Dr. Basim Al-Ka'abi
Blood Physiology
Seventh Lecture
1
Lecture Name: Hemostasis and Blood Coagulation
Lecturer Name: Dr. Basim A. Al-Ka'abi
Department: Medical Physiology
Stage: First Stage Medical Students
Lecture Objectives:
By the end of this lecture the students should be able to know the following:
Meaning of hemostasis and its mechanisms.
The extrinsic and intrinsic pathways of blood coagulation.
Blood clot retraction and fibrinolysis.
References:
Barrett, K et al. (2018). Ganong's Review of Medical Physiology. Twenty-
sixth edition. USA.
Guyton, A and Hall, J (2015). Text Book of Medical Physiology.
Thirteenth edition. Philadelphia, USA.
Dr. Basim Al-Ka'abi
Blood Physiology
Seventh Lecture
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Hemostasis and blood coagulation
-The term hemostasis means prevention of blood loss.
-Whenever a vessel is ruptured, hemostasis is achieved by several different
mechanism including:
1. Vascular spasm.
2. Formation of platelet plug.
3. Blood coagulation.
4. Growth of fibrous tissue into the blood clot to close the hole in the
vessel permanently.
Vascular spasm
-Immediately after a blood vessel is cut or ruptured, the wall of the vessel
contracts, this lead to reduce the flow of blood from the vessel rupture.
-The contraction results from both nervous reflexes and local myogenic
spasm.
Formation of the platelet plug
-Platelets repair of vascular opening is based on several important
functions of the platelet itself.
-When platelets come in contact with a damaged vascular surface, they
begin to swell, assuming irregular forms with numerous irradiating
processes protruding from their surfaces.
-They become sticky so that they stick to the damaged vascular surface,
and these accumulations of platelet lead to the formation of a platelet plug.
-This is a loose plug, but it is usually able to stop the blood loss if the
vascular opening is small.
Dr. Basim Al-Ka'abi
Blood Physiology
Seventh Lecture
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Blood coagulation
-This takes place in three essential steps:
A- Thromboplastin formation via the extrinsic and intrinsic systems.
B- Thrombin formation.
C- Fibrin formation.
Formation of thromboplastin (prothrombin activator)
-There are two basic ways in which thromboplastin can be formed:
(1) Extrinsic pathway: Begins with trauma to the vascular wall or to the
tissue outside the blood vessels.
(2) Intrinsic pathway: Begins in the blood itself.
-In both these pathways, a series of different plasma proteins, especially
beta globulins, play major roles. These are called the clotting factors.
The extrinsic mechanism for initiating clotting
-This mechanism occurs according to the following three basic steps:
(1) Release of tissue factor and tissue phospholipids:
-The traumatized tissue releases two factors that set the clotting process
into motion. These are:
a. Tissue factor: Which is a proteolytic enzyme.
b. Tissue phospholipids: From the tissues and cell membrane.
Dr. Basim Al-Ka'abi
Blood Physiology
Seventh Lecture
4
(2) Formation of activated factor X
-The tissue factor complexes with blood coagulation factor VII and this
complex, in the presence of tissue phospholipids, act enzymatically on
factor X to form activated factor X.
(3) Formation of prothrombin activator
-The activated factor X complexes immediately with the tissue
phospholipids released from the traumatized tissue and also with factor V
to form a complex called thromboplastin (prothrombin activator).
The intrinsic mechanism for initiating clotting
-This mechanism occurs according to the following steps:
(1) Activation of factor XII and release of platelet phospholipids
-When factor XII comes into contact with collagen, it takes out a new
configuration that converts it into a proteolytic enzyme called activated
factor XII.
-The blood trauma also damages the platelets, and this lead to the release
of platelet phospholipids that is called platelet factor III.
(2) Activation of factor ХΙ
-The activated factor XII acts enzymatically on factor XI to activate it.
(3) Activation of factor ΙХ
-The activated factor ХΙ then acts enzymatically on factor ΙХ to activate it.
(4) Activation of factor Х
-The activated factor ΙХ, acting with factor VШ and with the platelet
phospholipids from traumatized platelet, activates factor Х.
Dr. Basim Al-Ka'abi
Blood Physiology
Seventh Lecture
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(5) Formation of prothrombin activator
-In this step the activated factor Х combines with factor V and platelet
phospholipids to form thromboplastin.
-Then it will act within seconds to cleave prothrombin to form thrombin.
Thrombin formation (conversion of prothrombin to thrombin)
-Prothrombin is a plasma protein, an unstable protein that can easily split
into smaller compounds, one of which is thrombin, under the effect of
thromboplastin.
Conversion of fibrinogen to fibrin
-Thrombin is a protein enzyme with proteolytic activity.
-It acts on fibrinogen to form a molecule of fibrin monomer, which has the
automatic capability of polymerizing with other fibrin monomer
molecules.
-Therefore, many fibrin monomer molecules polymerize within seconds
into long fibrin threads that form the reticulum of the clot.
-In the early stages of this polymerization, the fibrin threads are not cross-
linked with each other and the resultant clot is weak and can be broken
easily.
-So another process occurs during the following few minutes that greatly
strength the fibrin reticulum. This involves a substance called fibrin-
stabilizing factor (FSF) that is normally present in small amounts in
plasma.
-Before FSF can act, it must itself be activated, then this activated FSF act
to form covalent cross linked bonds between the adjacent fibrin threads.
-The fibrin threads adhere to the damaged surfaces of blood vessels,
forming the blood clot, which is composed of a meshwork of fibrin threads
Dr. Basim Al-Ka'abi
Blood Physiology
Seventh Lecture
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running in all directions and entrapping blood cells and plasma becomes
adherent to any vascular opening and thereby prevents blood loss.
Clot retraction
-Within few minutes after a clot is formed, it begins to contract and usually
expresses most of its fluid within 30-60 minutes. This fluid expressed is
called the serum, because its fibrinogen and most of the other clotting
factors had been removed.
-Platelets are necessary for clot retraction to occur, therefore, clot retraction
will fail if the number of platelets in the circulating blood is low.
-As the clot retracts, the edges of broken blood vessel are pulled together.
Fibrinolysis
-It is the physiological process of removing unwanted fibrin deposits, in
which the liquefaction of a fibrin clot is achieved by splitting a small
number of peptide bonds of fibrin to form soluble fragments.
-The fibrinolytic system is mediated mainly by the enzyme plasmin, which
acts on fibrin to produce lysis of the clot.
-Plasmin is generated from an inactive form called plasminogen.
-These fragments are then removed from the circulation by the
macrophages of the reticulo-endothelial system.
-This action of the fibrinolytic system re-establishes blood flow in the
vessels occluded by a thrombus.