Initiation of Coagulation Flashcards Preview

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Flashcards in Initiation of Coagulation Deck (15)
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1
Q

What is the domain structure of FVII/FVIIa?

A

Gla domain
2x EGF-like domains
Serine protease domain

2
Q

What is the function of TFPI? How do its domains help it acheive its function?

A

TFPI blocks the active sites of SPs and inhibit
3 domains have different functions:
K2: binds xa and is slow - rate limiting - inhibits FXa (P1 Arg)
K1: binds TF/FVIIa - inhibits TF-FVIIa
K3: binds cofactor Protein S

Gla domain localises the TFPI to the membrane

3
Q

What does the gla domain do?

A

binding to phospholipid surfaces

4
Q

what does the egf domain do?

A

involved in protein-protein interactions

5
Q

What is a serine protease and what is its function?

A

they contain a catalytic triad of his/asp/ser

once activated the serine protease is able to cleave and proteolyse the target substrate

6
Q

What implications does TFPI hold for initiation of coagulation?

A

TFPI threshold must be breached before propogation can occur

suffieient FXa needs to be produced to generate thrombin and become independent of TF/FVIIa

7
Q

What implications does TFPI hold for initiation of coagulation?

A

TFPI threshold must be breached before propagation can occur

sufficient FXa needs to be produced to generate thrombin and become independent of TF/FVIIa

8
Q

How does Protein S enhance the rate of FXa inactivation?

A

It binds TFPI and brings it to the surface, bringing it in closer contact with the TF/FVIIa complex.

9
Q

Where is TFPI made?

A

endothelium

10
Q

What are the other forms of TFPI?

A

TFPI-ß

11
Q

What is the function of TFPI-ß?

A

It binds covalently to the endothelial cell surface protein.

It is able to mediate the “fast” step of coagulation initiation as is already bound to the membrane

12
Q

What are TF microparticles?

A

small cell-derived vesicles from monocytes and other TF expressing cells.
They express P-selectin as do activated platelets
they bear tissue factor in inactive forms

13
Q

Absence of TF?

A

Lethal in-utero

14
Q

Absence of TFPI?

A

Lethal in-utero

15
Q

Absence of FVII and FX?

A

Fatal haemorrhage