Anticoagulants

Question 1

What is hemostasis?

Answer 1

It is a process which causes bleeding to stop, meaning to keep the blood within a damage blood vessel. (The opposite of hemostasis is hemorrhage)

Question 2

What are the three steps to clot formation?

Answer 2

1. Vessel constriction
2. Platelet adhesion, activation and aggregation
3. Cross-linking of fibrin through the coagulation cascade

Question 3

Upon injury, vascular endothelial cells begin to produce what two things?

Answer 3

Prostaglandin F2a

Thromboxane A2

Question 4

What do Prostaglandin F2a and Thromboxane A2 do?

Answer 4

They are potent vasoconstrictors that act on smooth muscles. This helps to limit hemorrhage.

Question 5

What allows platelets to bind to the injured site?

Answer 5

The exposed extracellular matrix proteins allow platelets to bind.

Question 6

When platelets bind to the injured site, what happens to the platelets?

Answer 6

They are activated and secrete some more thromboxane A2 and prostaglandin F2a, ADP (for platelet aggregation) and serotonin (for vasoconstriction and platelet aggregation)

Question 7

The next few cards will be a little more in depth of the four steps of clot formation. Here we go.

Answer 7

I’m ready.

Question 8

In step 1 we get vessel constriction. What do the endothelial cells begin to produce to help with that?

Answer 8

Prostaglandin F2a and thromboxane A2- these are both potent vasoconstrictors. This helps to limit hemorrhage

Question 9

In step 2 we get platelet adhesion and activation. We already had a card on platelets binding to the exposed matrix proteins, but what happens when a platelet is activated?

Answer 9

It leads to a conformation change in an integral receptor that allows it to bind fibrinogen, a plasma protein. The platelets aggregate as a result of the fibrinogen cross linking.

Question 10

For step 3- as platelet aggregation and activation is taking place, what else is happening?

Answer 10

The intrinsic and extrinsic coagulation pathways are initiated. The extrinsic is most important

Question 11

In step 3, TF (tissue factor) binds what which does what?

Answer 11

TF binds Factor VII. This allows factor VII to be activated to Factor VIIa.

Question 12

In step 3, now that you’ve got some TF-VIIa, now what?

Answer 12

TF-VIIa can now activate Factors IX and X, but mostly IX.

Question 13

T/F all these factors only are activated when they are complexed with another factor or enzyme?

Answer 13

True

Question 14

The Xa-Va complex cleaves ________ into _____ which produces the enzyme that will create a blood clot.

Answer 14

prothrombin into thrombin

Question 15

What is the job of thrombin?

Answer 15

It cleaves fibrinogen which exposes binding sites. This results in the formation of a fibrin mesh.

Question 16

T/F thrombin also cleaves and activates clotting factors V, VIII, and XI?

Answer 16

True

Question 17

So thrombin comes around and hacks off little pieces of fibrinogen to expose some binding sites in the fibrin. You can’t just leave it there, so then what does thrombin do?

Answer 17

Then thrombin activates factor XIII, an enzyme that links the fibrin mesh. Now you’ve got a blood clot.

Question 18

Antithrombin (AT) is what?

Where’s it made?

Answer 18

It’s a small protein that inactivates several enzyme of the coagulation system.
It’s made in the liver.

Question 19

For the purpose of this lecture, what do serine proteases do?
So what would a serine protease inhibitor do?

Answer 19

They are prothrombins. They help coagulation occur.

A serine protease inhibitor would be an antithrombin agent to stop clotting.

Question 20

What is the tissue factor pathway inhibitor (TFPI)?

Answer 20

It’s a protein which can inhibit Factor Xa. TFPI can inhibit Xa. This would stop the coagulation/clotting cascade

Question 21

What is fibrinolysis?

Answer 21

It is the process that prevents blood clots from growing and becoming problematic

Question 22

Disseminated intravascular coagulation- what is it and what are its effects?

Answer 22

It’s just what it’s name says it is: it is widespread intravascular clotting that should not be happening. Many small blood vessels can be occluded, which can damage several organs. Since all the clotting factors are used up at these sites, a regular cut would lead to some severe bleeding instead of coagulation

Question 23

What are fibrinolytics?

Answer 23

They are used to lyse thrombi. They break down the fibrin mesh that is the blood clot. This can recanalize an occluded vessel

Question 24

A thrombolytic drug is heparin. What does it do?

Answer 24

Cool. It binds to antithrombin (which is made in the liver) and increases its activity 1000X

Question 25

Is regular heparin or low molecular weight heparin better?

Answer 25

the low molecular weight one

Question 26

There are direct and indirect thrombin inhibitors. What’s the difference?

Answer 26

Direct works directly on the clot where indirect works on something that works on the clot.

Question 27

In order for thrombin to become catalytically competent (and make clots) they must undergo a carboxylation reaction. How is this achieved?

Answer 27

It happens with the help of vitamin K. It must be oxidized. Then it gets reduced and oxidized again. This repeats and the vitamin K is essentially reused.

Question 28

What happens if you block the reduction of Vitamin K?

Answer 28

If you don’t reduce vitamin K, then the body funds out of reduced vitamin K and thrombin can’t become catalytically active.

Question 29

What does warfarin do?

Answer 29

It blocks the action that takes Vitamin K from the oxidized form to the reduced form so it can be used to activate thrombin. No clots under warfarin’s watch!

Question 30

If you took too much warfarin, what would be a good thing to do?

Answer 30

eat some vitamin K

Question 31

What does thromboxane A2 do?

Answer 31

It stimulates the activation of new platelets and increases platelet aggregation.

Question 32

What effect does aspirin have on thromboxane A2?

Answer 32

It inhibits its synthesis. That’s why it’s a blood thinner.

Question 33

If you have hereditary bleeding disorders that mess with your clotting factors, what do you do?

Answer 33

Be very careful or treat it by replacement therapy.