Clotting Cascade Flashcards
What will activate the extrinsic pathway in the clotting cascade?
Via external trauma - blood escape from vasc. System
Is the extrinsic or intrinsic pathway quicker in the clotting cascade?
Extrinsic = quicker
What is the extrinsic pathway?
3 (tissue factor) —> 7 —> 10
10–> 2 (thrombin) —> 1 (fibrin)
What will thrombin go back and activate in the extrinsic pathway?
Will feedback to activate:
5, 7, 8, 11
What stimulates the production of anti-thrombin? What will it impede?
Thrombin stimulates it
Impedes thrombin and factor 10
What is the intrinsic pathway?
12 —> 11 —> (9+8) tenase complex —> (10+5) prothrombinase complex
—> 2a (active thrombin)
How is fibrin cross linked?
Via factor 13
What is primary hemostasis?
Platelets in blood aggregate at injury site and form a platelet plug to block hole
What is secondary hemostasis?
Platelet plug is further reinforced by a fibrin mesh produced thru proteolytic coagulation cascade
What is the KEY difference b/w primary and secondary hemostasis?
Primary = weaker plug
Secondary - strong plug bc fibrin mesh is on it
Is primary or secondary hemostasis longer?
Secondary
What is thrombin, generally?
PROTEASE that cuts proteins
What proteins will thrombin act on?
Fibrinogen
Factor 8
Factor 5
Factor 13
Will activate platelets
Prothrombin
What form do we ingest Vit. K in?
How do we make it active?
Ingest in quinone form
Activate via quinol form in liver
What is the mechanism for activation of Vitamin K?
Step 1:
Vit. K 2,3, epoxide reductase + NADH —> quinone form
Step 2:
Quinone reductase —> active v. K. Quinol from
What are 2 examples of anticoagulants?
Hydroxycoumarins
Indanediones
What is an example of hydroxycoumarins?
Warfarin
How do blood clots form?
So how does warfarin prevent the formation of blood clots?
Thru a series of Vit. K dependent rxns in liver
Warfarin decreases activity of Vit. K. Epoxide reductase
Which enantiomer of Warfarin is more potent? (R or S)
S-warfarin - 2-5x more potent
When is warfarin pharmacologically active?
When it is FREE
Why is Vit. K. Important in the clotting cascade?
Cofactors in synthesizing factors 2, 7, 9, 10, protein s and protein c
What does protein c do?
Inactivates t-Pa = no active plasmin
Which factor has the longest half life?
Factor 2
What are the roles of Protein S and C?
Anti-coagulation action by maintaining permeability of blood vessel walls
