Coagulation Flashcards
What is the culminative event of coagulation?
The generation of thrombin
What is Thrombin’s function?
Turns soluble fibrinogen to Fibrin
What is the function of fibrin?
enmeshes the platelet aggregates at the sites of vascular injury and converts the unstable primary plug to firm definitive and stable haemostatic plug
Of all the enzymes of coagulation which is not a serine protease?
Factor VIII (8)
What are the three enzyme complexes that thrombin generation is dependent on?
1.Extrinsic case (VIIa, TF, PL, Ca2+)
2.Intrinsic case (IXa, VIIIa, PL, Ca2+)
These 2 pathways both generate FXa and the prothrombinase complex (Xa,Va,PL,Ca2+) generating thrombin
How does the generation of thrombin occur after tissue injury?
In two waves.
What happens during the initial wave?
Small amount generated which prepares the coag cascade for the second larger burst.
How does initiation occur?
Occurs by the interaction of membrane bound (TF) which is exposed and activated by an enzyme protein dislphide isomerase after vascular injury, with plasma factor VIIa.
What is TF?
The sole initiator of thrombin generation and fibrin formation. It is expressed on fibroblasts of the adventitia and small muscle of the vessel wall, and on non vascular cells.
What does Factor VIIa activate?
Activates both both Factor IX and Factor X
What inhibits the extrinsic pathway (extrinsic case)?
Tissue factor pathway inhibitor.
What does TFPI form?
A complex with VIIa, TF and Xa
What does this inactivation of extrinsic pathway lead to?
Dependence of thrombin generation on the intrinsic pathway.
What happens to the small amounts of Thrombin generated by the Extrinsic pathway?
It activates Factors VII and V to VIIIa and Va
How is the prothrombinase complex (Xa + Va) formed?
Xa is generated by IXa and VIIIa (Intrinsic Xase) in the presence of calcium Ca2+, which then combines with Va PL and Ca2+.
What does generation of prothrombinase yeild?
THROMBIN
What is the role of Factor XI?
- Does not seem to have a role in physiological initiation of coag.
- Appears to have a role in activation of Factor IX.
What is the role of Thrombin? How does it work?
Hydrolyzes fibrinogen releasing Fibrinipeptides A and B to form Fibrin monomers.
What Happens to The Fibrin monomers?
Bound spontaneously by hydrogen bonding to form loose insoluble fibrin polymer.
How is Factor XIII activated?
By Thrombin + Ca2+
What is a function of Xllla?
Stabilizes the fibrin polymers with formation of covalent cross links
Describe Fibrinogen
Heterodimer of 3 dissimilar sub units Alpha, Beta, and Gamma.
Which factors are dependent upon Vitamin K?
2, 7, 9, 10
Why is vitamin K important for these factors?
Carboxylates some terminal glutamic acid residues on those molecules.
Which 2* factors are not protease enzymes?
V and VIII
What 3 molecules produced by Endothelial cells have a inhibitory effect on platelets?
NO, CD39, and Prostacyclin
What 2 molecules released by platelets also have vasocontricive activity?
TXA2 and Fibrinopeptides.
What facilitates platelet adherence to exposed connective tissue?
GPIa and GPIb mediated via VWF