Regulation of Coagulation

Question 1

the 3 anticoagulation pathways are:

Answer 1

1- Tissue Factor Pathway Inhibitor Pathway
2- Protein C Pathway
3- Antithrombin-Heparin

Question 2

clotting factors circulate in –
anticoagulation is in –
TF is exposed to — which contains —
when we have vascular injury we will have platelets — and —- cascade

Answer 2

blood
endothelium
blood
clotting factors
adhesion
coagulate cascade

Question 3

Thrombin (FIIa) is generated—
thrombin catalyses — deposition
thrombus formation leads to rapidly – blood loss at the site of injury

Answer 3

rapidly
firbin
attenuates

Question 4

clot formation in vivo:
- exposure to the — proteins —> accumulation of activated — at the site of injury —> — deposition and — formation

Answer 4

sub endothelial
platelets
fibrin
clot

Question 5

Tissue Factor Pathway Inhibitor (TFPI):
-Works by – the — of blood —
- Prevents efficient activation of —
-Blocks interaction between —
-Only works where stimulus (tissue factor exposure) is —
- — response
mechanism of TFPI inhibition:
1- TFPI binds to and inhibits —
2- — stimuli is blocked
3- slow down — of clot formation

Answer 5

stopping
stimulus
blood clotting
activation of coagulation
tissue factor, factor VIIa and factor Xa
low
dampening
FVIIA/FX
clothing
intitation

Question 6

protein c pathway importance:
—- deficiency (no protein C) —> rare, usually –
—– deficiency (50% normal protein C) —> — fold increased risk of —

Answer 6

homozygous
fatal
heterozygous
5-10
venous thrombosis

Question 7

• Excess thrombin binds — on intact — cells w — efficiency
• unbound thrombin is —-
• so basically free throbin is —- :
  it activates —-
  —- amplification (activates FV, FVIII, FXI)
  Cleaves — to form —
  Cell — (via — molecules)

Answer 7

thrombomodulin (TM)
endothelial
high
procoauglation
progaulation serien protease
platelet
feedback
firbongoegn to fibrin
cell signalling via PAR ( these whole steps are how does thrombin generation influence clot structure)

Question 8

• thrombin bound to TM loses its —
• thrombin bound to TM can activate—
  1- thrombin binds —- on EC surface
  2- thrombin:TM complex activates — since when thrombin cleaves to it to release the —- and generate —
• factor Va is cleaved and inactivated by —

Answer 8

progaultion acitvity
protein c
thrombomodiulin
PC
activation peptides and generates APC
APC

Question 9

thrombin ( aka active proteinase) functions as an — on endothelium
1- — binds to TM on endothelial cells
2- — binds to EPCR (endothelial protein C receptor) on endothelial cells
3- — activates protein c
4- activated protein c : —- inhibits thrombin generation at the thrombus edge

Answer 9

anticoagulation
FIIa
protein c
FLLa:TM
protein s

Question 10

Antithrombin functions as a ‘scavenger’ of thrombin:
antithrombin and thrombin aka – proteinase will lead to vessel wall — and the thrombin-antithrombin complex is —

Answer 10

active
heparan sulphate
inactive

Question 11

antithrombin is a —
- Forms a — – complex with all — (XIIa / XIa / Xa / IXa / thrombin)
- However affinity is highest for –
- Most important — of thrombin
- Antithrombin accounts for — of ‘antithrombin’ activity in plasma
- Inactive inhibitor / protease complexes removed by – / –

Answer 11

seprin ( antibiotic)
1:1 irreversible
serine proteases
thrombin
direct inhibitor
70%
spleen/liver

Question 12

— boosts antithrombin function:
- Synthesised as a – in – cells
- — on the endothelium appears to act in a similar manner to heparin
- Accelerates formation of — complexes x 2,000 - x 10,000 fold
- Analogous accelerating role operates in vivo via — intercalated in the surface membrane of endothelial cells.

Answer 12

heparin
proteoglycan in mast cells
heparan sulphate
AT-protease
heparin sulphate

Question 13

— accelerates antithrombin action against thrombin (factor Xa and other coagulation proteinases)
the mode of action:
- alteration of —- when it binds to it
- heparin binds to thrombin approximates AT to — ( so basically template for — )

Answer 13

heparin
conformation active site
substrate
inhibition

Question 14

summary of anticoagulation pathways:
1- TFPI:
- Stop — from starting
- – tissue factor/FVIIa/FXa complex
2- Protein C Pathway
- Detects excess – to trigger anticoagulant pathway
- Breaks down — important for thrombin generation
‘ — feedback loop’
3- Antithrombin-Heparin Pathway
- Binds to — and inactivates and clears from circulation
- Requires — for optimal effect

Answer 14

blood coagulation
inhibits
thrombin
coagulation proteins
-ve
active coagulation proteases
heparans/heparin