Hemostasis Lecture Notes

Definition

• Hemostasis: Prevention of blood loss.
  • Derived from Greek:
    - ‘hemo’ means blood
    - ‘stasis’ means stagnation

Three Stages of Hemostasis

1. Vasoconstriction
2. Platelet Plug Formation
3. Coagulation

Detailed Process

1. Vasoconstriction

• Purpose: Prevents blood loss by narrowing blood vessels.
• Mechanisms:
  1. Endothelin Release: Ruptured endothelial cells release endothelin, a vasoconstrictor.
  2. Nerve Reflexes: Triggered by pain from the injury.
  3. Local Myogenic Response: Direct contraction response to injury.

2. Platelet Plug Formation

• Components: Platelets, von Willebrand factor, clotting factors.
• Process:
  1. Platelet Adhesion:
     • Von Willebrand factor binds to collagen in damaged vessel.
     • Platelets attach to von Willebrand factor via glycoprotein 2B receptor.
  2. Platelet Activation:
     • Activated platelets secrete ADP, thromboxane A2, serotonin.
  3. Platelet Aggregation:
     • Substances activate more platelets to adhere.
  4. Formation of Platelet Plug: Helps block bleeding temporarily, but not firm enough and need to be repaired completely using the next step.

3. Coagulation

• Purpose: Repairs vessel with a firm blood clot.
• Clothing factors involved: Prothrombin, fibrinogen.
  This leads to the formation of prothrombin activator prothrombin activator catalyzes the conversion of prothrombin into thrombin, thrombin acts on fibrinogen causing polymerization of its molecules into fibrin fibers, fibrin fibers form a mesh work running in all directions and trapping blood cells and platelets and this makes the final blood clot
• Two Pathways for initiation of clothing.
  1. Extrinsic Pathway:
     • Initiated by trauma to vascular wall releasing tissue factor (factor 3).
     • Forms prothrombin activator tissue Factor combines with Factor 7 in the presence of calcium to form factor 7 tissue Factor complex this tissue factor factor 7 complex acts and enzymatically on Factor 10 to form activated Factor 10. the activated Factor 10 combines with tissue phospholipids that are a part of tissue factor to form a complex called prothrombin activator it is called extrinsic pathway because it is activated by tissue factor that normally does not belong to plasma, and occurs outside the vascular wall.
  2. Intrinsic Pathway:
     • Traumatized blood vessel activates factor 12 which causes an enzymatic process leading to a cascade of factor activations (11, 9, 8) in the presence of calcium to activate factor 10.
     • This step will be deficient if factor 8 is in short supply
     • Factor 8 deficiency leads to hemophilia (anti-hemophilic factor).
       It is called Intrinsic pathway because the entire cascade of clothing factors is intrinsic to blood.
• Final Clot Formation:
  • Thrombin converts fibrinogen into fibrin fibers forming a mesh.
  • Entrapped platelets activate contractile proteins (thrombosthenin, actin, myosin) for clot retraction, causing the edges of blood vessels to be pulled together. Contributing further to Hemostasis

Important Points

• Vasoconstriction: Immediate response to vessel injury.
• Platelet Plug: Temporary solution before clot formation.
• Clot Formation: Stabilizes vessel repair.
• Clotting Pathways: Ensure proper clot formation; each pathway is essential for specific circumstances.

Clinical Relevance

• Hemophilia: Often due to factor 8 deficiency affecting the intrinsic pathway.