Coagulation

PRESENTED BY U A.ALBORAI

Wednesday, Dece
mber 08, 2021

1
 Blood coagulation
Biochemical reactions that involve activation
of clotting factors( present in the blood in
inactive form) in cascade way to form the
blood clot
Activation of these factors occurs by :
- Intrinsic pathway
- Extrinsic pathway
Both reactions are calcium dependent
 injury

Intrinsic pathway Extrinsic pathway

Common pathway

Blood clot
Intrinsic pathway
-All factors involved are present in the blood
-Activation does not need tissue factor
-It occurs when blood comes in contact with:
- collagen
- Wettable negative surface (e.g. glass)
Extrinsic pathway
-A tissue factor (thromboplastin) is needed
for its activation

-More faster than intrinsic pathway

Stabilization of the clot:
thrombin

XIII Active XIII

Fibrin Stable clot

stabilization
The clot retract pulling the edges of the wound
together
Anticlotting Mechanisms
 Fibrinolysis
Plasminogen
Extrinsic: t-PA, urokinase
Activation
Intrinsic: factor XIIa, HMWK, kallikrein

Exogenous: streptokinase

Fibrin, fibrinogen

Plasmin

Fibrin, fibrinogen
degradation products
 HEMOSTASIS
Primary Hemostasis
-Blood vessel contraction
-Platelet Plug Formation
Secondary Hemostasis
-Activation of Clotting Cascade
-Deposition & Stabilization of Fibrin
Tertiary Hemostasis
-Dissolution of Fibrin Clot
-Dependent on Plasminogen Activation
anticoagulants
Natural anticoagulants:
Present naturally within the body ,they prevent
clotting within the circulating
They include:
 The normal endothelium:- prevent clotting by:-
- smooth surface
- release of prostacycline ( a prostaglandin cause
vasodilatation and inhibits platelet aggregation)
- release (NO), it inhibit platelet activation and
promote vasodilatation
- have plasminogen receptors on their surface
The blood flow
- Rapid blood flow inhibits coagulation whereas stasis
of blood favors coagulation

Antithrombin III
- an alpha globulin synthesized by liver
- inactivates IX, X, XI and XII
- its activity is increased about 1000times by heparin
(for this called the heparin cofactor)

- Hb may also facilitate the activity of antithrombin

Heparin
- Sulfated polysaccharide (MWt 15,000-18,000)
- Found in the granules of mast cells and basophils
- Acts through activation of antithrombin III

- Its low level in plasma indicates that it is not very

important as a natural anticoagulant at normal condition
- Its very important for prevention of coagulation when
given IV in therapeutic doses (e.g. in cases of deep vein
thrombosis (DVT))

- When given accidentally in toxic doses, protamine

sulphate is used to neutralize it
Thrombomodulin
- A protein expressed on surface of most endothelial
cells (except those in cerebral capillaries)
- Bind thrombin to form a complex that activates
protein C

Protein C and protein S

- produced by liver
- Require vit K for their synthesis
- Inactivate factor V &VIII And inhibitor of
Plasminogen activator ( increase plasmin)
Fibrin:
absorbs some clotting factors and this prevents
propagation of the clot within blood vessel

Plasmin:
breaks down fibrin resulting in dissolution of clots

Fibrin degradation products (FDPs):

inhibit coagulation by inhibit thrombin
Synthetic anticoagulants
Vitamin K antagonist:
- For example warfarin (coumarin derivative)

- Interferes with the action of vit K that need

for synthesis of clotting factors in liver ( II,
IX, VII, X)

- Warfarin is the only anticoagulants that can

be taken orally
Warfarin: Mechanism of Action

Vitamin K

VII Synthesis of
Vitamin K Utilization Dysfunctional
Reduced IX Coagulation

X
Factors

II

Warfarin
Calcium chelating agents:
This include:-
oxalate, citrate and EDTA
-They inhibit coagulation by binding calcium, making
it unavailable for coagulation
- Can not be use in vivo because this decreases
calcium concentration in plasma resulting in
tetany
Note:
Anticoagulants used only in vitro:
calcium chelating agents

 Anticoagulants used only in vivo: vit

K antagonist

Anticoagulants used in vivo and in

vitro: Heparin
Abnormalities of Hemostasis
THANKS
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