Hemostasis Lecture Notes

Introduction to Hemostasis

• Definition: Hemostasis is the process of stopping bleeding or keeping blood within a damaged blood vessel.
  • Hemo: Blood
  • Stasis: Stop
• Occurs when blood vessels are damaged (ruptured or lacerated).

Natural Anti-Coagulation Mechanisms

• Endothelial Cells: Secrete chemicals to keep blood naturally thin.
  • Nitric Oxide & PGI2 (Prostacyclin): Inhibit platelet activation and binding.
• Heparin Sulfate: A glycosaminoglycan that binds antithrombin 3, inactivating clotting factors 2, 9, and 10.
• Thrombomodulin: Binds thrombin, activating protein C which degrades factors 5 and 8.

Five Steps of Hemostasis

1. Vascular Spasm

   • Purpose: Reduces blood flow by vasoconstriction.
   • Mechanisms:
     • Endothelin: Secreted by damaged endothelial cells, causing vasoconstriction.
     • Myogenic Mechanism: Direct injury causes smooth muscle contraction.
     • Nociceptor Activation: Pain reflex causes vasoconstriction.

2. Platelet Plug Formation

   • Von Willebrand Factor: Released by damaged endothelial cells.
   • Platelet Activation: Platelets bind via glycoprotein 1B to VWF and start aggregating.
   • Chemical Release:
     • ADP & Thromboxane A2: Stimulate further platelet aggregation.
     • Serotonin: Causes vasoconstriction.
   • Platelet Aggregation: Platelets form a plug at the injury site.

3. Coagulation Cascade

   • Intrinsic Pathway: Involves factors 12, 11, 9, 8, and leads to activation of factor 10.
   • Extrinsic Pathway: Initiated by factor 3 (tissue factor) and factor 7, also activating factor 10.
   • Common Pathway: Activation of prothrombin to thrombin, converting fibrinogen to fibrin and forming a fibrin mesh to stabilize the clot.

4. Clot Retraction and Repair

   • Platelet Contraction: Actin and myosin in platelets pull edges of the wound together.
   • Platelet-Derived Growth Factor (PDGF): Stimulates smooth muscle and connective tissue repair.
   • Vascular Endothelial Growth Factor (VEGF): Regenerates endothelial cells.

5. Fibrinolysis

   • Purpose: Breakdown of the clot to prevent vessel occlusion.
   • Tissue Plasminogen Activator (tPA): Converts plasminogen to plasmin, which digests fibrin.
   • Diagnostic Use: Elevated D-dimer levels indicate clot formation.

Overview of Drugs Affecting Hemostasis

• Anticoagulants:
  • Heparin: Enhances antithrombin 3.
  • Warfarin: Inhibits vitamin K-dependent factors.
• Antiplatelet Drugs:
  • Clopidogrel: Inhibits ADP.
  • Aspirin: Inhibits thromboxane A2.
• Direct Inhibitors:
  • Dabigatran: Inhibits thrombin.
  • Abciximab: Inhibits glycoprotein 2B3A.

Summary

• Hemostasis is essential for preventing excessive blood loss and ensuring proper wound healing.
• The process involves a complex interaction between vascular constriction, platelet activity, and the coagulation cascade.