Flashcards in Antiplatelet, anticoagulant and thrombolytic drugs and the mechanism of clotting Deck (87)
What is the starting process in almost all clot formations?
It begins with a local event that causes damage to the wall
What does the damage to the endothelial wall expose?
Tissue factor and collagen
What does the exposed collagen bind to?
What does collagen bound vWF act as ?
a cross bridge because it will also allow the platelets to bind to it through the glycoprotein Ib (GP Ib) receptor on the platelet surface.
What is the receptor on the platelet that binds to vWF – collagen complex?
How is the binding of the platelet to the blood vessel further stabalised ?
Interactions are formed by Integrin A2 B1 and glycoprotein VI on the platelet binding to collagen
Which two things initiate platelet activation?
Glycoprotein VI anchoring and thrombin
What does the platelet do in response to activation?
a. 1.changes shape (extends pseudopodia) which then gives aggregated platelets
b. 2.The platelet also starts to synthesise thromboxane A2 (TA2,)
How is TA2 formed?
It is formed from arachidonic acid through the enzyme COX1
TA2 acts in both an ----- and ____ manner.
TA2 acts in both an autocrine and paracrine manner.
what is the receptor called that TA2 binds to?
what does the binding of TA2 to GPCR TXA2 do?
causes the release of
i) 5-hydroxytryptamine (aka seratonin) and ADP
ii) vWF and factor V
what do the dense granules release?
5- hydroxytryptamine (5-HT) (aka seratonin) and ADP
what do the alpha granules release?
vWF and factor V
why do the blood vessels vasoconstrict?
because TXA2 acts directly on smooth muscle and also 5-HT binds to receptors on the surface causing vasoconstriction
what does ADP bind to ?
platelet GPCR P2Y12 receptors
what does the binding of ADP do? 3 things
i) activation of further platelets
ii) Increases the expression of glycoprotein IIb and IIIa receptors
iii) causes exposure of acidic phospholipids on the platelet surface - this facilitates the formation of the clot
what do GP IIb and IIIa do?
they are binding points for fibrinogen on the platelet surface
what is the KEY event in the coagulation cascade?
the production of protease thrombin (factor IIa) that cleaves fibrinogen to fibrin to form a solid clot
what is coagulation?
the conversion of the soft plug to form a solid clot which assists in the healing process.
1. what does the tissue injury expose ?
matrix tissue factor (thromboplastin)
2.which factor binds to TF?
VII - this complex TF:VIIa is now active
3.what does the TF:VIIa complex do?
activates factor X (x- Xa)
4. what does the activates Xa bind to ?
5. what does the Complex VaXa do?
converts prothrombin to thrombin - this is the key player
6. what is the first thing that thrombin does?
activates further platelets - in doing so it causes the release of factor V from alpha granules in the platelet cytoplasm - when these factors reach the surface they become active
7. what does thrombin do to TF:VII (8) ?
It liberates factor VIII which then becomes active
8.what does thrombin do to XI?
converts it to XIa
9.how is IX activated?
by wither TF- VIIa or XIa