• BLOOD GROUPS.

• HEMOSTASIS AND BLOOD

COAGULATION
 PLAN of LECTURE
1. The modern idea about the blood group systems.
1.1. Agglutinogens and agglutinins.
1.2. The ABO blood group system.
1.3. The Rhesus blood group system.
1.4. The leucocytal blood groups. HLA system and its importance for medicine.
2. Physiological basis of the blood transfusion.
2.1. Definitions: “donor”, “recipient”.
2.2. The main rules of the donor blood matching.
3. The concept about hemostatic system.
4. The stages of the hemostatic process.
4.1. The 1st stage - vascular- platelet hemostasis.
4.2. The 2nd stage - coagulation hemostasis.
4.2.1. The classical theory of blood clotting (A.Shmidt).
4.2.2. The modern theory.
4.2.3. The phases of red blood clot formation.
4.2.3.1. Coagulation factors involved in each phase.
4.2.3.2. Intrinsic and extrinsic clotting system.
4.3. The 3rd stage – the clot retraction.
4.4. The 4th stage - fibrinolysis.
4.4.1. Fibrinolytic system.
5. Regulation of blood coagulation.
6. Anticlotting mechanisms.
6.1. Primary and secondary anticoagulants.
6.2. Anticoagulants with the direct and indirect action.
When blood transfusions from one
person to another were first attempted,
the transfusions were successful only
in some instances. Often
complications of transfusions occurred
that occasionally led to death.
The bloods of different
people have different
antigenic and immune
properties.
There are antibodies in the
plasma and antigens on the
surfaces of the red cells.
Antibodies in the plasma of one
blood react with antigens on the
surfaces of the red cells of
another blood.
 For this reason, it is easy for
blood from a donor to be
mismatched with that of a
recipient.
A recipient is a person
that receives something A donor is someone who
gives a part of their
(the recipient of the body or some of their
blood). blood to be used by
doctors to help a person
who is ill.
Blood types – the immuno-genetic
properties of the blood.
 Two particular groups of antigens are more
likely than the others to cause blood transfusion
reactions. They are the O-A-B system
and the Rh (rhesus) system.
 O-A-B BLOOD GROUPS
A and B Antigens
Two antigens (type A and type B) occur on
the surfaces of the red blood cells in a large
proportion of the population.
The another name of these antigens –
agglutinogens because they often cause
blood cell agglutination.
 These agglutinogens are inherited.
People may have neither of them,
one, or both simultaneously on their
cells.
 HEMOLYSIS is the rupture or
destruction of red blood cells with
releasing hemoglobin into the plasma.
 There are
four O-A-B blood types
depending on the presence or
absence of the A and B
agglutinogens.
 ORIGIN of
agglutinins in the
plasma. The
agglutinins are
gamma globulins, as
are other antibodies.
They are produced by
the same cells that
produce antibodies to
any other antigens.
 Blood Agglutinogens Agglutinins
type in erythrocytes in plasma

I(0) или 0 (I) - , 

II(А) или А (II) А 

III(В) или B (III) В 

IV(АВ) или АВ0 (IV) А, В -

Blood Typing
Before giving a transfusion, it is necessary
to determine the types of the recipient and
the donor blood so that the bloods can be
appropriately matched.
This is called blood
typing. Way:
1. One blood portion
is mixed with α and
another portion with β
agglutinin.
2. After 5 minutes the
mixture is observed.
 If the red blood cells
have become clumped or
agglutinated an
antibody-antigen
reaction has resulted.
 Universal donor The scheme of
the compatibility
of blood types

Universal recipient
Rh BLOOD TYPES
Along with the O-A-B blood
group system, the Rh system is
important in the transfusion of
blood.
Rhesus monkey (also rhesus
macaque) a small brown
macaque with red skin on the
face and rump, native to
southern Asia. It is often kept
in captivity and is widely used
in medical research.
 The major difference between the
O-A-B system and the Rh system:
in the O-A-B system, the
agglutinins develop spontaneously,
whereas in the Rh system,
spontaneous agglutinins almost
never occur.
The person must first be massively
exposed to an Rh antigen (by
transfusion of blood or by a
mother's having a baby who has the
antigen) before enough agglutinins
to cause a significant transfusion
reaction will develop.
Rh-Positive and Rh-Negative
People. There are six common
types of Rh antigens, each of
which is called an Rh factor.
These types are designated C,
D, E, c, d, and e.
A person who has the C antigen does not have
the c antigen, but the person missing the C
antigen always has the c antigen. The same is
true for the D-d and E-e antigens.
 The type D antigen is
widely prevalent in the
population and
considerably more
antigenic than the other
Rh antigens.

A person who has A person who does not

type D antigen is Rh have type D antigen is
positive. Rh negative.
 About 85% of all white
people are Rh positive and
15%, Rh negative. In
American blacks, the
percentage of Rh positives is
about 95, whereas in African
blacks, it is virtually 100%.
CHARACTERISTICS of Rh
transfusion reactions.
If an Rh-negative person has never
before been exposed to Rh-positive
blood, transfusion of Rh-positive
blood into that person causes no
immediate reaction.
 On subsequent transfusion of Rh-positive
blood into the same person, who is now
immunized against the Rh factor, the
transfusion reaction is greatly enhanced and
can be as severe as the transfusion reactions
caused by type A or B blood.
The HLA Complex of Antigens
HLA Human Leucocyte
Anyigen
 The most important antigens for
causing graft rejection are the HLA
antigens. Only six of these antigens
are present on the cell surfaces of
any one person, but there are about
150 different types to choose from.
 Hemolytic Disease of the Newborn
Erythroblastosis fetalis is a disease of the fetus and
neonate characterized by agglutination and
phagocytosis of the red blood cells.
The reason – the mother is Rh negative and the father is
Rh positive. The baby has inherited the Rh-positive
antigen from the father, and the mother has developed
anti-Rh agglutinins from exposure to the baby's Rh
antigen. In turn, the mother's agglutinins diffuse through
the placenta into the fetus to cause red blood cell
agglutination.
An Rh-negative mother having her first Rh-positive
child usually does not develop sufficient anti-Rh
agglutinins to cause any harm. About 3 per cent of
second Rh-positive babies exhibit some signs of
erythroblastosis fetalis. About 10 per cent of the
third babies exhibit the disease. Conclusion – the
incidence rises progressively with subsequent
pregnancies.
 EFFECT OF THE
MOTHER'S
ANTIBODIES ON THE
FETUS.
They diffuse slowly
through the placental
membrane into the fetus's
blood and cause
agglutination of the fetus's
blood, their hemolysis and
releasing of hemoglobin
into the plasma.
HEMOSTASIS AND BLOOD
COAGULATION
Hemostasis is a prevention
of blood loss when a vessel
is severed or ruptured.
THE STAGES OF HEMOSTASIS:
1) primary or microcirculatory or vascular-
thrombocytary (1-3 min)
(result – formation of a platelet plug or
white thrombus);
2) secondary – coagulation (5-10 min)
(result – formation of a blood clot or red
thrombus);
3) retraction (30 min - 3 h)
(result – contraction of a blood clot);
4) fibrinolysis (several days)
(result – split of a blood clot).
THE STAGES OF HEMOSTASIS
I. III.

Primary
(white Retraction
thrombus)
II. IV.
Secondary
(red Fibrinolysis
thrombus)
 Platelet Plug or Blood Clot
If the rent in the blood vessel is very small it
is sealed by a platelet plug, rather than by a
blood clot.
 Vascular Constriction
Immediately after a blood vessel is cut or ruptured,
the smooth muscular cells of the vessel wall
contract. Mechanisms:
1) nervous reflexes – are initiated by pain or other
impulses that originate from the traumatized vessel
or from nearby tissues;
2) local myogenic spasm – is initiated by direct
damage to the vascular wall;
3) local humoral factors from the traumatized
tissues and blood platelets – the platelets release the
vasoconstrictor substance thromboxane A2.
 The value of vascular
spasm is the decrease of the
flow of blood from the
vessel rupture and the loss
of blood.
 Mechanism of the Platelet Plug
When platelets come in contact with a
damaged vascular surface, they
adhere to the exposed collagen and
von Willebrand factor in the wall via
the receptors on their membrane.
After that they immediately change
their characteristics drastically.
1.They begin to swell.
2. They assume irregular forms with numerous
irradiating pseudopods protruding from their surfaces.
3. Their contractile proteins contract and cause the
release of granules that contain multiple active factors.
4. They become sticky and stick to the collagen fibers.
5. Their enzymes form thromboxane A2, which is
secreted into the blood → Vascular Constriction.
6. They also secrete large quantities of ADP (release it
from their granules). ADP acts on the ADP receptors
in the platelet membranes to produce further
accumulation of more platelets (platelet aggregation).
 General Mechanism
All research workers in the field of blood coagulation
agree that clotting takes place in three essential steps: (1) In
response to rupture of the vessel or damage to the blood itself, a
complex cascade of chemical reactions occurs in the blood
involving more than a dozen blood coagulation factors. The net
result is formation of a complex of activated substances
collectively called prothrombin activator. (2) The prothrombin
activator catalyzes the conversion of prothrombin into thrombin.
(3) The thrombin acts as an enzyme to convert fibrinogen into
fibrin fibers that enmesh platelets, blood cells, and plasma to
form the clot.
 Conversion of Prothrombin to Thrombin
After prothrombin activator has been formed as a result of
rupture of the blood vessel or as a result of damage to special activator
substances in the blood, the prothrombin activator then, in the
presence of sufficient amounts of ionic Ca++, causes conversion of
prothrombin to thrombin. The thrombin in turn causes polymerization
of fibrin­ogen molecules into fibrin fibers within another 10 to 15
seconds. Thus, the rate-limiting factor in causing blood coagulation is
usually the formation of prothrombin activator and not the subsequent
reactions beyond that point because these terminal steps normally
occur rapidly to form the clot itself.
Platelets also play an important role in the conversion of
prothrombin to thrombin because much of the prothrombin first
attaches to prothrombin receptors on the platelets that have already
bound to the damaged tissue. Then this binding accelerates the
formation of thrombin from the prothrombin, occurring exactly in the
tissue where the clot is needed.
 Extrinsic Mechanism for Initiating Clotting
The extrinsic mechanism for initiating the formation of
prothrombin activator begins with a traumatized vascular wall or
extravascular tissues and occurs according to the following steps.
1. Release of tissue factor. Traumatized tissue releases a
complex of several factors called tissue factor or tissue
thromboplastin. This is composed especially of phospholipids
from the membranes of the tissues and a lipoprotein complex
containing an important proteolytic enzyme.
2. Activation of Factor X—role of Factor VII and tissue
factor. The lipoprotein complex of tissue factor further
complexes with blood coagulation Factor VII and, in the
presence of calcium ions, acts enzymatically on Factor X to form
activated Factor X.
 3. Effect of activated Factor X to form prothrombin
activator—role of Factor V. The activated Factor X combines
immediately with tissue phospholipids that are part of tissue factor or
with additional phospholipids released from platelets as well as with
Factor V to form the complex called prothrombin activator. Within a
few seconds, this splits prothrombin to form thrombin, and the
clotting process proceeds as already explained. At first, the Factor V
in the prothrombin activator complex is inactive, but once clotting
begins and thrombin begins to form, the proteolytic action of
thrombin activates Factor V. This then becomes an additional strong
accelerator of prothrombin activation. Thus, in the final prothrombin
activator complex, activated Factor X is the actual protease that
causes splitting of prothrombin to thrombin, activated Factor V
greatly accelerates this protease activity, and phospholipids act as a
vehicle that further accelerates the process. Note especially the
positive feedback effect of thrombin, acting through Factor V, in
accelerating the entire process once it begins.
 Intrinsic Mechanism for Initiating Clotting
The second mechanism for initiating the formation of prothrombin
activator, and therefore for initiating clotting, begins with trauma to the blood
itself or exposure of the blood to collagen in a traumatized blood vessel wall and
then continues through the following series of cascading reactions.
1. Blood trauma causes activation of Factor XII and release of platelet
phospholipids. Trauma to the blood or exposure of the blood to vascular wall
collagen alters two important clotting factors in the blood: Factor XII and the
platelets. When Factor XII is disturbed, such as by coming into contact with
collagen or with a wettable surface such as glass, it takes on a new configuration
that converts it into a proteolytic enzyme called "activated Factor XII."
Simultaneously, the blood trauma also damages the platelets because of adherence
to either collagen or a wettable surface (or by damage in other ways), and this
releases platelet phospholipid that contains the lipoprotein called platelet factor 3,
which also plays a role in subsequent clotting reactions.
 2. Activation of Factor XI. The activated Factor XII acts
enzymatically on Factor XI to activate this as well, which is the
second step in the intrinsic pathway. This reaction also requires
HMW (high-molecular-weight) kininogen and is accelerated by
prekallikrein.
3. Activation of Factor IX by activated Factor XI. The
activated Factor XI then acts enzymatically on Factor IX to activate
this factor also.
4. Activation of Factor X—role of Factor VIII. The activated
Factor IX, acting in concert with activated Factor VIII and with the
platelet phospholipids and factor 3 from the traumatized platelets,
activates Factor X. It is clear that when either Factor VIII or platelets
are in short supply, this step is deficient. Factor VIII is the factor that
is missing in the person who has classic hemophilia, for which
reason it is called antihemophilic factor. Platelets are the clotting
factor that is lacking in the bleeding disease called
thrombocytopenia.
 5. Action of activated Factor X to form prothrombin
activator—role of Factor V. This step in intrinsic pathway is
the same as the last step in the extrinsic pathway. That is,
activated Factor X combines with Factor V and platelet or
tissue phospholipids to form the complex called
prothrombin activator. The prothrombin activator in turn
initiates within seconds the cleavage of prothrombin to form
thrombin, thereby setting into motion the final clotting
process, as described earlier.