HEMOSTASIS

HEMOSTASIS

• Hemostasis – Stoppage of bleeding.

• Occurs in 3 major steps –

– Vasoconstriction of damaged vessels.

– Hemostatic plug formation.

– Clot retraction & dissolution.

1. VASOCONSTRICTION:

• Initial injury results in brief period arteriolar vasoconstriction.

– Ie., Minimizing vessel diameter & slowing bleeding.

• Occurs due to reflex neurogenic mechanism.

– Augmented by “Endothelin” – Potent endothelium-derived vasoconstrictor.

• Effect is transient.

• Without activation of platelet & coagulation system, bleeding resumes.

2. FORMATION OF HEMOSTATIC PLUG:

• Occurs in 2 stages – 

– Primary hemostasis – Formation of platelet plug.

– Secondary hemostasis – Consolidation of platelet plug.

2a. PRIMARY HEMOSTASIS:

• Step for platelet plug formation.

Endothelial injury exposes highly thrombogenic subendothelial extracellular matrix.

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Allows platelet adherence/ binding to ECM collagen.

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Binding activated cell release secretory granules & its products.

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Recruits additional platelets forming “Primary hemostatic plug” (Platelet Plug).

2B. SECONDARY HEMOSTASIS:

• Step for consolidation of platelet plug.

Coagulation system is activated & thrombin is generated.

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Thrombin converts fibrinogen to fibrin.

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Ultimately forms an irreversibly fused mass of platelets, thrombin, RBCs & fibrinogen.

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Definitive secondary hemostatic plug.

3. CLOT RETRACTION & DISSOLUTION:

Clot retraction – 

• Shrinking of clot pulls wound edges together, making wound healing easier.

• Occurs due to contraction of platelets

Dissolution of clot – 

• Fibrinolysis.

• Necessary for normal blood flow restoration to healed tissue.

• Fibrinolysis is produced by plasmin.

• Activation product of fibrinolytic system.

ROLE OF ENDOTHELIUM IN HEMOSTASIS:

• Endothelial cells, 

– Promotes blood fluidity by antithrombotic properties.

– Conversely, also exhibits procoagulant activity post-injury to arrest bleeding.

PROPERTIES OF ENDOTHELIUM: 

• Includes Anti- & Pro-Thrombotic properties.

1. ANTI-THROMBOTIC PROPERTIES:

Includes – 

• Antiplatelet effects.

• Anticoagulant effects.

• Fibrinolytic effect.

• Endothelial cells maintain blood fluidity.

Vascular endothelium – 

• Smooth, coated with a layer of glycocalyx (mucopolysaccharide).

• Thus, preventing intrinsic system activation.

• Repelling clotting factors & platelets.

• Hence, preventing clotting of blood within vessels.

1a. Anti-platelet effects:

• Intact endothelium prevents platelet contact to highly thrombogenic subendothelial ECM.

– Especially collagen.

• Endothelium secretes PGI₂ & NO.

– Both are inhibitors of platelets aggregation.

• Produces ADP’ase

– Degrades ADP.

– Potent platelet stimulator.

1b. Anti-coagulant effect:

• Endothelium has membrane-bound heparin-like molecule.

– Binds with antithrombin III.

• Inactivates factor II (thrombin), IX, X, XI, XII.

– Produces thrombomodulin.

– In turn, binds to thrombin → Converting procoagulant to anti-coagulant, capable of activating protein C.

• Protein ‘C’ along with protein ‘S’ acts as co-factor.

– Results in proteolytic cleavage of factor V & VIII.

• All endothelial cells produce thrombomodulin except cerebral circulation.

– Produces “Tissue Factor Pathway Inhibitor”.

– Inactivates tissue factors VII & X.

1c. Fibrinolytic effect:

• Endothelial cells synthesize tissue-type plasminogen activator (t-PA).

– Converts plasminogen to plasmin.

– In turn, dissolving clot by breaking fibrin.

2. PRO-THROMBOTIC  PROPERTIES:

• By following effects,

2a. Platelet effects:

• Endothelial cell injury exposes highly thrombogenic subendothelial ECM.

– Allowing platelet adherence to ECM collagen.

• Due to ↑^ed Von-Willebrand factor production by endothelium.

– An essential cofactor for platelet binding to collagen.

2b. Pro-Coagulant effects:

• Endothelial cells synthesize tissue factor.

– Activates extrinsic coagulation pathway.

2c. Anti-Fibrinolytic effect:

• Endothelial cells secretes Plasminogen Activator Inhibitors (PAI’s).

– Inhibits plasminogen activator action.

– Plasmin is not produced from plasminogen → Hence, no fibrinolysis.

ROLE OF PLATELET IN HEMOSTASIS:

• Platelets play central role in normal hemostasis.

– After endothelial injury, 

• Platelets contacts subendothelial ECM (especially collagen).

Results in platelets reactions –

• Adhesion.

• Secretion.

• Platelet aggregation.

1. Adhesion:

• Platelets adhesion to extracellular matrix, mediated largely via interaction with Von-Willebrand factor (VWF).

• Acts like bridge between platelet surface receptor GP1b & exposed collagen.

2. Secretion:

• Secretes Thromboxane A₂ & Serotonin.

• Results in vasoconstriction.

3. Platelet aggregation:

• Primary platelet plug formation stabilized by,

– Coagulation system activation.

– Thrombin formation.

– Thrombin stabilizes primary platelet plug into secondary platelet plug.

• During dissolution stage, 

– Platelet contraction occurs due to contractile proteins like thrombosthenin, actin & myosin.

– Platelet contraction cause clot retraction.

– Results in easier wound healing.

Factors promoting platelet aggregation: