Chapter 4: Coagulation factors

Question 1

What is the coagulation cascade?

Answer 1

The coagulation cascade is a series of amplifying enzymatic reactions that lead to the deposition of an insoluble fibrin clot

Question 2

Fill in: Each reaction step (of the coagulation cascade) involves an …. (an activated coagulation factor), a …. (an inactive proenzyme form of a coagulation factor), and a …. (a reaction accelerator).

Answer 2

enzyme, substrate and cofactor respectively

Question 3

Components (enzyme/substrate/cofactor) are assembled on a negatively/positively charged phospholipid surface

Answer 3

Negatively

Question 4

Assembly of reaction complexes also depends on a certain ion… which one? And how does it work?

Answer 4

Calcium, it binds to y(gamma)-carboxylated glutamic acid residues that are present in factors II, VII, IX and X

Question 5

The coagulation cascade can be divided into two pathways (in the laboratory). What are these two?

Answer 5

Extrinsic and intrinsic pathways

Question 6

How is the intrinsic and extrinsic pathway triggered in the laboratory?

Answer 6

Intrinsic: phospholipids, calcium and negative-charged substance (e.g. glass beads)
Extrinsic: phospholipids, calcium and a source of tissue factor

Question 7

How is clotting triggered in vivo?

Answer 7

In vivo, tissue factor is the major initiator of coagulation, which is amplified by feedback loops involving thrombin.

Question 8

What happens at the end of the coagulation cascade?

Answer 8

Thrombin converts fibrinogen to a fibrin clot

Question 9

Will you please look at fig 4.7 :)

Answer 9

Yhesyes (and i’ll look at 4.8 while i’m at it tooo)

Question 10

What does the proghrombin time (PT) assay do?

Answer 10

It assesses the function of the proteins in the extrinsic pathway (factors VII, X, V, II (prothrombin, and fibrinogen)

The time for a fibrin to clot is measured

Question 11

What does the partial thromboplastin time (PTT) assay do?

Answer 11

It screens the function of the proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II and fibrinogen)

The time for a fibrin to clot is measured

Question 12

Are PT and PTT a great way to evaluate coagulation factor function in patients?

Answer 12

Although they are great utility in evaulating the coagulation factors, they do not recapitulate the events that lead to coagulation in vivo

Question 13

Thrombin has many qualities. What does it do?

for a visualizer see fig 4.9

Answer 13

• Conversion of fibrinogen into crosslinked fibrin.
• Platelet activation.
• Proinflammatory effects.
• Anti-coagulant effects.

Question 14

The coagulation cascade sets another cascade in motion that limits the size of the clot. What is this cascade?

Answer 14

Fibrinolytic cascade

Question 15

How is studied which factor is important in the cascade?

Answer 15

They evaluatie the symptoms (mild/severe bleeding e.g.) in patients with a factor … deficiency

Question 16

Fibronolysis is largely accomplished through enzymatic activity. Which enzyme? And what does it do?

Answer 16

Plasmin (which breaks down fibrin and interferes with its polymerization)

Question 17

An elevated level of breakdown products of fibrinogen (often called fibrin split products), most notably fibrin-derived D-dimers, are a useful clinical marker. What does it mark?

Answer 17

Several thrombotic states

Question 18

What is the precursor of plasmin? How is it activated?

Answer 18

plasminogen, by factor XII-dependent pathway / plasminogen activators / t-PA

Question 19

To conclude, how is the coagulation restricted to sites of vascular injury?

Answer 19

• limiting enzymatic activation to phospholipid surfaces provided by activated platelets or endothelium,
• circulating inhibitors of coagulation factors, such as anti-
thrombin III, whose activity is augmented by heparin-like
molecules expressed on endothelial cells
• expression of thrombomodulin on normal endothelial cells,
which bind thrombin and convert it into an anti-coagulant,
• activation of fibrinolytic pathways (e.g., by association of
tissue plasminogen activator with fibrin).

Question 20

Will you also take a look at fig 4.10

Answer 20

OKok