Introduction to Haemostasis

Ahmad Sh. SilmiHematologist Msc,FIBMS

Course Objectives• Identify the factors that influence the effectiveness of hemostatic

processes.• Describe the mechanisms that are involved in the arrest of blood

flow from a damaged vessel.• Identify key aspects associated with primary and secondary

hemostasis.• Explain the role of various coagulation components in hemostatic

processes.• Define the extrinsic, intrinsic, and common pathways that are

part of the coagulation cascade, identifying the coagulation factors that are associated with each pathway.

• Describe the function of various laboratory tests in evaluating hemostasis.

• Identify common coagulation disorders, their symptomology, and subsequent treatment.

• Explain the role of the prothrombin time and activated partial thromboplastin time in monitoring anticoagulation therapy.

Course outlinePart one

• An Introduction to the Fundamentals of Coagulation• Introduction to the Fundamentals of Coagulation• Which of the following would NOT impact the effectiveness of

hemostatic processes?– Primary Hemostasis

• Introduction to Hemostatic Mechanisms• Primary Hemostasis: The Vascular System and Platelet

Involvement• Primary Hemostasis: Platelet Production• Primary Hemostasis: Characteristics of the Platelet• Primary Hemostasis: Platelet Function• Summary of Primary Hemostasis• Which of the following processes does NOT occur during primary

hemostasis?

Course outlinePart one Cont.

– Overview of Secondary Hemostasis• Overview of Secondary Hemostasis• Secondary Hemostasis: Fibrin Formation via the Coagulation

Cascade• Consequences Linked to Deficiencies in Coagulation Factors• What is the ultimate goal of secondary hemostasis?• Coagulation Factors in the Coagulation Cascade• Secondary Hemostasis: The Extrinsic Pathway• Secondary Hemostasis: The Intrinsic Pathway• Secondary Hemostasis: The Common Pathway• Secondary Hemostasis: Coagulation Factor Characteristics• Factor VII is part of which coagulation pathway?

– The Fibrinolytic System• The Fibrinolytic System

• Regulation of hemostatic mechanisms

Course outlinePart Two

– Coagulation Disorders• Coagulation Disorders: Inherited• Coagulation Disorders: Acquired• Coagulation Disorders: Platelet Disorders• Coagulation Disorders and Liver Disease

– Anticoagulation Therapy• Anticoagulation Therapy• Heparin Therapy• Oral Anticoagulant Therapy• Other

Let us Begin……

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HEMOSTASIS Haemostasis or Hemostasis (Greek: aimóstasis, from aíma "blood" + stásis "stagnation") is a complex process which continually ensures: prevention of spontaneous blood loss and stops hemorrhage caused by damage of

vascular system

Most times this includes the changing of blood from a fluid to a solid state and then to fluid state.

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Function of Haemostasis

Arrests bleeding Keeps blood in fluid state Repair and reestablish the blood flow through the

injured vessels Remove haemostatic plug

If any of the above functions is exaggerated or impaired it will cause either thrombosis or hemorrhage respectively; so hemostasis is a balance between thrombosis and hemorrhage

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Without this balance, the individual may experience either Without this balance, the individual may experience either excessive excessive bleedingbleeding (poor clot formation or excessive Fibrinolysis) (poor clot formation or excessive Fibrinolysis)

Vaso-occlusion (uncontrolled formation of thrombin in vascular Vaso-occlusion (uncontrolled formation of thrombin in vascular system, occluding vessels and depriving organs of blood).system, occluding vessels and depriving organs of blood).

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HEMOSTASIS

There are certain conditions associated with excessive bleeding are referred to as: Hypo-coagulable states. Such as, Hemophilia or deficiency in one of the plasma coagulation proteins such as factors VIII. Acquired conditions such as DIC, Liver and Kidney diseases.

In addition to Coagulation promotion, vessel injury initiates Fibrinolysis through endothelial cell release of tissue Plasminogen activators (tPAS).

This is to ensure that excessive coagulation does not occur.

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HEMOSTASIS

Role of Coagulation in Hemostasis Coagulation: Is the process where by on vessel

injury, Plasma protein, Tissue factors and Calcium interact on the surface of the platelets to form a Fibrin clot.

Platelets provide a surface for the coagulation reaction, and interact with fibrin to form a stable platelet fibrin clot.

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HEMOSTASIS

Tissue factors (except Ca and Tissue Thromboplastin) normally circulate in the plasma as inactive proteins.

On activation some factors form enzymatic proteins known as Seiren Proteases that activate other specific factors in the coagulation sequence.

Other conditions are related to uncontrolled thrombosis are called Hyper-coagulable state. This is related to an appropriate formation of thrombi in the vascular vessels that occlude normal blood flow.

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Mechanism of Hemostasis

Haemostasis involves a series of delicately balanced physical and biochemical changes following an injury to a blood vessel .

As the most immediate response, the blood vessel constrict

Then platelets adhere and aggregate at the site of the injury and form a plug

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Mechanism of Hemostasis These activated platelets secretes substances that

initiate the coagulation factors which interact serially, forming a fibrin network or clot in which white cells, red cells and platelets are trapped and form a solid plug of blood ( coagulation) which seals off the injury vessel completely.

Finally slow lysis of the clot, fibrinolysis, begins and the site of the injury is repaired.

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Components of normal hemostasis vessels

Tissue Tissular coagulation factor Platelets

Thrombocytic Platelet Coagulation

factors Coagulation (activator & inhibitors)

Humoral( plasma factors) Fibrinolysis

(activater & inhibitors)

The effectiveness or failure of haemostatic mechanism to control bleeding depends on :– The type & degree of injury.– The size & ability of injured vessel to

contract.– The pressure within the vessel & surrounding

tissues.– The availability & activity of the platelets.– The quantity & functional ability of blood

clotting factors.– The absence of inhibitors.

Hemostasis

The hemostatic components remain inert in the presence of intact vascular tissue or endothelium

Following injury, each component must function optimally.

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Vessel wall, Blood flow & Coagulation Substances

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In Case if there is an Endothelial Injury(Bleeding must be prevented at site of injury)

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Flow must be Maintained

Virchow LawThere are three haemostatic components:

• 1- The extra-vascular (The tissues surrounding blood vessels) involved in Hemostasis when local vessel is injured.It plays a part in Hemostasis by providing back-pressure on the injured vessel through swelling and trapping of escaped blood.

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HEMOSTASIS

The three haemostatic components 2- The vascular (The blood vessels through

which blood flow) it depends on the size, amount, of smooth muscle within their walls and integrity of the endothelial cell lining.

3- The intra-vascular (The platelets and plasma proteins that circulate within the blood vessels).These components are involved in Coagulation (clot or thrombus formation) or Fibrinolysis (clot or thrombus dissolution).

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PhasesThree –phase process

I. Primary hemostasis

II. Coagulation (secondary hemostasis)

III. Fibrinolysis (Tertiary hemostasis)

Phases cont’dI. Primary hemostasis Involves

Blood vessels (vascular vasoconstriction phase and release of tissue or exogenous factors)

Thrombocytes (platelate or endothelial –thrombocyte phase, platelate aggregation and release of platelate factors).

After 3 to 5 minutes , blood flow is arrested with the formation of a platelate plug.

Phases cont’d

II. Coagulation Involves

Plasma coagulation factors (plasma phase) Platelate factor 3

provides for definitive hemostasis Takes 5 to 10 minutes by formation of fibrin

Reinforces the platelate plug.

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Phases cont’d

III Fibrinolysis

Essential final step in any hemostasis mechanism,

Enabling in 48 to 72 hours, and a

Return to normal by destroying fibrin and healing the injured vessel.

I. Primary hemostasis

Is a result of a three –way interaction between: Vascular wall Platelets plasma coagulation factors

Triggered by Small injuries to blood vessels The plasma coagulation factors desquamation

(damaging of epithelial cells in pinpricks)

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Primary hemostasis Involves:

VasoconstrictionPlatelet adhesionPlatelet aggregationPlatelet secretion

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HEMOSTASIS

Role of Blood Vessels in Hemostasis Blood flows through the vascular system to and

from all parts of the body. The vascular system consists of capillaries, arteries, and veins.

Blood normally carried within vessels whose physical capabilities include Contraction (narrowing) and Dilation, which are controlled by the smooth muscle of the vessel media.

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HEMOSTASIS

Vasoconstriction and Vasodilatation provide the means for control blood flow rate and blood pressure.

Substances released from the endothelial cells and sub- endothelial smooth muscles also contribute to normal blood flow and prevent abnormal formation of clot.

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Arachidonic acid

ENDOTHELIAL CELL PLATELET

Thromboxane synthetaseProstacyclin

synthetase

Cyclo-oxygenase

Prostacyclin (PGI2)

Thromboxane(TxA2)

Inhibits plt aggregationVasodilator

Enhances plt aggregationVasoconstrictor

Cyclic Endoperoxides

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Summary of Important Vascular Function

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Vascular Endothelium Function

Prostacyclin

Thromboxane A2

ELAMs, ICAMs

von Willebrand factor

Vasodilation, inhibition of platelet aggregation

From platelets, constrictmuscular arteries

Cytokines induce synthesis to promote leukocyte adhesion

Promote platelet-collagen adhesion to exposed sub-endothelium

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Vascular Endothelium FunctionTissue factor pathway inhibitor

Thrombomodulin

Tissue plasminogen activator

Heparan sulfate proteoglycans

Tissue factor

Anticoagulant- Inhibits coagulation extrinsic pathway

Anticoagulant- Inhibits coagulation by activating protein C system

Anticoagulant- Inhibits coagulation by activating fibrinolysis

Anticoagulant- Inhibits coagulation by activating antithrombin

Procoagulant- Inflammatory cytokines (IL-1, TNF) induce expression

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Upon conclusion one can aske the following question

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