Coagulation Cascade

Question 1

what type of enzymes are most of the enzymes in the coagulation cascade?

Answer 1

serine proteases

they hydrolyze peptide bonds using a serine residue at their active center

Question 2

what are the coagulation factors in the coagulation cascade?

Answer 2

II, VII, IX, X, XI, XII, and XIII

II = thrombin

Question 3

what do cofactors do in the coagulation cascade?

Answer 3

they amplify the coagulation cascade

Question 4

what are the cofactors in the coagulation cascade?

Answer 4

TF = tissue factor

TFV

TFVIII

usually just called “factors” too

Question 5

what happens during the coagulation cascade?

Answer 5

the coagulation cascade is a series of factors which activate each other in a cascade fashion

the whole point of the cascade is to turn fibrinogen into fibrin, so we can seal up the platelet plug we just made

summary: TF help turn fibrinogen into fibrin

Question 6

does your body usually use the extrinsic or intrinsic pathway to make fibrin?

Answer 6

the two pathways are big-time co-dependent

In vivo, we need to have both intrinsic and extrinsic pathways working correctly to make fibrin

Question 7

what is the main activator of the intrinsic pathway in vivo?

Answer 7

thrombin

Question 8

what is factor XII important for?

Answer 8

important in forming clots in test tubes

doesn’t play much of a role in vivo

Question 9

what happens to people with deficiencies of high molecular weight kininogen, prekallikrein, and factor XII?

Answer 9

nothing!

they don’t have bleeding disorders!

these factors are not crucial for activation of the intrinsic pathway in vivo

Question 10

what is the activator of the extrinsic pathway?

Answer 10

tissue factor

Question 11

what is tissue factor?

Answer 11

membrane protein that is found:

1. on cells that are normally not in contact with blood (like smooth muscle cells in the subendothelium and fibroblasts surrounding blood vessels). Vascular injury exposes this TF to the blood and initiates the coagulation cascade
2. in microparticles
3. on endothelial cells, and on monocytes, when there’s inflammation (but not under normal resting conditions – otherwise we’d be coagulating all over the place)

Question 12

what are micorparticles?

Answer 12

tissue factor is found in microparticles

they are little fragments of cell membrane found in normal blood

these microparticles have receptors for P-selectin

P-selectin is a cell adhesion molecule that lives in platelets and endothelial cells

When it’s activated, it flips to the outside of the cell membrane, and the microparticles stick to it, and tissue factor accumulates in the region of the forming clot.

Question 13

what does TF do?

Answer 13

TF binds to activated factor VII, and then this TF-VIIa complex kicks off the coagulation cascade via the extrinsic pathway

Question 14

What factors are involved in the extrinsic pathway?

Answer 14

tissue factor and factor VII

Question 15

What factors are involved in the intrinsic pathway?

Answer 15

factors XI, IX, and VIII

also involves factor XII, fibrinogen, prekallekarin and high molecular weight kininogen, although we don’t care too much about those because deficiencies in these don’t result in disease

Question 16

what factors are involved in the final common pathway?

Answer 16

factors X, V, II (thrombin) and I (fibrinogen)

can be activated by either the intrinsic or extrinsic pathway

Question 17

At what point in the coagulation cascade do both pathways converge?

Answer 17

At the activation of factor X

Question 18

what are the steps that happen when a vessel is injured?

Answer 18

1. first thing that happens is that tissue factor is exposed to the bloodstream, and the extrinsic pathway is activated
2. TF binds to factor VIIa and then that TF-VIIa complex converts factor X to Xa
3. Xa converts II to IIa
4. IIa converts fibrinogen to fibrin

Question 19

what happens when you make Xa via the extrinsic pathway?

Answer 19

as soon as we make a little bit of Xa using the extrinsic pathway, something called Tissue Factor Pathway Inhibitor (TFPI) shuts down the entire extrinsic pathway. Totally kills it

Question 20

what happens after the extrinsic pathway has been shut down?

Answer 20

the small bit of thrombin that was generated on the way to making fibrin is able to activate the intrinsic pathway

thrombin converts XI to XIa

then the process continues down the intrinsic and final common pathways which results in the formation of fibrin

factors V and VIII really amplify the intrinsic and final common pathways, respectively

Question 21

what does factor VIII do?

Answer 21

VIII –> VIIIa

VIIIa amplifies IXa

IXa activates X –> Xa

Question 22

what does factor V do?

Answer 22

amplifies the final common pathway

V –> Va

Va amplifies Xa

Xa activates II –> IIa

Question 23

what does thrombin do?

Answer 23

1. activates fibrinogen (I) –> fibrin (Ia) reaction

2. it activates factor XIII, which crosslinks the fibrin molecules that have been incorporated into the platelet plug

Question 24

At what event in the coagulation cascade do both intrinsic and extrinsic pathways combine to form the common pathway?

Answer 24

Conversion of factor X à Xa

Question 25

In the body, when a blood vessel is damaged, which of the following substances initiates the coagulation cascade?

Answer 25

Tissue factor

TF initiates coagulation along extrinsic pathway

Question 26

How does the cascade work in the body?

Answer 26

Tissue factor kicks off the extrinsic arm of the cascade, but this arm is soon shut off, and fibrin formation is completed using the intrinsic arm.