Medicine & USMLE

Platelet Plug Formation

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Platelet Disorders
  1. Platelet Plug Formation
  2. Von Willebrand Disease
  3. Bernard-Soulier Syndrome
  4. Glanzmann Thrombasthenia
  5. Immune Thrombocytopenic Purpura (ITP)
  6. Thrombotic Thrombocytopenic Purpura (TTP)
  7. Hemolytic Uremic Syndrome (HUS)
  8. Disseminated Intravascular Coagulation (DIC)

Summary

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Key Points

  • Platelet Plug Formation
    • Also known as primary hemostasis
      • First step of blood clot formation
      • Coagulation cascade is known as secondary hemostasis
    • Injury exposes collagen (subendothelial) and matrix
      • Transient vasoconstriction
        • Via neural stimulation reflex and endothelin (released by damaged endothelial cells)
        • Works to slow blood flow, increasing time for vWF and platelets to bind
      • vWF binds to exposed collagen
        • vWF from Weibel-Palade bodies in endothelial cells and alpha-granules of platelets
    • Platelet adhere to vWF via GpIb to damaged vessel wall
      • Platelet activates and degranulates after binding to release:
        • ADP
          • Stimulates activation of nearby platelets (see below)
        • Thromboxane A2 (TXA2)
          • Also stimulates platelet activation
          • Aspirin blocks TXA2 by preventing its synthesis by COX
        • Calcium (Ca2+)
          • Stimulates coagulation cascade (secondary hemostasis) and improves stability of platelet plug
        • Von Willebrand Factor (vWF)
          • Found in alpha-granules of platelets, contributes to even more adhesion
      • Ristocetin activates vWF to bind GpIb
        • Used in ristocetin cofactor assay to diagnose vWD (deficiency of vWF) and Bernard-Soulier syndrome (deficiency of GpIb)
    • Nearby platelets activate
      • ADP binding to ADP-receptor (P2Y12 receptor) induces GpIIb/IIIa expression on surface
        • Clopidogrel, prasugrel, and ticlopidine block ADP-receptor to reduce GPIIb/IIIa expression
        • Abciximab, eptifibatide, and tirofiban block GpIIb/IIIa directly
      • Activated platelets also undergo conformational change
        • Spread out in shape to become wider, allowing more blockage of flow and more surface for adhesion
    • Platelets aggregate into a plug
      • Fibrinogen links platelets together via GpIIb/IIIa
        • This is a temporary platelet plug, unstable and easily dislodged
        • Requires fibrinogen to be converted into fibrin to stabilize blood clot (via secondary hemostasis)
        • Fibrinogen is derived from dense granules of platelets
      • Maintenance of platelet plug is a balance between
        • Pro-aggregation factors
          • TXA2
            • released by platelets, stimulates activation
          • Decreased blood flow
            • Slowing blood flow allows more platelets to interact with the surface
          • Increased platelet aggregation
            • Blocking vessel lumen to slow blood flow
          • Platelet-activating factor (PAF)
        • Anti-aggregation factors
          • PGI2 and NO (released by endothelial cells)
            • Work to vasodilate blood vessels, thereby increasing blood flow and decreasing platelet adhesion
          • Increased blood flow
          • Decreased platelet aggregation
    • Monitoring
      • Bleeding time (BT)
        • Measures time to platelet plug