Flashcards in Coag Deck (108):
What is hemostasis?
The cessation of bleeding from a cut or severed vessel
What are the five hemostasis systems?
Deficiencies in any of the clotting systems can lead to what?
What is vasoconstriction controlled by?
Local factors by the tissues
What is the first response to a cut?
Local factors released to vasoconstrict
Activated platelets at the side of injury release what? What do these do?
What does the coagulation system produce that induces blood vessel endothelial cells to produce endothelin 1?
What is the function of endothelin 1?
Platelets adhere to the side of a vessel through what? What does this cause?
Surface glycoproteins receptors
Causes change in shape of platelets, and activates further platelets
What is in the ECM that is exposed during an injury, and causes initial platelet binding? What is the receptor on the platelet?
von Willebrand factor (vWf)
Receptor = GP1-b-alpha
What is Willebrand factor disease?
loss of vWf, leading to increased bleeding
After initial platelet tethering, what protein binds collagen in the ECM, that begins to activate platlets?
Platelet glycoprotein VI
What is the role of fibrinogen?
A moleculer glue between activated GPIIa/IIIb
What are the three granules that platelets release?
1. Dense granules
2. Alpha granules
What is the function of GPIb-alpha on platelets?
Initial tethering of platelet
What is the function of GPVI on platelets? What does it bind to?
Binds collagen to initially activate platelet and release ADP, 5HT, and TXA2
What is the fuction of GPIIb/IIa on platelets?
Facilitates platelet-platelet interactions whn joined with fibrinogen
What is the active drug in plavex?
Why is it important that clotting be reversible?
So that clots can be destroyed in places not needed
What is thrombosis?
Inappropriate clot formation
True or false: the coagulation and anticoagulation systems act in isolation of each other
How does vasoconstriction aid in the process of a clot formation?
Allows blood to flow more slowly, and allow platelets to have a better chance of adhering to an injury site
How do platelets adhere to the site of vessel injury?
Through cell surface glycoproteins activation, forming finger-like extensions
How do platelets recruit more of themselves to the site of injury?
Release factors (ADP and Ca)
What is the function of the initial platelet response? How strong is this?
Form a platelet plug--not very strong initially
Where is von Willebrand factor found? What does it do?
Found in the plasma and ECM, until it encounters exposed collage in the ECM. It binds to this, and recruits platelets
What happens to the platelet after it binds to vWF?
The GPVI binds to collagen in the ECM injury site
What does the platelet produce to recruit more of itself?
ADP, serotonin, and thromboxane A2
What is the function of the factors that platelets produce (ADP, serotonin, and thromboxane A2) when bound to the ECM?
bind to G-protein coupled receptors on platelets already adhering to the injury site, to further activate them
What is the function of GPVI on platelets?
Binds to the collagen in the ECM
What is the protein that is on platelets that, when activated, allows for binding of fibrinogen?
What is the function of the GPII/IIb protein found on platelets?
What is fibrinogen? Where is it produced and found?
Molecular glue for platelets
Produced by liver
Found in circulation in high amounts
What is the function of GpIIb/IIIa inhibitors in treating MIs?
Inhibit platelet aggregation that occurs
What is the function of the purinergic P2Y12 receptors on platelets? What is it activated by?
Activated by ADP, and facilitates the aggregation of platelets
What is the MOA of Plavex?
Antagonist to P2Y12
What are the three G-coupled protein receptors on platelets?
Protease activated receptors
Thromboxane A2 receptors
What are the two chemicals released by endothelial cells to inhibit platelet aggregation?
What do NO and PGI2 do after release from endothelial cells?
Prevent platelet adhesion
What is the charge on platelets? Endothelial cells? Why is this significant?
Both negative, meaning they repel each other when there is no damage
What is the end result of the platelet system?
Loose platelet clot
What is the function of the coagulation system? How does this compare to the platelet system?
Form insoluble fibrin clots that are much more secure than platelet plugs
What is the protein from the coag system that cross links and forms a meshwork to trap blood and serum in a clot?
What is the precursor form of fibrin? How is it turned into fibrin?
Fibrinogen, cleaved by a protease-Thrombin
What is the function of thrombin? (2)
Cleaves fibrinogen to form fibrin monomers
Activates Factor XIII
What activates factor XIII? What does it do?
Induces fibrin fibers to cross-link, forming a stable blood clot
What is the precursor form of thrombin? How does it become activated?
Formed by a complex cascade of coag factors
What are the descriptive names for factors I, II, III, and IV?
I = Fibrinogen
II = Prothrombin
III = Tissue factors
IV = Ca
Where is prothrombin found? What produces it?
What are the two pathways that activate Prothrombin?
What starts the extrinsic pathway?
What happens in the extrinsic pathway after the initial tissue damage (and factor III release)?
Factor VII activated
What does factor VII do in the extrinsic pathway?
Activates factor X
What does factor X do in the extrinsic pathway?
Activates factor 5, then thrombin
What is the composition of tissue factor complex in the extrinsic pathway?
Activates factor X
How can thrombin increase the rate of the extrinsic pathway activation?
Increases factor V
What are the four components of the prothrombin activator complex? What does it do?
Factors X and V, Ca, and phospholipids
Increases thrombin activation
How does the small amount of thrombin that is induced from the extrinsic pathway lead to an autocrine-like action to increase its activity?
Form the prothrombin activator complex
How is the intrinsic pathway begun? What is the first factor to be activated?
Exposure of collagen leads to the activation of factor 12
What is the order of activation of the factors in the intrinsic pathway?
12, 11, 9, 10
What happens after factor 9 activation in the intrinsic coag pathway? How fast is this?
Factor 10 is activated slowly
What does factor 10 activated in the extrinsic and intrinsic pathway?
Activates prothrombin into thrombin
What are the components of the tenase complex in the intrinsic pathway?
factors 9 and 8
Hemophilia A is caused by a deficiency in what factor? What does this inhibit the assembly of?
Thus there is no tenase complex
Where do the extrinsic and intrinsic pathway converge?
at factor X
Which factors require vitamin K for the activity?
2, 7, 9, and 10 (vit K was born in 1972, iff 1=10) also, S and C proteins
What is the purpose of vit K in the production of coag factors?
Used as a cofactor in the carboxylation of key glutamate residues in the factors (allows Ca to bind)
What is the MOA of Warfarin?
Blocks the reduction of Vit K after Vit K has been oxidized in the production of coag factors
Why are newborns and liver pts given Vit K?
Vit K comes from gut flora and is fat soluble. If there is no flora (babes) or if there is no bile to take up fatty soluble vit K, then vit K deficiency results
What does the activated partial thromboplastin time (aPTT or PTT) measure?
The speed of the intrinsic pathway
How is the PTT done?
Pt's anticoagulated plasma is placed in tube and mixed with phospholipids and a negatively charged bead. Ca is added later to initiate clotting
What does the prothrombin time (PT) measure?
The speed of the intrinsic pathway
How is the prothrombin time measurement performed?
Pt's blood is collected into citrated anticoagulant. Then Ca is added in the presence of thromboplastin and time is measured
What is the function of thrombomodulin?
Interacts with thrombin to inactivate it, by converting thromin into an anticoagulant enzyme
Where is thrombomodulin found?
On endothelial cells
What is the function of protein C? What activates it?
Activated by thrombomodulin/thrombin complex that degrades Factors Va and VIIIa
What is factor V leiden thrombophilia?
Mutation in factor V prevents it from being inactivated by protein C complex
What would be the consequence of a deficiency in protein C?
What would a deficiency in thrombomodulin cause?
What is the tissue factor that is secreted by endothelial cells, that reduces thrombin formation by inhibiting factor VIIa/tissue factor complex?
Tissue factor pathway inhibitor (TFPI)
What is antithrombin (type of molecule, what produces it, where its found), and how does it work?
It is a circulating protease produced by the liver, that inhibits thrombin production, and destroys thrombin
What does antithrombin need in order to become activated?
True or false: heparin and antithrombin both have anticoagulation effects alone, but work faster when bound together
False- antithrombin is slow, but works
Heparin has no intrinsic anticoagulation effect
Where is heparin sulfate usually found?
Endothelial cells surface in low quantities
What is the function of the fibrinolytic system? When and where does it work?
Degradation of fibrin clots (after an injury has healed or in inappropriate places)
What is the main protease that cleaves fibrin is what?
What is the inactivated state of plasmin? Where is it found, and what organ produces it?
Plasminogen, which is produced by the liver and is found circulating in the blood or in a clot
What activates plasminogen to plasmin? Where is this substance produced?
tPA (tissue Plasminogen Activator)
Produced by vascular endothelial cells
What are the two factors that inhibit tPA? Where are each of these found?
Plasminogen activator inhibitor (PAI)- endothelial cells
Alpha-2-plasmin inhibitor - circulation
What happens to plasminogen when a clot form via platelets and fibrin? What happens when the clot produces tPA?
Become enmeshed in the clot.
When the clot slowly increases tPA production, allows plasminogen to become activated, and breaks up the clot
Deficiency in which factor produces hemophilia A and which for B? What is the inheritance pattern of this?
This is an X-linked recessive trait
Which are the factors involved in the extrinsic pathway (in order)?
What are the factors that are in the intrinsic pathway (in order)?
Which clotting factor(s) is/are at the end of both the intrinsic and extrinsic pathway? What does this/ do these do?
factor 10 and 5
These combine to form the prothrombin activator
What are the two factors that make up the prothrombin activator complex?
10 and 5
Which clotting factor(s) is/are inhibited by thrombomodulin?
factor 5 and 8
Describe the pathway that thrombomodulin takes to inhibit factor 5. (3ish steps)
Thrombomodulin bind thrombin
activation of protein C, then S
Where is antithrombin found? Where is heparin found? What is the effect of them binding?
Antithrombin is circulating in the tissue
Heparin is on endothelial cell
Binding increases antithrombin activity
What is the condition where there is not enough platelets to form a clot? What are the symptoms of severe cases of this?
Small purpurea d/t many tiny hemorrhages
What is the effect of liver disease on clotting factors? How is this effected?
Reduces platelets and clotting factors through a lack of vit K uptake
What is the enzyme that reduces Vit K back to its usable form?
What is the MOA of asprin's anticoagulant ability?
What are the pro-aggregation factors for platelets?
2. Lower Blood flow
What are the anti-aggregation factors for platelets?
1. PGI2 and NO
2. Higher blood flow
What is bernard-Soulier syndrome?
A deficiency of GpIb, resulting in a lack of coagulation
What is the drug that blocks GpIIb/IIIa?
What is Glanzmann thrombasthenia?
A deficiency of GpIIb/IIIa