Clotting Cascade Flashcards
When a pt is first given Warfarin, why is the full effect not seen for about 48 hours?
Because the previously activated factors in the blood must decline and re-synthesis must begin before warfarin will interfere
What is the half life of factor II?
60 hours
What is the half life of factor IX?
24 hours
What is the half life for factor X?
40-60 hours
What are the two pathways for secondary hemostasis?
Intrinsic and extrinsic
What is the extrinsic pathway?
Activated by external trauma
Blood escapes vascular system
Quicker than the intrinsic pathway
Involves factor VII
What is the intrinsic pathway?
Activated by trauma inside the vascular system
Activated by platelets, exposed endothelium, chemicals or collagen
Slower than the extrinsic pathway
Involves factor XII, XI, IX and VIII
What is the common pathway?
Pathways meet and finish the pathway of clot production
Involves factors I, II, V and X
What is primary hemostasis?
Platelets in the blood aggregate at the injury site and form a platelet plug to block the hole
What is secondary hemostasis?
Platelet plug is further reinforced by a fibrin mesh produced through proteolytic coagulation cascade
What is the key difference between primary and secondary hemostasis?
Primary hemostasis makes a weak platelet plug at the injury site while secondary hemostasis makes it strong by generating a fibrin mesh on it
What are the major actions of thrombin?
Prothrombin —> thrombin Activation of platelets Factor XIII -> XIIIa cross linked fibrin Fibrinogen —> fibrin Factor V -> Va Factor VIII —> VIIIa
What are the two types of anticoagulants?
Hydroxycoumarins (ex. Warfarin)
Indanediones
What is the mechanism of action for anticoagulants?
Vitamin K inhibition
What is the first step for the activation of vitamin K?
Vitamin K 2,3 epoxide reductase uses reduced NADH as a cofactor to convert vitamin K 2,3 epoxide —> quinone form
What is the second step for the activation of vitamin K?
Quinone reductase reduces the quinone form of vitamin K —> the active vitamin K quinol form
What is the role of gamma-glutamyl carboxylation in the vitamin K cycle?
Converts active vitamin K quinol back into the inactive vitamin K 2,3 epoxide
Also converts inactive factors II, VII, IX, X, proteins S and C into their active forms
What does warfarin target?
Vitamin K dependent epoxide reductase
Decreases its activity which increases the time it takes for a clot to form
What is vitamin K epoxide reductase?
An enzyme that reduces vitamin K after it has been oxidized in the carboxylation of glutamic acid residues in blood coagulation enzymes II, VII, IX and X as well as proteins S and C
What is the mechanism of action for warfarin?
Blockade of gamma-carboxylation of several glutamate residues in prothrombin (II) and factors VII, IX and X as well as endogenous anticoagulant proteins C and S
What enzymes are involved in the metabolism of warfarin?
CYP2C9 makes S-warfarin
CYP1A2, 3A4, 2C19 make R warfarin
Peak plasma concentrations of warfarin occur when?
3 hours after drug administration
Describe S warfarin
More highly bound to albumin than R warfarin
Less protein bound than R warfarin
5x more potent as a blood anticoagulant than R warfarin
Drugs that alter the level of free warfarin (e.g. by competing or binding to albumin or inhibiting warfarin metabolism) may influence what?
The anticoagulant effect
