Primary Hemostasis

Platelet Zones {Components & Functions}

1. Peripheral zone: plasma membrane + glycocalyx (outer surface coat)+ Open Canalicular System (secretion pathway, extra surface area when platelets change shape)

   • Adhesion, platelet activation, receptor interactions

2. Sol-Gel zone: cytoskeleton + microtubular system (microtubular & microfilament)

   • Shape change, clot contraction & retraction

3. Organelle zone: mitochondria + alpha granules + dense granules + lysosomes + dense tubular system (store & release calcium)

   • Stores & releases substances

Glycocalyx

Exterior surface of platelets that are rich in GP, enable adhesion & aggregation via receptors binding to fibronectin, vitronectin, collagen, vWF

Fibronectin

• Glycoproteins that et platelets adheres to extracellular matrix

• Not the same as fibrinogen

Vitronectin

Glycoprotein that regulates complement system and adhesion to extracellular matrix

Open Canalicular System (OCS)

Channel membrane extending deep into platelets, pathway for granule secretion, plasma procoagulants absorption, and calcium regulation

Microtubules {Composition, Function}

• Composed of tubulin (protein subunits)

• Encased the platelets into discoid shape when platelets at rest

• Contract organelles toward center when platelets are activated, then disappear & reappear in pseudopods to regulate platelate response

Microfilaments {Composition, Function}

• Composed of thrombosthenin (actin & myosin)

• Shape change (unorganized gelatinous state → organized) for contraction

Dense Granules {Amount, Released Contents, Function}

• 2-10 per platelet

• Stored & Released

  • ADP

  • Serotonin

  • Calcium (few)

Lysosomes

Contain digestive enzyme that contribute to breakdown of plug & exposed material during injury

Mitochondria & Glycogen {Amount, Function}

• 10-60 mitochondria per platelet

• Produce ATP using glycogen as reactants

Dense Tubular System (DTS)

• Site of prostaglandin & TXA2 synthesis

GP Ib/IX/V {Composition, Function}

Known as adhesion receptor. Main ligand is vWF for the platelets to attach to the vessel. Composed of:

• Two GP-Ib-alpha: binds vWf

• Two GP-Ib-beta: anchor receptor complex to the cytoskeleton

• Two GP-IX & one GP-V: stabilized the receptor complex

GP-IIb/IIIa {Function}

• Inside-out signal: platelets become active and receptor bind to fibrinogen

• Outside-in signal: signals send back after binding → platelets spread/retract that strengthen the clot

Platelet Shape Change {Mechanisms, Results}

1. Procoagulants (ADP, collagen, thrombin, TXA₂) trigger release of cytosolic calcium (calcium in cytoplasm) in dense tubular system

2. Increased in calcium → lose discoid shape (microtubule rearranged)

3. Microfilaments organized to strengthen the plug in later stages

4. Microtubule contract to form sphere-pseudopod shape (organelles centralize)

5. Negatively charged phospholipid surface PF3 is exposed for coagulation cascade to occur and produce fibrin

Alpha Granules {Amount,Released Contents, Function}

• 20-200 per platelet

• Stored & release proteins involved in adhesion, coagulation, repair

  • vWF

  • Fibrinogen Platelet Factor-4 (PF4): bind heparin to neutralize it → reduced anticoagulant

  • Platelet-derived growth factor (PDGF): heal & repair vessels

Platelet Aggregation {Classification, Requirements}

Primary aggregation:

• Reversible

• platelet-platelet binding that form initial plug

Secondary aggregation:

• Non-reversible

• Granule contents (ADP, serotonin, calcium) are released

• Viscous metamorphosis (transformation of initial platelet plug into definitive plug)

• Lysosomal release contributes to plug consolidation & eventual dissolution

Requirements

• Activated GP-IIb/IIIa receptors

• Fibrinogen

• Calcium

• ATP (power the receptors)

Lumiaggregometry {Assessment, Clinical Value}

• Assess platelet aggregation & ATP secretion through optical density. Percent transmission rises after platelets aggregate

• Diagnose dense granule storage pool & drug effects on platelet aggregation

Aspirin {Mechanism}

• Irreversibly blocks COX-1 in platelets → decreased TXA2 → decreased platelet aggregation

• Platelets lacked nucleus to produce COX