3.2: Platelet Activation And Microplatelets Flashcards
Sequence of events of adhesion:
- Collagen
- Vwf
- GP lb/IX/V
- ADAMTS-13
- GP VI
- TXA2 and ADP
- TPa and TPb
- P2Y1 and P2Y12
- A2B1
Sequence of events of aggregation:
- Tissue factor
- Thrombin
- PAR1 and PAR4
- COAT platelets
- TXA2 and ADP
- GP IIb/IIIa receptor
- P-selectin
- Phosphatidylserine
The combination that triggers secondary hemostasis
- Polar phospholipid exposure on activated platelets
- Platelet fragmentation with cellular microparticle release
- Secretion of the platelet’s alpha grange and dense granule contents
Sequence of events of secretion
- STRs
- GP VI
- Intermediate filaments
- Actin microfilament
- Alpha granules
- Lysosomes
- Dense granules
- Phosphatidylserine
Is disrupted and exposed during blood vessel injury
Collagen
Is released when endothelial cells become
damaged, then adheres to the site of injury;
Under shear stress, it becomes thread-like
as it unrolls and exposes sites that weakly
bind the GPIbα portion of the GP Ib/IX/V
receptor
vWF
Platelet membrane receptor in adhesion
GP Ib/IX/V
A liver-secreted plasma enzyme which
digests larger vWF multimers into smaller, less biologically active forms; Localizes the
platelet-vWF interaction
ADAMTS-13
Collagen binding to ______ triggers internal platelet activation pathways, releasing TXA2 and ADP, an outside-in reaction
GP VI
Are agonists that bind to the receptors TPα
and TPβ and P2Y1 and P2Y12 ,
respectively, for ADP that triggers an
inside-out reaction that raises the affinity of
integrin α2β1 for collagen
TXA2 and
ADP
STRs of adhesion
TPα and TPβ
P2Y1 and P2Y12
Increased affinity for collagen
α2β1
Blood vessel injury exposes these and are expressed on subendothelial smooth muscle cells and fibroblasts; Triggers the production of thrombin
Tissue factor
Cleaves platelet PAR1 and PAR4
Thrombin
STRs of aggregation
PAR1 and PAR4
“collagen and thrombin activated” platelets; Generated by the activation of thrombin formation
COAT platelet
Are platelet activators that is secreted from the platelet granules to the microenvironment, where they activate neighboring platelets through their respective receptors and trigger inside-out activation of integrin αIIbβ3 (GP IIb/IIIa receptor)
TXA2 and ADP
Binds to the RGD sequences of fibrinogen and vWF; Supports platelet-to-platelet binding
GP IIb/IIIa receptor
Moves from the alpha granule membrane to the surface membrane to promote binding of platelets with leukocytes
P-selectin
The more polar phospholipid molecules flip to the outer layer; Platelets change in shape from discoid to round and extend pseudopods
Phosphatidylserine
Triggers actin microfilament contraction
STRs
GP VI
Also contract, moving the circumferential microtubules inward compressing the granules
Intermediate filaments
Contracts due to the outside-in activation
Actin microfilament
Flows through SCCS with the lysosomes; Are large molecule
coagulation proteins that participate in secondary hemostasis; Its contents (fibrinogen, factors V and VIII, and vWF) are secreted and increase the localized concentrations of the essential coagulation proteins, further supporting the action of tense and prothrombinase
Alpha granules
Flows through the SCCS with alpha granules
Lysosomes
Are small vasoconstrictors and platelets agonists that amplify primary hemostasis
Dense granules
Is a polar phospholipid on which the factor IX/VIII (tenase) and X/V (prothrombinase) complexes assemble; Is supported by the ionic calcium secreted by the dense granules; OIs presented on the platelet membrane surface providing a localized cellular milieu that supports coagulation
Phosphatidylserine
Are formed after exposure of platelets to strong agonists or shear stress
Platelet Microparticles
Are membrane-derived vesicles that form in response to an activating stimulus that increases the platelet intracellular concentration of calcium
Platelet Microparticles
Control cellular activation for all cells at the inner membrane surface
G-proteins
αβγ heterotrimers that bind guanosine diphosphate
(GDP) when inactive
G-PROTEINS
of the heterotrimer briefly dissociates,
exerts enzymatic guanosine triphosphate activity and
hydrolyzes the bound GTP to GDP, releasing a
phosphate radical
Gα portion
EICOSANOID SYNTHESIS Alternatively called the
prostaglandin, cyclooxygenase, or thromboxane pathway
One of the two essential platelet activation pathways
triggered by G-proteins in platelets
EICOSANOID SYNTHESIS
An inner phospholipid whose number 2 carbon binds numerous types of unsaturated fatty acids, but especially 5, 8, 11, 14-eicosanoid acid (arachidonic acid)
Phosphatidylinositol
a membrane enzyme that cleaves the ester bond connecting the number 2 carbon of the triglyceride backbone with arachidonic acid
Phospholipase A2
is released to the cytoplasm as it is cleaved
Arachidonic acid
Converts arachidonic acid to prostaglandin G2 and prostaglandin H2
Cyclooxygenase
Acts on prostaglandin H2 to produce TXA2
Thromboxane A2
Binds membrane receptors TPα and TPβ (inhibits adenylate cyclase activity and reducing cAMP concentrations, which mobilizes ionic calcium from the DTS)
TXA2
Is incorporated in place of the thromboxane synthetase
Prostacyclin synthetase
The eicosanoid pathway end point for the endothelial cells
Prostaglandin I2 or prostacyclin
Binds to the IP receptor activating the IP3-DAG pathway
Prostaglandin I2 or prostacyclin
Leads to the acceleration of adenylate cyclase, an increase in cAMP, and a sequestration of ionic calcium to the DTS
Prostaglandin I2 or prostacyclin
Is the second G-protein-dependent platelet activation
pathway
IP3-DAG ACTIVATION PATHWAY
Phospholipase C cleaves PIP2 to form
IP3 and DAG
are second messengers for intracellular activation
IP3 and DAG
Promotes release of ionic calcium from the DTS (triggers actin microfilament contraction)
IP3
Also activates phospholipase A2
IP3
Activates phosphokinase C (triggers phosphorylation of the protein pleckstrin)
DAG
