Clotting Cascade Flashcards
Hemostasis
Clotting to stop blood flow
What occurs with primary hemostasis?
Platelets aggregate at injury site to form a platelet plug and block the hole
What is formed with primary hemostasis?
Platelet plug at injury site
What occurs with secondary hemostasis?
The platelet plug is further reinforced by a fibrin mesh produced from the coagulation cascade
What is formed with secondary hemostasis?
Fibrin mesh over the platelet plug to reinforce it
What are the 2 pathway options for secondary hemostasis?
Extrinsic pathway
Intrinsic pathway
What activates the extrinsic pathway for secondary hemostasis?
External trauma - blood escapes vascular system
Which pathway for secondary hemostasis is quickest?
Extrinsic
What is the main factor in the extrinsic pathway for secondary hemostasis?
Factor VII
Describe the extrinsic pathway
Factor VII + Tissue factor = VIIa (activated form)
- Then goes to common pathway
What activates the intrinsic pathway for secondary hemostasis?
Trauma inside the vascular system;
platelets, chemicals, collagen
Which pathway for secondary hemostasis is slowest?
Intrinsic
What are the main factors involved in the intrinsic pathway for secondary hemostasis?
Factors XII, XI, IX, VIII
Describe the intrinsic pathway
Prokallikrein activates Factor XII –> XIIa
XIIa activates XI –> XIa
XIa activates IX –> IXa
- Activated Factor VIII and IX then go to common pathway
What is the common pathway?
Where the extrinsic and intrinsic pathways meet and finish the clot production
What factors activate the common pathway for secondary hemostasis?
Factors VII, VIII, IX
For the common pathway, factors VII, VIII, IX activate which factors?
X and V
For the common pathway, factors X and V then activate which factor?
II (thrombin)
Factor II
Thrombin
What does Factor II (thrombin) activate?
- Takes Fibrinogen –> Fibrin
2. Activates Factor XIII
What takes Fibrin –> Cross-linked fibrin mesh?
Factor XIII
What are the major actions of thrombin?
- Creates Fibrin
- Activation of Factor XIII
- Activation of platelets
- Creates more thrombin
Describe the common pathway for secondary hemostasis?
Factor VII (extrinsic) and Factors VIII and IX (intrinsic)
- activate Factors X and V
- X and V activate Factor II
- Factor II takes Fibrinogen to Fibrin
- Factor II activates Factor XIII
- XIII takes Fibrin to Cross-linked Fibrin Mesh!
Is primary or secondary hemostasis quicker?
Primary
Where is Vitamin K activated?
Liver
What enzyme is involved in the first step of Vitamin K activation?
Vitamin K 2,3-epoxide reductase
What is the first step in Vitamin K activation?
Vitamin K 2,3-epoxide is converted (using Vitamin K 2,3-epoxide reductase enzyme) to Vitamin K Quinone
What enzyme is involved in the second step of vitamin K activation?
Vitamin K quinone reductase
What is the second step in Vitamin K activation?
Vitamin K Quinone is converted (using Vitamin K quinone reductase enzyme) to Vitamin K Quinol
What is the active form of Vitamin K?
Vitamin K Quinol
What factors and proteins are activated by Vitamin K Quinol?
Factors II, VII, IX, X
Proteins S and C
Carboxylation of Vitamin K Quinol helps to activate the factors and then converts Vitamin K Quinol to?
Vitamin K 2,3-epoxide
What factors and proteins are activated by Vitamin K Quinol?
Factors II, VII, IX, X
Proteins S and C
What is the mechanism of action of anticoagulants?
Vitamin K INHIBITION
What are the 2 types of anticoagulants?
- Hydroxycoumarins
2. Indanediones
What is the main hydroxycoumarin type of anticoagulant?
Warfarin
Main goal of Warfarin?
PREVENT blood clots from forming
- lengthens time it takes for a clot to form
How does Warfarin try and prevent blood clots from forming?
By DECREASING the activity of Vitamin K 2,3-epoxide reductase enzyme
What enzyme does Warfarin try to inhibit?
Vitamin K 2,3-epoxide reductase
Hemophilia A
Factor VIII deficiency
Where in secondary hemostasis, would a Factor VIII deficiency (Hemophilia A) be located?
It is needed at the end of the intrinsic pathway (along with Factor IX) to activate the common pathway and finish clot production
How does one get Hemophilia A?
Usually hereditary but can be caused by spontaneous mutations
With Hemophilia A, what type of bleed would you have the most trouble clotting?
Intrinsic - Trauma inside the vascular system
