Platelet Activation: Adhesion Receptors, Agonists, and Shape Change

Platelet activation is the transition from circulating disc to adhesive, procoagulant effector.

Adhesion (Tethering)

• vWF-GPIb-IX-V: Primary interaction under high shear. vWF binds exposed collagen.
• Collagen-GPVI: Direct collagen binding → strong activation signal.
• Integrins (α2β1, α5β1, α6β1): Bind collagen, fibronectin, laminin.

Activation & Shape Change

Agonists (thrombin, ADP, TxA₂, collagen, epinephrine) → GPCR signaling → ↑ intracellular Ca²⁺ →

• Cytoskeletal reorganization: microtubules coil → pseudopods (spiky form).
• Granule release (α, dense).
• Inside-out activation of GPIIb/IIIa (αIIbβ3) → high-affinity state for fibrinogen/vWF.
• Phosphatidylserine exposure (procoagulant surface).

Aggregation

Fibrinogen bridges activated GPIIb/IIIa on adjacent platelets → aggregates. Stabilized by outside-in signaling, clot retraction.

Clinical Relevance

• Antiplatelet drugs target specific steps: aspirin (COX-1/TxA₂), P2Y₁₂ inhibitors (ADP), GPIIb/IIIa blockers (abciximab, eptifibatide).
• Bleeding disorders: von Willebrand disease (adhesion defect), Glanzmann thrombasthenia (GPIIb/IIIa defect), storage pool disease (granule deficiency).