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
4
Listening
