Hemostatic Mechanism

The hemostatic mechanism is a complex process that prevents and stops bleeding from damaged blood vessels. It involves a series of tightly regulated steps, each critical for maintaining vascular integrity.

Mechanisms

1. Vascular Spasm (Vasoconstriction)

• Immediate Response: When a blood vessel is injured, it undergoes vasoconstriction to reduce blood flow and minimize blood loss. This is a transient response.
• Mechanism: The spasm is mediated by:
  • Endothelial Factors: Endothelin, released from endothelial cells, causes smooth muscle contraction.
  • Neural Reflexes: The sympathetic nervous system may contribute to vasoconstriction.

2. Platelet Plug Formation

• Adhesion: Platelets adhere to exposed collagen fibres in the damaged vessel wall. Von Willebrand factor (vWF) bridges collagen and platelet receptors (GPIb-IX-V complex).
• Activation: Adhered platelets become activated and release granules containing:
  • ADP (Adenosine Diphosphate): Promotes further platelet activation and aggregation.
  • Thromboxane A2: A potent vasoconstrictor and platelet aggregator.
  • Serotonin: Also contributes to vasoconstriction.
• Aggregation: Activated platelets stick together through fibrinogen binding to platelet GPIIb-IIIa receptors, forming a temporary plug.

3. Coagulation (Blood Clotting)

• Coagulation Cascade: The cascade involves a series of enzyme activations leading to fibrin formation.
  • Intrinsic Pathway: Activated by damage to the vessel wall. It involves factors XII, XI, IX, and VIII.
  • Extrinsic Pathway: Triggered by external trauma. Involves tissue factor (TF) and factor VII.
  • Common Pathway: Both pathways converge to activate factor X, leading to thrombin formation, which converts fibrinogen to fibrin.
• Formation of Stable Clot: Thrombin converts fibrinogen to fibrin and activates factors V and VIII, amplifying the clotting process.

4. Clot Retraction and Repair

• Clot Retraction: Platelets contract to reduce the size of the wound, pulling the vessel edges together. This is mediated by actin and myosin in platelets.
• Repair: Platelets release growth factors (e.g., platelet-derived growth factor, PDGF) that promote tissue repair and endothelial cell proliferation.

5. Fibrinolysis

• Clot Breakdown: After vessel repair, the clot is gradually removed.
• Mechanism: Plasminogen, incorporated into the clot, is activated to plasmin, which breaks down fibrin into fibrin degradation products, leading to clot dissolution.

Blood Coagulation

1. Cascade Theory

• Concept: This theory describes coagulation as a series of sequential enzymatic reactions.
• Steps:
  • Intrinsic Pathway: Activated by trauma to the blood vessel. Factors XII, XI, IX, and VIII are sequentially activated.
  • Extrinsic Pathway: Initiated by tissue factor (TF) from damaged tissues interacting with factor VII. This pathway is faster and more direct.
  • Common Pathway: Both pathways converge to activate factor X, leading to the generation of thrombin and the formation of fibrin.
• Activation: Factors are present as inactive zymogens. Each factor activates the next in the cascade, amplifying the response.

2. Cell-Based Model

• Concept: This model integrates the roles of cellular surfaces and phases in coagulation.
• Phases:
  • Initiation: Tissue factor (TF) from damaged tissues binds with factor VII to activate factor X. This generates a small amount of thrombin.
  • Amplification: Thrombin activates platelets and factors V and VIII, increasing thrombin production.
  • Propagation: Platelets and activated factors lead to a large thrombin burst, converting fibrinogen to fibrin and forming a stable clot.
• Role of Cells: Platelets provide a surface for coagulation factor interactions, while endothelial cells release TF and other regulatory factors.

3. Modern Integrated Models

• Concept: Modern understanding integrates elements from cascade and cell-based models.
• Integration:
  • Localized Activation: Coagulation is initiated at the injury site, with localized activation of coagulation factors and platelets.
  • Dynamic Interaction: The models emphasize the interaction between coagulation factors, platelets, and endothelial cells.
  • Regulation: Includes regulatory mechanisms such as protein C and S, antithrombin, and tissue factor pathway inhibitor (TFPI) to prevent excessive clotting.