Mechanisms of Clotting activation Flashcards
Where is tissue factor localised?
Plasma membrane of adventitial fibroblasts, skin keratinocytes & epithelial cells
What does TF triggering cause?
Localized activation of coagulation at site of vascular adamge
What is TF a cofactor of?
Factor VII
What does binding of VII to TF cause?
Formation of VIIa which activates IX and X by proteolysis
Which 4 factors have Gla domains?
VII
IX
X
II
Which 2 factors have the C2 domains?
V
VIII
What are gla domains needed for?
Membrane attachment
How is amplification of thrombin generated?
Initial thrombin activates XI, VIII, V and platelets
What 3 things are essential for clot formation?
-vely charged phospholipids on platelets
active VIII
active V
What is the prothrombinase complex composed of?
prothrombin (II)
Xa
Va
What do the prothrombinase complex assemble on?
-vely charged membrane surface containing phosphatidylcholine & phosphatidylserine (PCPS)
Which factor can float around?
IIa (thrombin) - more power
Where is factor VIII synthesized?
Liver and endothelial cells
When is VIII stabilized in plasma?
By binding to vWF
How does VWF affect VIII?
Inhibits binding to PL and platelets
Active VIIIa is released from vWF
Where is factor V synthesized?
liver
What do c1/2 domains mediate?
Attachment of factors VIII and V to plasma membrane
What are factors VIII/V activated by?
thrombin
What are factors VIII/V inactivated by?
APC
What is ‘contact’ activation?
When foreign surfaces activate the clotting cascade
What is the intrinsic pathway?
Something in blood that causes clotting without the need for TF
Which factor can kick off clotting cascade without TF?
XII
What does FXII activate?
Prekallikrein -> kallikrein
What does kallikrein release?
Bradykinin from kininogen
What is bradykinin?
Vasoactive molecule that triggers NO production & plays a role in inflammation
