Bleeding trait:
o Hemophilia can have various degrees of
severity, depending on the genetic deficiency.
o Bleeding usually does not occur except after
trauma, but in some patients, the degree of
trauma required to cause severe and prolonged
bleeding may be so mild that it is hardly
noticeable.
 Intervention: When a person with classic
hemophilia experiences severe prolonged bleeding,
almost the only therapy that is truly effective is
injection of purified Factor VIII.
C. Thrombocytopenia
 Presence of very low numbers of platelets in the
circulating blood.
 Bleeding is usually from many small venules or
capillaries. As a result, small punctate hemorrhages
occur throughout all the body tissues. The skin of
such a person displays many small, purplish
blotches, giving the disease the name
thrombocytopenic purpura.
 Normal count of platelets: 150,000 to 300,000/µl
 Ordinarily, bleeding will not occur until the number
of platelets in the blood falls below 50,000/µl
(Levels as low as 10,000/µl are frequently lethal).
 Even without making specific platelet counts in the
blood, sometimes one can suspect the existence of
thrombocytopenia if the person’s blood clot fails to
retract. As pointed out earlier, clot retraction is
normally dependent on release of multiple
coagulation factors from the large numbers of
platelets entrapped in the fibrin mesh of the clot.
 Most common: idiopathic thrombocytopenia, which
means thrombocytopenia of unknown cause. For
unknown reasons, specific antibodies have formed
and react against the platelets to destroy them.
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 PHYSIOLOGY
LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS
DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA
 Interventions:
o Relief from bleeding for 1 to 4 days by giving
fresh whole blood transfusions that contain large
numbers of platelets.
o Also, splenectomy is often helpful, sometimes
effecting almost complete cure because the
spleen normally removes large numbers of
platelets from the blood.
IV. Thromboembolic Conditions
A. Thrombi & Emboli
 Thrombus – abnormal clot that develops in a blood
vessel
 Emboli – freely flowing clots; previously attached to
a blood vessel as a thrombus
o From large arteries/left side of the heart - will
flow peripherally & plug the arteries/arterioles in
the brain, kidneys, or elsewhere
o From venous system/right side of the heart –
will flow into the lungs to cause pulmonary
arterial embolism
B. Causes of Thromboembolic Conditions
Causes of Thromboembolic Conditions
1.) Roughened endothelial surface of a blood vessel –
cause by arteriosclerosis, infection, or trauma
2.) Sluggish blood flow
C. Use of t-PA (Tissue Plasminogen Activator)
For Treating Intravascular Clots
 delivered to a thrombus via a catheter
 activates plasminogen to plasmin which dissolves
some intravascular clots
D. Conditions
Femoral Venous Thrombosis
 happens due to immobility of patients confined to
bed & propping of the knees with pillows
 causes blood stasis in one or more of the leg veins
 clot grows in the direction of the slowly moving
venous blood (entire length of the leg veins/up to the
common iliac vein & inferior vena cava
 1 out of 10 times the clot disengages and may lead
to massive pulmonary embolism
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Massive Pulmonary Embolism
 massive blockage of the pulmonary arteries
Disseminated Intravascular Coagulation
 results from the presence of large amounts of
traumatized/dying tissue that releases great
quantities of tissue factor into the blood plugging
small peripheral blood vessels
 occurs in patients with widespread septicemia –
where circulating bacteria/bacterial toxins
(endotoxins) activate clotting mechanisms
 diminishes delivery of oxygen & other nutrients to
the tissues that leads to circulatory shock
(septicemic shock)
 peculiar effect: patient on occasion begins to bleed –
due to clotting factors being removed by the
widespread clotting, few procoagulants remain for
hemostasis
V. Anticoagulants for Clinical Use
A. Heparin
 Intravenous
 extracted from animal tissues & prepared in almost
pure form
 injection of 0.5 to 1mg/kg of body weight cause
blood clotting time to increase from a normal of
about 6 mins. to 30 or more mins.
 immediately prevents or slows down
thromboembolic condition
 lasts about 1.5 to 4 hours
 destroyed by the enzyme heparinase
B. Coumarin
 ex. Warfarin
 causes the amount of active prothrombin and
Factors VII, IX, and X to fall by inhibiting the enzyme
VKOR c1 – which converts inactive oxidized form of
vit. K to its active, reduced form
 coagulation process is not blocked immediately
 coagulant activity decreases to about 50% of normal
by the end of 12 hrs and to about 20% of normal by
the end of 24 hrs
 normal coagulation returns 1 to 3 days after
discontinuing coumarin therapy
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 PHYSIOLOGY
LE# 2 LECTURE #2.05 BLOOD PHYSIOLOGY II: HEMOSTASIS
DATE OF LECTURE: July 16. 2019
INSTRUCTOR: Dr. Geraldine Susan Caceres-Tengco, MBA

C. Prevention of Blood Coagulation Outside the Body  Normal Value: 12 seconds

 Siliconized containers
o prevents clotting of collected blood for 1 hour or
more
o silicone prevents contact activation of platelets
& Factor XII
 Heparin
o used in surgical procedures in which the blood
must be passed through a heart-lung machine or
artificial kidney machine and then back into the
person
 Soluble oxalate compound (substances that
decrease the concentration of calcium ions)
o causes precipitation of calcium oxalate from the
plasma thereby decreasing the ionic calcium
level so much, hence, blocking blood coagulation
o can be toxic to the body
 Negatively charged citrate ion – sodium, ammonium,
or potassium citrate (substances that deionizes the
blood calcium)
o citrate ion combines with calcium ions in the Fig. 9 Relation of prothrombin concentration in the blood
blood to cause an un-ionized calcium compound to prothrombin time
– lack of ionic calcium prevents coagulation
o removed from the blood within a few minutes by  International Normalized Ratio (INR) – standardizes
the liver and is polymerized into glucose or the measurement of prothrombin time.
metabolized directly for energy
o 500ml of citrated blood can be transfused into  International sensitivity index (ISI) indicates the
recipient within a few minutes without activity of the tissue factor with a standardized
consequences sample. The ISI usually varies between 1.0 and 2.0.
o however, if liver is damaged/if large quantities are
given too rapidly, citrate ions may not be
removed quickly enough which can greatly
depress the level of calcium ion, which can result o Normal range for INR: 0.9 to 1.3
in tetany & convulsive death o High INR: 4 or 5 (high risk of bleeding)
o Low INR: <0.9 (chance of having a clot)
VI. Blood Coagulation Tests o Patients under Warfarin therapy: 2.0 to 3.0

1. Bleeding Time – time for skin wound to stop

bleeding;
done to assess platelet function Recommendation for fun learning read Cells at Work:
 Normal Value: <6 mins https://mangarock.com/manga/mrs-serie-99034
or watch it 
2. Clotting Time – time required for blood to form a clot;
Used to diagnose hemophilia
 Normal Value: 6 to 10 mins REFERENCES

3. Prothrombin Time and International Normalized  PPT & Lecture

Ratio  Guyton & Hall 13th edition
Prothrombin Time – time required for
coagulation to take place; prothrombin
concentration determines the shortness of time

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