Chapter 25 (Hemostasis & Vascular System)

Hemostasis

A complex process that maintains the balance of blood in the fluid state in normal condition. While promoting clotting when injuries are occurred in the blood vessels

Vascular System

• Endothelial linings and vessel wall

• Regulates vessel constriction and initiates primary clotting

Platelets System

• Form primary plug for primary hemostasis

• Release procoagulant compounds

Coagulation System

• Cascade activation of clotting factors

• Produces fibrin to stabilize platelet plug

Fibrinolytic System

Dissolved clots once injury is healed involving plasmin that degrades fibrin

Serine Protease Inhibitors (Anticoagulant System)

• Regulate coagulation to prevent excessive clotting

Primary Hemostasis

1. Platelets Adhesion

   • Damaged vessel exposed collagen

   • Von Willebrand factor (vWF) adheres to the collagen

   • Platelets bind to vWF via GPIb receptor, to be able to anchor to the damaged vessel

2. Platelets Activation

   • Platelets change into spheres with pseudopods

   • Then procoagulant compounds get released to recruit more

   • the compounds activate GPIIb/IIIa receptors

3. Platelet Aggregation

   • Fibrinogen connects to GPIIb/IIIa

   • The end goal is temporary platelet plug forms

Secondary Hemostasis

1. Coagulation Cascade

   • Both extrinsic & intrinsic pathway occurs which converge into common pathway

   • Ultimately produces factor Xa, that convert prothrombin (factor II) → thrombin (factor IIa)

2. Fibrin Formation

   • Thrombin converts fibrinogen to fibrin

   • Form a mesh around the platelet plug

   • The end goal is Factor XIII cross-links fibrin strands to form stable fibrin clot

Fibrinolysis

• Plasminogen is incorporated into the clot and transformed into plasmin by tissue plasminogen activator (t-PA) and other factors

• Plasmin breaks down fibrin to soluble fragments dissolving the clots

• The end goal is to promote vascular healing via Platelet-Derived Growth Factor (PDGF)

Vessel Layer

Superficial → Deep

• Tunica adventitia: tissue support (anchors, protects, & repairs vessels)

• Tunica media: control vasoconstriction & vasodilatation

• Tunica intima: prevent blood clotting by providing smooth surface that keeps platelets from sticking

• Subendothelial surface: beneath the intima where vWF binds to collagen for platelet adhesion

Intact Endothelium

• Nonthrombogenic: inhibits platelets aggregation by prostacyclin (PGI₂)

GPIb/IX/V

Glycoprotein receptors on the platelets that grabs onto vWF so platelets can adhere to the wall

GPIIb & GPIIIa

Glycoprotein receptors on the platelets that fibrinogens connect and form a bridge between multiple platelets to form a plug

Thromboxane A2 (TXA2) & Serotonin

Release by platelets to further promote vasoconstriction

Petechial Hemorrhage

Pinpoint red/purple spots from small vessels break and blood leaks out. Occurs in:

• Capillary

• Arteriole (vessel from artery to capillary)

• Venule (vessel from vein to capillary)

Ecchymosis

Large flat area of soft tissue bleeding. Occurs in:

• Veins

Rapid Blowout Hemorrhage

High pressure rupture that requires urgent intervention. Occurs in:

• Arteries

Extrinsic Pathway

1. Tissue factor (Factor III) is exposed and released from damaged cells

2. Factor III binds to factor VII

3. Factor VII becomes VIIa

4. Activates factor X

Intrinsic Pathway

• Clotting factors that are present within the blood

• Tissue Factor XII → XI → IX → VIII

Prostacyclin (PGI₂) {Role, Function}

• Anticoagulant

• Synthesized by endothelial cells, inhibits platelet aggregation & limits thrombus formation beyond damage vessels

Tissue Plasminogen Activator (t-PA) {Role, Function}

• Fibrinolytic

• Enzymes secreted by endothelial cells. Activate plasminogen to plasmin

Tissue Factor Pathway Inhibitors (TFPIs) {Role, Function}

• Anticoagulant

• Glycoproteins on endothelial surfaces that limit the extrinsic pathway from spreading beyond injured area. Achieved by inhibit factors VIIa & XA

Heparan Sulfate {Role, Function}

• Anticoagulant

• Glycosaminoglycan on the surface of endothelial cells, enhances antithrombin activation

Thrombomodulin & Protein C Receptor {Role, Function}

• Anticoagulant

• Protein on surface of endothelial cells that bound thrombin to activate Proteins C (anticoagulant) rather than letting thrombin activates fibrinogen

• Protein C receptor bind protein C and present it to thrombomodulin to improve efficiency

Injured Endothelial Lining {Role, Function}

• Coagulant

• Promotes vasoconstriction

Collagen {Role, Function}

• Coagulant

• Binds vWf at the site of injury

Von Willebrand Factor (vWF) {Role, Function}

• Coagulant

• Binds GP Ib/IX/V and collagen enabling platelets adhesion to the vessel walls. Under high shear stress, can bind GP IIb/IIIA

• Side function: supports intrinsic pathway by transporting factor VIII and protecting it from degradation

Tissue Factor (Factor III) {Role, Function}

• Coagulant

• Lipoproteins released from vessel injury, initiates extrinsic pathway by activating factor VII with calcium.

Plasminogen Activator Inhibitors (PAIs) {Role, Function}

• Antifibrinolytic

• Prevent excessive clotting by neutralizing t-Pa (reduce plasmin)

Normal Platelet Count

150 to 450 × 10⁹ per liter of blood