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Section 3

 Definition:
The process the body uses to
stop the flow of blood when the
vascular system is damaged.

Prevention of blood loss.

Mechanisms of Hemostasis:
 Vascular spasm
 Formation of a platelet plug
 Formation of a blood clot as a result of
blood coagulation
 Eventual growth of fibrous tissue into the
§1. Vascular Constriction

 The trauma to the vessel wall itself

causes the vessel to contract.
 Contraction causes:
1. Nervous reflexes
2. Local myogenic spasm (Most)
3. Local humoral factors from the
traumatized tissues and platelets
(Most for smaller vessels)
§2. Formation of a platelet
If the rent in the blood vessel
is very small, it is often sealed by
a platelet plug, rather than by a
blood clot.
Damaged vascular surface
(eg. Collagen fibers)

Swell Protrude Contractile Become Secrete Form

irradiating protein sticky AdenosineThromboxane
pseudopods contract diphosphate A2
Release granule Adhere to
containing Collagen and
active factors Von willebrand
(fibrin-stablizing factor,
factor (vWF)
growth factor, etc)
§3. Blood Coagulation in the
Ruptured Vessel
 In 15 to 20 seconds: clot begins to develop.
(if the trauma to the vascular wall has been severe)
Or in 1 to 2 minutes.
(if the trauma has been minor)
 Within 3 to 6 minutes: filled with clot.

 After 20 minutes to an hour: clot retract

§4. Fibrous Organization or
Dissolution of the Blood
 Two courses of blood clot:
 Invaded by fibroblasts.
 Dissolve.

 Fibroblasts invasion: within a few

 Organization of the clot into fibrous
tissue: within 1 to 2 weeks.
Blood Coagulation
 Definition
 a process in which liquid blood is
changed into a semisolid mass (a
blood clot)
Coagulation Factors
Factor Name Plasma half-
life (h)

I Fibrinogen 纤维蛋 72 - 96
II Prothrombin 凝血 60
III Tissue Factor or -
thromboplastin 组织
IV Ca++ -
V Proaccelerin 前加 15
VII Proconvertin 前转变 5

Factor Name Plasma
half-life (h)

IX Antihemophilic B factor or 25
Christmas factor 血浆凝血激

X Stuart or Stuart-Prower 40
XI Plasma thomboplastin 45-65
antecedent 血浆凝血激酶前质子

XII Hageman factor, contact 60

factor 接触因子
XIII Fibrin stabilizing factor 纤维 150
Three essential steps of
 Formation of prothrombinase complex
(prothrombin activator)
 Prothrombin (FII) activated
 Formation of fibrin (Ia)
§1. Initiation of coagulation:
Formation of Prothrombin activator

Trauma to the Extrinsic pathway

vascular wall and
surrounding tissues; Prothrombin
Trauma to the blood activator
Intrinsic pathway

Prothrombin activator: factor Xa-Va

Intrinsic Pathway
 Intrinsic Pathway is defined as a
cascade that utilizes only factors
that are soluble in the plasma.
Contact with the collagen
under subendothelial cell
Extrinsic Pathway

 Extrinsic Pathway triggered by

tissue damage, which cause the
release of factor III ( Tissue
Factor )
Contact with the collagen
under subendothelial cell
§2. Conversion of prothrombin to
(FII) (FIIa)
 The rate-limiting factor in causing blood
coagulation is the formation of prothrombin
 Platelets’ role in FII→FIIa.
Platelets adhere to the damaged tissue, and
provide prothrombin receptors to bind with
This binding accelerate the conversion and
localize the formation of thrombin.
§3. Conversion of fibrinogen to fibrin ---
formation of the clot
 Action of thrombin on fibrinogen to form fibrin.
 Thrombin acts on fibrinogen to remove four
peptides from each molecule of fibrinogen,
forming a molecule of fibrin monomer. F
 Thrombin activate fibrin-stabilizing factor
( plasma globulins, platelets) which promote the
formation of Cross-linked fibers. F
Formation of fibrin
Prothrombin (II)
Prothrombin activator Ca2+
Thrombin (IIa)

Fibrinogen (I) Fibrinogen monomer

Fibrin fibers
Thrombin activated

Cross-linked fibrin fibers

 The classical model of blood
coagulation involves a series
(or "cascade") of zymogen
activation reactions.

 Coagulation can be initiated

via the “intrinsic” or
“extrinsic” pathway.
 Both the intrinsic and the extrinsic pathways
proceed through a common pathway by
forming activated factor X (factor Xa-Va-Ca2+
Prothombin Activator)

 Amplification of coagulation reactions.

 The intrinsic and the extrinsic pathways are

highly interconnected.
Vicious circle of clot
(Amplification of coagulation)
 Most important cause: thrombin act
on many blood-clotting factors in
addition to fibrinogen.
 Prothrombin

 Other blood-clotting factors

responsible for the formation of
promthrombin activator, eg, VIII, IX,
X, XI and XII
 Aggregation of platelets.
 Amplification of
FIIa activate FXI.
 Intrinsic pathway
interconnect with
extrinsic pathway
TF-VIIa complex
activate FIX.
Factors That Affect Coagulation

 Procoagulants
More than 50 kinds in blood
 Anticoagulants
 Whether blood will coagulate depends on
the balance between Procoagulants and
 In the blood stream, the anticoagulants
normally predominate.
 The reasons that blood can flow
through vessels fluently are as
 There is no injury in blood vessel.
 Most of clotting factors are present
in blood with inactive state.
 Thereare some anticoagulants
(Compounds that do not allow
blood to clot) exist in blood.
Anticoagulative factors

1. Endothelial surface factors:

(1) the smoothness of the
endothelial surface
(2) a layer of glycocalyx on the
(3) thrombomodulin bound with
endothelial membrane, which
binds with thrombin.
Thrombomodulin - thrombin complex

Remove Protein C (anticoagulant)



activate inactivate
Anticoagulative factors
2. Antithrombin action of fibrin and
antithrombin III.
Both work by removing thrombin.
(1) fibrin fibers adsorb thrombin
(2) antithrombin III (an alpha-globulin,
produced in liver and endothelial
cells) combine with unadsorbed
thrombin and then inactive it.
Anticoagulative factors
3. Heparin.
(1) It combines with antithrombin III,
then the effectiveness of antithrombin III
in removing thrombin increases by a
hundredfold to a thousandfold.
(2) The complex also removes Xa, XIa,
IXa and FXIIa.
Heparin forms a high-
affinity complex with
antithrombin (AT-H).

The formation of AT-

H complex greatly
increases the rate of
inhibition of two
principle procoagulant
proteases, factor Xa
and thrombin (FII).
Anticoagulative factors
3. Heparin.
(3) Mainly formed in basophilic mast
cells in the pericapillary connective
tissue and basophilic cells of the blood.
(4) Its concentration in the blood is
normally low.
(5) Widely used as a pharmacological
agent in medical practice.
Anticoagulative factors
Coumarins Competitive inhibitors of
vitamin K in the
1,3-indanedions biosynthesis
  of prothrombin
5. Tissue factor pathway inhibitor
(TFPI, lipoprotein-associated
coagulation inhibitor )
 TFPI in vivo is thought to be
synthesized mainly by endothelial
 TFPI inhibits the activation of the
extrinsic coagulation cascade through
its ability to inhibit factor Xa and
combine with FVIIa-TF complex.
VII Ca2+
TF Complex of inhibitor
TF —Xa
IX IXa (1)


Catalysis Convert
Clot retraction---serum
 Definition
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.
 Difference from plasma: Serum have no
fibrinogen and most of other clotting factors.
Breakdown of Blood Clots
 Fibrinolysis
 Fibrinolysis leads to the breakdown of
fibrin clots (blood clots) and is caused by
the action of several enzymes

 Whenever fibrinolysin (plasmin) is formed

in a blood clot, it can cause lysis of clot
and also destruction of many clotting
factors, thereby causing
hypocoagulability of the blood.
Lysis of blood clots--
 Plasminogen (profibrinolysin) mainly
formed in liver
 Plasminogen can lose one peptide and
then convert into plasmin.
 Plasmin (fibrinolysin) can digest fibrin
fibers, fibrinogen, FV, FVIII, prothrombin
and FXII.
Activation of Plasminogen to
Form Plasmin
 Activators:
Tissue plasminogen activator (t-PA),
Urine plasminogen activator (u-PA)
 Inhibitors:
Plasminogen activator inhibitor type-1
α 2-antiplasmin
Kallikrein FXIIa

tPA uPA Urokinase

(Endotheli (kidney)
Plasminogen m) Plasmin
α 2-antiplasmin (liver)
Fibrin (or fibrinogen) degradation

Catalysis; Convert; Inhibit.

In normal situation, fibrinolysis
retains at a certain degree and
area to keep the balance of
Coagulation and Fibrinolysis.
 In normal situation, PAI-I is about 10-fold
amount of t-PA. So the blood keeps in a
hypo-fibrinolysis state.
 When fibrin forms, endothelium secrete
more t-PA, and fibrin has a higher
affinity with t-PA and plasminogen.
 t-PA – fibrin – plasminogen escape the
PAI-I inactivation effect on t-PA and help
t-PA to activate plasminogen.
 Plasmin can bind with fibrin to escape
α 2-antiplasmin inactivation effect.
Functions of plasmin

To remove minute clots

from millions of tiny
peripheral vessels to avoid
Section 4

Blood Groups
Antigenicity causes immune
reactions of blood

 When blood transfusion were

first attempted, the transfusions
were successful only in some
 Failure: agglutination and
 The clumping together of red
cells in blood as a result of
antibodies attaching to
antigens on the surface of the
 Proteins that provide the specific signature
or identity to blood or other tissue cells. 
 When alien antigens are introduced into the
body, they stimulate the production and
mobilization of antibodies. 
 Antigens are found on the surface of blood
and other tissue cells as well as bacteria
and viruses.
 In blood transfusion failure, the most
important antigen is some proteins on the
donor’s red cell membrane.
 Proteins produced by the body to identify and
neutralize or destroy alien antigens. 
 Antibodies are involved in the rejection of
mismatched blood transfusions and organ
 They are also responsible for recognizing and
eliminating bacteria and viruses. 
 Antibodies provide a major defense for our bodies
against invasion by alien organisms.
 In blood transfusion failure, the most important
antibody is some proteins in the recipient’s
Multiplicity of antigens in the blood
 At least 30 commonly
occurring antigens and
hundreds of other rare
antigens have been found in
human blood.
 The most important:

ABO system and Rh

Discoverer of ABO system
 Karl Landsteiner
discovered ABO
blood type in 1900
and 1901.
 In 1930, he
received the Nobel
Prize for this

Karl Landsteiner
ABO blood
 There are four types: A, B, AB, and O
decided by the antigens (Antigen A/B)
on RBC membrane.

 There are two antigens and two

antibodies that are mostly responsible
for the ABO types.
Antigen and Antibody in ABO Blood Type

ABO Antigen Antigen Antibody Antibody

Blood  A   
Type B  anti-A anti-B

A yes no no yes

B no yes yes no

O no no yes yes

AB yes yes no no  

Genetic Inheritance Patterns
 ABO blood types are inherited through
genes on chromosome 9
 Do not change as a result of
environmental influences during life.
 An individual's ABO type is determined
by the inheritance of 1 of 3 alleles (A, B,
or O) from each parent.
alleles: alternate forms or varieties of a
gene which is responsible for hereditary
characteristics. . 
Genotype AA AO BB BO AB OO
Phenotype A A B B AB O

 There must be two alleles of A, B and O to

form a person’s Genotype in blood type.
 Both A and B alleles are dominant over O.
Parent Alleles A B O

(A) (AB) (A)
(AB) (B) (B)
(A) (B) (O)

The possible ABO alleles for one parent are in the top
row and the alleles of the other are in the left
column. Offspring genotypes are shown in white.
Phenotypes are red.
Titer of the agglutinins at
different ages.
 Immediately after birth, antibody
anti-A and anti-B in plasma are
almost zero.
 2 to 8 months, infants begin to
produce the certain antibody.
 A maximum titer is usually at 8 to 10
years of age.
 The antibody (agglutinins) are IgM
(most, spontaneous developed
antibody) and IgG (little, immune
antibody) immunoglobulin

 Small amounts of group A and B

antigens enter the body in food, in
bacteria, and in other ways.
Unagglutinated blood smear Agglutinated blood

Sometimes when the blood of two

people is mixed together, it clumps or
forms visible islands in the liquid
plasma--the red cells become
attached to one another.  
This is agglutination.
Antibodies seeking Antibodies agglutinating
specific antigens red cells
Agglutination process in
transfusion reactions

 IgG (2 binding sites) and IgM (10 binding sites) bind

with antigen on RBC membrane.
 RBC bound together and clump.
 RBC clumps plug small blood vesssels.
 Agglutinated cells destroyed (physical distortion or
attack by phagocytic white cells) and releasing
hemoglobin (hemolysis).
Acute Hemolysis Occurs in
some Transfusion
 Antibodies activate the complement
system, which releases proteolytic
enzymes that rupture the cell
 Acute hemolysis is far less common
than delayed hemolysis which follows
Anti B Anti A Anti-A-B (Serum)

ABO Blood Typing



Differences between ABO system and
Rh system
Contact Agglutinins Must be massively
history develop exposed to
spontaneously. antigens.

Antigen A, B C, c, D, d, E, e
Blood A, B, O, AB Positive (have D)
type Negative (have no
Antibody IgM (most, can IgG (can go
not go through through placenta)
Rh immune response
 Formation of Anti-Rh Agglutinins.
After being exposed to antigen, anti-Rh
agglutinins develop slowly, 2 to 4 months
to get the maximum concentration of
 If an Rh-negative person (never exposed to
Rh-positive blood) take transfusion of Rh-
positive blood, he will have a delayed mild
transfusion reaction.
 Repeatedly exposition can make
transfusion reaction very severe.
Hemolytic disease of the
 In the case that Mother is Rh-
negative and baby is Rh-positive.
 An Rh-negative mother having her
first Rh-positive child usually does
not develop sufficient anti-Rh
agglutinins to cause any harm.
The rule of Blood
 Blood typing. Avoid mismatch.
 ABO type match and Rh type match
(especially in procreation-age woman and
patients needing repeated transfusions).
 Cross-match test
1. Main test: Donor’s RBC + Recipient’s serum
2. Subordination test: Donor’s serum + Recipient’s RBC
 Advances: transfusion of blood components