Coagulation Pharm Flashcards
(36 cards)
Four phases of coagulation?
Vascular phase, platelet phase, coagulation phase, repair phase
What two parts of the exctracellular matrix are imortant for platelett agg?
VWF and collagen. Yes, VWF is in the matrix.
WHere do VWF and collage bind on the platelet?
VWF- GP1B
Collagen- Gp6
What do ADP and Thromboxane A2 do?
ADP is a platelett recruiting agent
THromboxane A2 is a vasoconstrictor that narrow the vasculature at the site of the wound to bring plateletts close to the wound site.
Fibrinogen binds where on the platelett?
GP2B3A. Fibrinogen and prothrobin are constantly at high concentration in the blood.
What does fibrinogen do?
converted to fibrin and crosslinks clots to stabilize it
What clotting factors are Serine proteases?
Anything with a number except 8,5,and 1.
What are 8,5,and 1?
8 and 5 are cofactors. 1 is a clot structure
What are the key sites of pharm intervention
2 (prothrombin) 10
GEN means?
Inactive form
Pro means?
Inactive form prothrombin is the inactive form of thrombin.
What is factor 13?
A fibrin stabilizing factor, called a transglutamase, basically forms a net around the platelett clot.
Goal of the coagulation phase
Coagulation….so fibrin production
Inhibiting factors are
Protein C, Protein S etc…. these are clot regulators
What lyses a clot?
Plasmin
How is plasmin activated.
Initially binds to Fibrin as plasminoGEN. Then t-PA binds it and converts it to Plasmin.
t-PAI regulates t-PA.
2, 5, 7, 9, 10 are synthesized where and require what?
In the liver, require vitamin K for gamma carboxylation.
5 does not require vitamin k.
Two methods to fight bad clots:
Prevent the formation of it (Heparin and Warfarin…or now aspirin and ticlopidine)
Destroy the clot- Thrombolysis lecture
What the hell does heparin do
Heparin binds anti-thrombin III and increases its affinity for clotting factors 9,10,11,12, and 2 (thrombin). When it binds these, it inactivates these clotting factors.
How many units of heparin do you need to bind ATIII and stabilize it binding to factor 10
16 units
The use of heparin for more than 3-5 days can lead to what?
HIT
HIT is ?
PF4 binds to heparin, ab binds this, this complex binds platelett and activates them.
How does Warfarin work?
Prevents the reduction of Vitamin K by Vit K epoxide reductase. This prevents the gamma carboxylation of 2,7,9,10 pro C and proS
How long does it take for Warfarin to reach its therapeutic effect
36-72 hours, Protein C and S (which are anticoagulants) are inhibited first which leads to a pro-coagulant state dfirst….must take heparin or LMW heparin for first few days.
