W10 Haemostasis Flashcards by Sharjeel Ahmad

Haemostasis

Protective process evolved in order to maintain a stable physiology

“An explosive reaction designed to curtail blood loss, restore vascular integrity and ultimately preserve life”

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DIC

disseminated intravascular coagulation

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The Horseshoe Crab

Limulus Polyphemus

‘A primitive coagulation pathway can be initiated by endotoxin’

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The Haemolymph contains amebocytes:

Proteins of the coagulation system

Proteins & peptides of the immune system

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Life preserving processes designed to maintain blood flow

Respond to tissue injury
Curtail blood loss
Restore vascular integrity & promote healing
Limit infection

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Four Key Components

Endothelium
Coagulation
Platelets
Fibrinolysis

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What makes a Blood Clot?

Fibrin mesh
Platelets
Red blood cells

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Haemostasis simplified steps

Tissue injury
Vasoconstriction
Platelet activation
Haemostatic plug
Coagulation
Stable clot formation
Clot dissolution

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Primary haemostasis:

Vasoconstriction (immediate)
Platelet adhesion (within seconds)
Platelet aggregation and contraction (within minutes)

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Secondary haemostasis:

Activation of coagulation factors (within seconds)

Formation of fibrin (within minutes)

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Fibrinolysis:

Activation of fibrinolysis (within minutes)

Lysis of the plug (within hours)

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The vessel Wall

Normal Endothelium:
	- inhibits coagulation
	- prevents platelet aggregation
Provides a barrier to reactive elements in the subendothelium
	- collagen fibronectin
	- tissue factor

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Haemostasis at rest

triggers and cofactors separated

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Von Willebrand Factor: functions

Forms a bridge between damaged vessel wall (collagen) and platelets
(primary haemostasis)

Stabilises and protects Factor VIII from rapid clearance

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Loss of VWF function

results in a bleeding disorder

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VWF synthesis and storage

Synthesis
Endothelial cells
Weibel Palade bodies

Megakaryocytes
Platelet a granules

Plasma VWF entirely derived from endothelial cells

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Distribution of VWF

Constitutive path (95%)
Regulated path (5%)

Weibel-Palade bodies (storage granules of endothelial cells)

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Platelet activation

Resting Platelet
Activation
Adhesion + spreading

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When a vessel wall is damaged

various signalling molecules are expressed / exposed, including tissue factor and collagen

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Initiation of coagulation

The TF leads to the production of a small local amount of thrombin, which is the initiation step of the coagulation process

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Adhesion

The exposed signalling molecules attract circulating platelets, which attach themselves to the exposed sub-endothelial tissue

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secretion

These platelets become activated – principally through the presence of the thrombin – and release further attractant chemicals, which attract more platelets

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Aggregation

These new platelets bind to the adhered platelets and themselves become activated

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contraction

Study These Flashcards

Through the conformational changes inherent in activation, the loose platelet plug contracts to form a dense, adherent plug

activated platelets also present a substantial area of...

of negatively-charged phospholipid membrane at the site of the injury, upon which the subsequent processes of coagulation (secondary haemostasis) can occur, if needed

Fibrin mesh

Fibrin mesh binds and stabilises platelet plug and other cells

Fibrinogen (I)

Forms clot (fibrin)

Prothrombin (II)

Its active form (IIa) activates I, V, VII, XIII, protein C, platelets

Tissue factor (III)

Co-factor of VIIa

Calcium

Required for coagulation factors to bind to phospholipid (formerly known as factor IV)

V (proaccelerin, labile factor)

Co-factor of X with which it forms the prothrombinase complex

Unassigned - old name of Factor Va

VII (stable factor)

Activates IX, X

VIII (antihaemophilic factor)

Co-factor of IX with which it forms the tenase complex

IX (Christmas factor)

Activates X: forms tenase complex with factor VIII

X (Stuart-Prower factor)

Activates II: forms prothrombinase complex with factor V

XI (plasma thromboplastin antecedent)

Activates XII, IX and prekallikrein

XII (Hageman factor)

Activates prekallikrein and fibrinolysis

XIII (fibrin-stabilizing factor)

Crosslinks fibrin

von Willebrand factor

Binds to VIII, mediates platelet adhesion

FVII deficiency

FVII deficiency causes bleeding

FXII deficiency

FXII deficiency not associated with bleeding

Tissue Factor drives coagulation

TF is outside the lumen Formation of TF-FVIIa complex Recruitment of FX and formation of thrombin

Initiation of coagulation occurs when

occurs when sub-endothelial tissue is exposed to the circulation at a site of injury. These tissues express tissue factor at their surface, which binds to endogenous activated FVII

This complex binds

complex binds small amounts of FX and FV to the exposed endothelial surface, which produce small quantities of thrombin

The thrombin activates

activates platelets that are attracted to the site by the process, as well as other plasma-borne clotting factors

The activated factors (among them FVIII and FIX) enable the binding of ?

enable the binding of activated FX and FV to the surface of platelets whose activation has produce conformational changes in their surface membranes to expose the ‘reaction sites’ necessary for continuation of the process

the ‘thrombin burst’

This leads to the ‘thrombin burst’ that is necessary for the large-scale production of fibrin and so the development of an effective clot

coagulation phases

These three stages are called the initiation, amplification and propagation phases of coagulation

Fibrinolysis

Main function clot limiting mechanism repair and healing mechanism Series of tightly regulated enzymatic steps Feedback potentiation & inhibition Main Key players Plasminogen Tissue plasminogen activator (t-PA) & urokinase (u-PA) Plasminogen activator inhibitor -1 and -2 α2-plasmin inhibitor

Plamin formation

Plasminogen to plasmin through tPA (tissue plasminogen activator)

D dimers

D dimers are generated when cross-linked fibrin is degraded.

FDP (Fibrin degradation products)

FDP (Fibrin degradation products) are generated if non-cross linked fibrin or fibrinogen is broken down

tPA and a bacterial activator used for..

tPA and a bacterial activator, streptokinase, are used in therapeutic thrombolysis for myocardial infarction (Clot busters) and stroke

During thrombosis what increases/decreases

Coagulation factors + platelets increase Fibrinolytic factors, anticoagulant proteins decrease

Chronic venous insufficiency

Atrophic changes Hyperpigmentation Ulceration Infection

During bleeding what increases/decreases

Coagulation factors + platelets decrease Fibrinolytic factors, anticoagulant proteins increase

Easy bruising | ecchymosis

Virtually all bleeding disorders and often in normals

W10 Haemostasis Flashcards

(58 cards)