Mechanisms of Clotting activation

Question 1

Where is tissue factor localised?

Answer 1

Plasma membrane of adventitial fibroblasts, skin keratinocytes & epithelial cells

Question 2

What does TF triggering cause?

Answer 2

Localized activation of coagulation at site of vascular adamge

Question 3

What is TF a cofactor of?

Answer 3

Factor VII

Question 4

What does binding of VII to TF cause?

Answer 4

Formation of VIIa which activates IX and X by proteolysis

Question 5

Which 4 factors have Gla domains?

Answer 5

VII
IX
X
II

Question 6

Which 2 factors have the C2 domains?

Answer 6

V
VIII

Question 7

What are gla domains needed for?

Answer 7

Membrane attachment

Question 8

How is amplification of thrombin generated?

Answer 8

Initial thrombin activates XI, VIII, V and platelets

Question 9

What 3 things are essential for clot formation?

Answer 9

-vely charged phospholipids on platelets
active VIII
active V

Question 10

What is the prothrombinase complex composed of?

Answer 10

prothrombin (II)
Xa
Va

Question 11

What do the prothrombinase complex assemble on?

Answer 11

-vely charged membrane surface containing phosphatidylcholine & phosphatidylserine (PCPS)

Question 12

Which factor can float around?

Answer 12

IIa (thrombin) - more power

Question 13

Where is factor VIII synthesized?

Answer 13

Liver and endothelial cells

Question 14

When is VIII stabilized in plasma?

Answer 14

By binding to vWF

Question 15

How does VWF affect VIII?

Answer 15

Inhibits binding to PL and platelets
Active VIIIa is released from vWF

Question 16

Where is factor V synthesized?

Answer 16

liver

Question 17

What do c1/2 domains mediate?

Answer 17

Attachment of factors VIII and V to plasma membrane

Question 18

What are factors VIII/V activated by?

Answer 18

thrombin

Question 19

What are factors VIII/V inactivated by?

Answer 19

APC

Question 20

What is ‘contact’ activation?

Answer 20

When foreign surfaces activate the clotting cascade

Question 21

What is the intrinsic pathway?

Answer 21

Something in blood that causes clotting without the need for TF

Question 22

Which factor can kick off clotting cascade without TF?

Answer 22

XII

Question 23

What does FXII activate?

Answer 23

Prekallikrein -> kallikrein

Question 24

What does kallikrein release?

Answer 24

Bradykinin from kininogen

Question 25

What is bradykinin?

Answer 25

Vasoactive molecule that triggers NO production & plays a role in inflammation