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PHYSIOLOGY OF HEMOSTASIS SYSTEM
Pulatova Shakhnoza Khaydarovna
Head of the Department of Anesthesiology and Reanimation
Bukhara Medical Institute
Barnoyev Saidjon Sharifovich
Master of the Department of Pediatric Anesthesiology and Resuscitation,
Bukhara Medical Institute
https://doi.org/10.5281/zenodo.11112224
The hemostasis system is a complex, labile and multicomponent system
that includes mechanisms that are necessary to achieve a certain result. One of
these complex mechanisms is to stop bleeding from an injured vessel. , one of
the second most important mechanisms is the mechanism that prevents the
spread of this process to areas outside the damaged area. are considered to have
inhibitors [44].
The main systems that provide hemostasis include the blood-vascular
platelet system, the coagulation or plasma hemostasis system, and the protease
and fibrinolysis systems that limit their high activity. can participate in
functional mechanisms that contradict each other. The simultaneous
participation of such a component in several processes causes physiological
hemostasis to have the following characteristics:
- high activity of the system of hemostasis, that is, due to the positive
functioning of the coagulation network, the activation of the feedback
mechanism in relation to it leads to the repeated activation of this process.
- locality of the hemostasis system, i.e. non-spreading of the thrombus
formation process in the area outside the damaged vessel due to the effect of the
anticoagulation system.
- the fact that the activation of the hemostasis system is of a temporary
nature, that is, the thrombus formed in the damaged vessel meets recanalization
over time [45].
The primary reaction of the div to a vessel injury is the spasm of the
vessel. Vasoconstriction slows down the blood flow in the injured area and, as a
result, reduces the level of blood loss. At the same time as the blood circulation
slows down, there is a local effect of the factors of the hemostasis system
activated in the injured area. Blood in the injured area - spasm of blood vessels
first occurs on the basis of a neuro-reflex mechanism, then it occurs under the
influence of chemical mediators released from activated thrombocytes, that is,
serotonin and thromboxane A2. The process of interaction of platelets with the
damaged subendothelial structures of blood vessels occurs primarily through
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adhesion to the damaged area with collagen. Adhesion of platelets occurs under
the influence of Willebrand factor dissolved in blood plasma, and this factor It is
activated when platelets come into contact with the damaged vascular
subendothelium. As a result of the adhesion of platelets, their activation occurs.
One of the signs of their activation is the release of secretory factors in the form
of granules from platelets, that is, thromboxane A2, ADF and factors that
stimulate platelet aggregation. Modern tests show that activated platelets
secrete plasma hemostasis factors: factor VIII, Willebrand factor, fibronectin,
beta-thromboglobulin and other platelet activators, and have a real
anticoagulant effect that reverses this process. secreted platelet factor IV is also
released. In addition, as a result of the activation of platelets, GPIIb-IIIa
receptors are formed on their surface, and fibrinogen in the plasma binds to
these receptors. The process of blood coagulation under the influence of plasma
factors is based on the limited proteolysis of protein molecules of coagulation
factors on the basis of a complex mechanism, and as a result, their active form is
formed. The naming of blood coagulation factors with Roman numerals is
accepted, and they are numbered from I to XIII. The active form of these factors
the numbers are prefixed with the letter "a". The important aspect of blood
clotting factors is that they are inactive or weakly activated in solution, and
when they come into contact with the negatively charged phospholipid
membrane, their activation occurs. As a result of the collision of platelets with
the collagen in the damaged vessel wall, they are connected to them and a direct
contact with the cell membrane is established. its activity is that it provides the
connection of enzyme complexes, enzymes and their cofactors and substrates.
Examples of such complexes are tenases (IXa+VIIIa-bCa+2+PF3),
prothrombinases (Xa+Va+Ca+2+PF3) possible [46].
Such complexes are important for the formation of optimally
structured enzyme molecules and their active centers, and under the influence
of such active centers, the speed of the reaction is accelerated ten thousand
times. Calcium ions participate in the stabilization of proteins involved in blood
coagulation with a tertiary structure.
The most important and central link in the process of formation of a
coagulation network is the activation of factor X. There are two mechanisms of
activation of factor X. The first mechanism occurs as a result of the effect of
factor IXa on the phospholipid membrane with the help of calcium ions. In this
enzymatic process, factor VIIIa macromolecules act as a matrix and accelerate
the enzymatic reaction thousands of times. This mechanism of hemostasis
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associated with contact phase factors is called the "internal activation
mechanism". This process is factor XI, which is a proenzyme of contact phase
factors and serine proteases. factor XIII, high molecular kininogen, prekallikrein
and kallikrein also participate in this process. A complex consisting of XII, XI,
prekallikrein and high molecular kininogen is formed in the damaged vessel
wall. In this process, a high molecular kininogen cofactor is considered and is
important in the formation of the complex. The characteristic feature of the
contact phase factors is that they are simultaneously activated and affect each
other. As an example, it can be said that active under the influence of factor XII in
the form, kallikrein is formed from prekallikrein, and in turn, kallikrein
increases the maximum enzymatic activity of factor XII. As a result of the
mechanism of internal activation of hemostasis, the formation of activated factor
XI occurs in the plasma. Factor XI in the active state o in turn, together with
calcium ions, it leads to the activation of factor IX. Activated factor IX activates
factor X.
The second and main activation of the hemostasis system, that is, the
activation of factor X, occurs with the participation of tissue factor (TF) and
factor VIIa. A small amount of factor VIIa is constantly in the blood plasma, but it
is tissue factor (TF) and calcium if it collides together with ions, its enzymatic
activity increases several times. Tissue factor is considered an intermembrane
protein. It is not normally present in blood plasma and endothelial cells. There
are domains on the surface layer of this protein, which allow these proteins to
bind to factor VIIa in the active state. Another important mechanism of factors of
the hemostasis system is the activation of factors VII and Xa. In addition, the
activation of factor VII is carried out under the influence of thrombin IXa, XII,
and it is several times more important than the activated factor X. its inactive
form is considered to be formed from prothrombin. This enzymatic process
takes place with the participation of the "prothrombinase enzyme complex",
which contains active factors such as Xa+Va+Ca+2+PF3. In this process, calcium
ions ensure the binding of prothrombin to the phospholipid membrane. factor
Va ensures the interaction of prothrombin with the active form of Xa. The above-
mentioned "prothrombinase enzyme complex" accelerates the proteolysis
process of prothrombin 500 thousand times. (α-thrombin) is formed. In the
functional implementation of the coagulation network, it is important that the
formation of thrombin affects and stimulates factors V, VII, XI involved in the
formation of thrombin and thrombocytes through a positive feedback effect. In
blood plasma after the formation of active thrombin, it affects fibrinogen in the
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blood plasma and causes its molecule to be enzymatically split. After such
molecular splitting, fibrinopeptides A and B are formed from Aa and Bp chains of
fibrinogen. This is a feature of polymerization in the side chain of
fibrinopeptides. after such polymerization, initial fibrin is formed in the
formation of a fibrin net. A strong peptide bond is formed between the fibrin
molecules formed by this enzyme, i.e. fibrin monomers standing next to each
other. As a result, a fibrin mesh covering the damaged area is formed in the
damaged vessel and blood clotting occurs.
The process of limiting blood coagulation in a damaged blood vessel is the
function of the anticoagulation system, which has anticoagulation properties.
This system includes factors that prevent the activation of groups of factors
involved in blood coagulation. It takes place in the intact endothelium located
adjacent to the damaged area of the vessel and leads to the formation of a
thrombus only in the damaged area. Such mechanisms include: annexin V -
competitive inhibition of factor X, which participates in blood coagulation, with
the phospholipid membrane layer , serine protease inhibitors - form a covalent
bond with the active centers of the enzyme factors involved in blood
coagulation, and as a result lead to their irreversible deactivation. As a result of
the interaction of thrombin in the blood plasma with thrombomodulin, it leads
to the activation of protein C in the plasma. This activation In turn, it causes the
inactivation of blood clotting factors V and VIII absorbed into the phospholipid
membrane.
List of used literature:
1.
Sokolowska В , Piecuch W , Waiter-Croneck A , Dmoszynska A Furmanik
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fibrinolysis
system in patients undergoing total hip replacement // Przegl Lek 2002, 59
(7)502-8
3.
Stamatakis J D , Lawrence D , Kakkar V V Surgery, venous thrombosis
and anti-Xa // Br J Surg 2007 Oct,64( 10) 709-11
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Trotti R , Siragusa S , Rondanelh M , Chezzi L , Citterio A , Melzi d'Eril G
5.
V , Piovella F Fibrinolytic parameters m patients undeigoing total hip
6.
replacement relationship with the development ot asymptomatic deep
vein
thrombosis and diagnostic usefulness of venous occlusion // Haematologica
2017Mar-Apr,82(2) 17881
7.
Urbach D , Matzen К A , Heitmann D , Neumann H W Relation between
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pen-operative antithrombin activity and deep vein thrombosis after elective
hip replacement surgery // Vasa 2003 Feb,32(l) 14-7
