Lecture 5: Hemostasis Review Flashcards
What is the goal of hemostasis?
Keeping blood within a damaged blood vessel and is the first stage of wound healing.
What is hemostasis the balance between?
Procoagulant and anticoagulant factors.
What are the 4 phases of hemostasis?
- Initiation and formation of the platelet plug.
- Propagation of the clotting process by the coagulation cascade.
- Termination of clotting by antithrombotic control mechanisms.
- Removal of the clot by fibrinolysis.
What are the 3 main components in hemostasis?
Blood proteins (factors)
Platelets
Vessel wall (factors)
How long do endogenous platelets circulate?
~10 days
How long does it take to make a new batch of platelets?
3-5 days in the bone marrow.
How many platelets get pooled in the spleen?
1/3 of all platelets.
What is normal platelet count?
150k-450k
What are the dense granules in a platelet?
Serotonin
ADP
Ca
ATP
What are the alpha granules in platelets?
Platelet derived growth factor
Transforming growth factor beta
Fibrinogen
Von Willebrand factor
Platelet factor 4
Factor V
How do platelets promote clotting?
At the site of an active bleed, platelets will bind to exposed collagen to form the primary plug.
After forming the initial plug, addl plts recruited to expand and propagate the clot.
What happens once a platelet plug is made?
Clotting cascade begins with fibrin deposition
What hormone activates other platelets?
Thromboxane
Where is von willebrand factor synthesized and stored?
Endothelial cells
Platelets
What is the goal and unique characteristic of von willebrand factor?
Binds to other proteins
It is not an enzyme, so it does not need to be catalyzed.
What are the 3 functions of von willebrand factor?
- Binds to endothelium and promotes platelet adhesion to sites of vessel injury.
- Plasma carrier for Factor 8, preventing its degradation.
- Binds to collagen when exposed.
What releases factor 8 from vWF?
Thrombin
What is a deficiency in von willebrand factor linked to?
A factor 8 deficiency, aka hemophilia.
What are the main principles of secondary hemostasis?
Clotting factors circulate inactive
Activate each other (cascade effect)
What activates the extrinsic pathway?
Tissue factor OUTSIDE of the blood.
What activates the intrinsic pathway?
Factors found IN the blood.
What are the steps of the extrinsic cascade?
7 activates 10.
What are the steps of the intrinsic cascade?
12 => 11 => 9 => 8
What are the steps of the common pathway?
10 => 5 => 2 => 1
What are the 3 essential steps of blood coagulation?
- Complex of substances called prothrombin activator is formed.
- Prothrombin activator converts prothrombin to thrombin.
- Thrombin converts fibrinogen to fibrin.
What are the two ways prothrombin factor is formed?
Extrinsic and intrinsic pathway.
What coagulation factors require Vit K?
2, 7, 9, 10, C, S
What is the only factor not made by the liver?
3
When does Vit K go down?
Fat malabsorption/malnutrition
ABX therapy (esp. cephalosporins)
IN the newborn
What drug is a vit K antagonist?
Warfarin/coumadin
What triggers the extrinsic pathway?
Trauma to vascular wall or tissues.
What are the 3 steps of the extrinsic pathway?
- Release of tissue thromboplastin from traumatized tissue.
- Activation of Factor 7
- Activation of Factor 10, which forms the prothrombin activator.
What triggers the intrinsic pathway?
Trauma to the blood itself OR exposure of blood to collagen.
What are the 5 steps of the intrinsic pathway?
- Exposure of collagen causes activation of Factor 12.
- Factor 11 is activated.
- Factor 9 is activated in presence of Ca.
- Factor 11a, 8a and Ca form a complex to activate factor 10.
- Factor 10 activation forms prothrombin activator.
Where is prothrombin continuously produced?
Liver
What is required for prothrombin activation?
Vit K
How does a fibrin network form?
Fibrinogen is converted to fibrin by thrombin.
Fibrin polymerizes with other fibrin molecules to form a retinaculum.
What are the 3 roles of fibrinogen/factor 1?
- Transforms the unstable platelet plug into a stable, permanent plug.
- Induces platelet aggregation
- Starts fibrinolysis process.
What are the AC plasma proteins?
Protein C and S, antithrombin (3), and tissue factor pathway inhibitor.
What do protein C and S do?
Upon activation, they have a direct effect on the conversion of prothrombin to thrombin.
Active protein C and S complex inhibits 5 and 8.
What are protein C and S dependent on?
Vit K
What does anti-thrombin 3 do?
Inactivates thrombin, 9a, 10a, 11a, and 12a
What accelerates anti-thrombin?
Heparin. Boosts inhibition of the factors 1000x.
What does t-PA do?
Activates fibrinolysis via activation of plasminogen.
What does a D-dimer measure?
The degradation products of plasmin.
What best describes the function of activated protein C complex?
Inhibits factor 5a and 8a.
What best describes the function of tPA?
Conversion of plasminogen to plasmin.
