Thrombogenesis

Overview

• Always a balance between pro-aggregation and anti-aggregation forces
• Formation of a platelet plug occurs in four main stages
  • Adhesion 
    • platelet Gp1b receptor binding to exposed subendothelial collagen
      • mediated by vWF
  • Aggregation
    • vasoconstriction results in decreased blood flow
      • mediated by activated platelets which synthesize TxA₂ by cyclooxygenase I enzymes
        • COXI inhibited by aspirin which results in ↓ aggregation
    • PGI₂ and NO released by endothelial cells are natural aggregation inhibitors by vasodilating vessels
  • Swelling
    • inter-platelet binding via fibrinogen cross links to GpIIb/IIIa receptors on platelet membrane
      • GpIIb/IIIa inserted on membrane by binding of ADP to platelet ADP receptors
    • once this step happens the bleeding stops and is the end of the “bleeding time” test
      • although clot has formed, it is unstable and easily disrupted
  • Maturation
    • fibrinogen is converted to fibrin with cross-linking to strengthen plug
    • Ca²⁺ also strengthens platelet plug