NAME OF INSTITUTION : RAM MEDICAL TRAINING COLLEGE.

ADM NO :669/2023

UNIT : BLOOD AND LYMPHATIC DISORDERS.

ASSIGNMENT : THE STEPS IN THE PROCESS OF HEMOSTASIS, COAGULATION

AND COMPARISON BETWEEN HEMOSTASIS AND COAGULATION.

LECTURER : MR. JEFFERSON OMBOGA.

STEPS IN THE PROCESS OF HEMOSTASIS :

Hemostasis is the process in which the body repairs a damaged blood vessel
to prevent the further loss of blood.

Hemostasis involves the formation of a blood clot (thrombus) that prevents

further blood loss from damaged tissues, blood vessels or organs.

The bleeding of injured blood vessels is brought to a halt through the process
of hemostasis.

The process of hemostasis has two phases:

a). Primary hemostasis - which involves platelet plug formation .

b). Secondary hemostasis - which involves blood coagulation.

Hemostasis relies on blood cells (primarily platelets), plasma proteins,

endothelial cells, and plasma glycoproteins such as von Willebrand factor
(vWF).
Factors That Inhibit Clot Formation

[Link] C, protein S and thrombomodulin form a complex group of proteins

that can inactivate factor VIII and factor V.

[Link] protein C, protein S and thrombomodulin complex is activated by

thrombin.

[Link] where it blocks the actions of multiple clotting factors

called inhibition.

Factors That Promote Clot Formation

[Link] V and factor VIII accelerate the conversion of factor X to factor Xa by

factor IXa and accelerate the conversion of prothrombin to thrombin as done
by factor Xa.

Hemostasis Steps

Hemostasis can be broken down into two phases

[Link] hemostasis - Involves the formation of a platelet plug.

2. Secondary hemostasis - Involves the coagulation process and the

formation of a blood clot, commonly referred to as a thrombus.
 Functionally, hemostasis is comprised of various hemostasis stages after a
vessel injury.

Hemostasis stages:

a). Blood vessel spasm

b). Platelet plug formation

c). Coagulation process and blood clot formation

The excess or unrequired blood clots are removed through a process called
fibrinolysis.

A) Blood vessel spasm

A blood vessel experiences a vascular spasm which is sudden and shortened

tightening of the vessels caused by its smooth muscles within 30 minutes
following its injury or trauma.

This leads to vasoconstriction, which limits the blood flow to the injured area
by blocking small blood vessels such as arterioles and small arteries.

The injury causes the lining of the blood vessels to expose their collagen
(structural proteins of a blood vessel wall) to the blood cells.

B) Platelet Plug Formation

Platelet plug formation involves the adhesion and aggregation of activated

platelets at the injury site.
●Firstly, platelets bind to the exposed collagen, and this process is aided by
the von Willebrand factor(vWF).

vWF is a plasma glycoprotein that allows the flowing platelets to adhere to

the walls of blood vessels. This binding leads to the activation of the
platelets.

●Secondly the activated platelets release granules, which contain several

factors, some of which enhance coagulation (blood becoming thicker, almost
like gel).

Factors released from platelet granules include ;

●Thromboxane A2,

●Serotonin

●Adenosine phosphate (ADP)

● Epinephrine.

Adenosine phosphate recruits more platelets to the injured site and

releasing granules.

Activated platelets also increase the expression of their surface proteins,

such as the glycoprotein complex.

Serotonin maintains vasoconstriction.

This complex binds to a soluble plasma protein known as fibrinogen, leading

to cross-links between numerous platelets. Ultimately, the injured site gets
dominated by layers of activated platelets that eventually form a platelet
plug.
A platelet plug closes the opening of the blood vessel wall, thus reducing
further blood loss.

This plug is then strengthened by fibrin, a strong and insoluble polymer that
forms a mesh intended to trap circulating blood cells.

C) Coagulation process and blood clot formation

Coagulation is the process of forming a blood clot.

The plasma protein fibrinogen is converted into a non-globular and insoluble

protein called fibrin.

Fibrin is created in threads, which results in a mesh that traps platelets and
erythrocytes that travel through it and the final product is a gelatinous and
durable clot.

Coagulation is often described as a cascade, as one event will prompt the

next step in the process

In this cascade, chemicals known as clotting factors initiate the activity of

additional clotting factors.

The process can be divided into the extrinsic and intrinsic pathways.

The extrinsic pathway is normally triggered by trauma while the intrinsic

pathway is triggered by internal damage to the vessel walls.
Both of these pathways merge into a third known as the common pathway.

Disorders Involving Blood Clotting

[Link] - which results due to the inability of blood to form

clots.

This can lead to excessive bleeding, even from minor wounds.

2. Thrombocytosis - the body produces too many platelets which can lead to
strokes or a heart attack.

STEPS IN PROCESS OF COAGULATION

Coagulation is the process of changing of blood from a liquid to a gel or

solid, that results in the formation of a blood clot

Coagulation begins almost instantly after an injury to the endothelium that

lines a blood vessel.

Exposure of blood to the subendothelial space initiates two processes:

changes in platelets, and the exposure of subendothelial platelet tissue
factor to coagulation factor VII, which ultimately leads to cross-linked fibrin
formation.

Coagulation can be initiated by either of two distinct pathways.

[Link] Intrinsic pathway - which can be initiated by events that take place
within the lumen of blood vessels.
 The Intrinsic pathway requires only elements found within, or intrinsic to the
vascular system.

[Link] Extrinsic pathway - is the other route to coagulation.

It requires Tissue Factor (tissue thromboplastin), a substance which is

"extrinsic to", or not normally circulating in the vessel.

●Tissue Factor is released when the vessel wall is ruptured.

The steps of coagulation

are discussed under the three subsections:

[Link] factors & platelets create a plug

[Link] recruit

[Link] coagulation cascade

1. CLOTTING FACTORS

Are proteins that aid in the blood coagulation process.

Clotting factors are proteins found in the blood plasma that work together to
stop bleeding by forming a clot.

The twelve coagulation factors

[Link] I - fibrinogen

[Link] II - prothrombin

[Link] III - tissue thromboplastin (tissue factor)

[Link] IV - ionized calcium ( Ca++ )

[Link] V - labile factor or proaccelerin

[Link] VII - stable factor or proconvertin

[Link] VIII - antihemophilic factor

[Link] IX - plasma thromboplastin component, Christmas factor

[Link] X - Stuart-Prower factor

[Link] XI - plasma thromboplastin antecedent

[Link] XII - Hageman factor

[Link] XIII - fibrin-stabilizing factor

Many clotting factors rely on vitamin K to function.

A lack of vitamin K can cause problems with blood clotting, this is due to the
fact that Vitamin K aids in the conversion of certain clotting factors into their
mature forms, which helps to regulate the process of blood coagulation.

It is so important to the blood-clotting process that it has earned the name

"the clotting vitamin."

2. PLATELETS

Are fragments of megakaryocytes, which are very large cells in the bone
marrow.

They are the cells necessary in blood coagulation for vessel repair and
clotting because they form the initial platelet plug

Platelets form the "platelet plug", which forms almost immediately after a
blood vessel is ruptured.
The inner surface of blood vessels is lined with a thin layer of cells called
endothelial cells that produce chemical messengers which inhibit platelet
activation in normal conditions.

When the endothelial layer is damaged, collagen is exposed, releasing other

factors into the bloodstream.

This attracts blood platelets circulating in the blood to travel to the wound
and stick together.

When platelets are activated, they clump together to form a platelet plug,
releasing various compounds that cause even more platelets to aggregate to
aid in wound closure.

A seal is usually formed within a few minutes. This seal is a first-aid measure
to stop the bleeding.

Platelets, however, cannot close the hole on their own,

there are proteins in blood plasma that react to convert fibrinogen, a water-
soluble protein found in blood serum, into fibrin, a non-water-soluble protein
that strengthens the platelet plug.

As a result, a blood clot composed of platelets, fibrin, and blood cells forms
the plug or clot stays in place for several days, preventing blood loss.

3. COAGULATION CASCADE

The coagulation cascade is a series of reactions, catalysed by protein

enzymes known as coagulation ‘factors’.
When activated, these factors trigger the conversion of other factors in the
coagulation cascade resulting in secondary haemostasis.

Secondary haemostasis refers to the stabilisation of activated platelets due

to the actions of strands of fibrin. Which later forms a clot.

The activation and adherence of platelets to the damaged endothelium and

vascular response to injury e.g. vasoconstriction are the other key
components involved in thrombus formation and haemostasis.

Fibrin is converted from its precursor fibrinogen by thrombin and is the end-
product of the chain of reactions that make up the coagulation cascade.

The coagulation cascade can be divided into three segments or pathways:

1. The intrinsic

2. Extrinsic

3. common pathways.

[Link] extrinsic pathway

Initiation of the coagulation cascade is usually mediated by tissue factor via

the extrinsic pathway.

Tissue factor is expressed on the surface of many cells found outside blood
vessels but not on the surface of circulating blood cells or the endothelium.

When the endothelium is damaged, tissue factor comes into contact with
blood and combines with circulating factor VII to form a complex that leads
to the activation of factor X, triggering the common pathway.

[Link] intrinsic pathway

The intrinsic pathway can be activated by surface contact, when damage to
the vascular endothelium leads to exposure of clotting factors to negatively
charged subendothelial surfaces, mediated by the molecule Kallikrein.

Within blood vessels, thrombin generated from previous activation of the

extrinsic pathway also activates the intrinsic pathway.

The series of reactions in the intrinsic pathway leads to initiation of the

common pathway and therefore amplification of thrombin production through
the creation of a positive feedback loop.

Reactions in the intrinsic pathway :

Surface contact activates factor XII

Factor XIIa activates factor XI

Factor XIa activates factor IX

Factor IXa combines with factor VIIIa, platelet membrane phospholipid and
Ca2+ ions to activate factor X

Factor Xa activates the common pathway generating more thrombin

This continuous cycle means that vast amounts of thrombin can be

generated from a single initial stimulus and a thrombus can be formed
quickly after injury to limit blood loss.

[Link] common pathway

The common pathway begins with activation of factor X to factor Xa via

either the extrinsic pathway or the intrinsic pathway.

It is the final stage of the coagulation cascade and leads to the formation of
thrombin and fibrin.
Factor Xa combines with factor V, platelet membrane phospholipids and
Ca2+ ions to convert prothrombin into thrombin.

Thrombin then converts fibrinogen into fibrin strands which form an

important structural component of a thrombus.

COMPARISON AND CONTRAST BETWEEN HEMOSTASIS AND COAGULATION.

[Link] is the overall process of arresting bleeding following a vascular

injury, whereas Coagulation is the final step of hemostasis in which a stable
blood clot is formed by platelets and insoluble fibrin network.

[Link] ultimate result of the hemostasis is the stoppage of bleeding. whereas

during the coagulation soluble plasma fibrinogen polymerizes into insoluble
fibrin and forms a plug to block the hole made by the injury.

[Link] can be categorized into two types named primary hemostasis

and secondary hemostasis. whereas Coagulation can be categorized
into intrinsic pathway of blood clotting and extrinsic pathway of blood
clotting.

[Link] can show abnormalities due to platelet disorders, whereas

Coagulation can be impaired by disorders of the liver and inactive or
abnormal fibrinogen production.

Referrences:

Anatomy and physiolgy, Ross and Willson,

http//[Link],

http//[Link].