Hemostasis Part 1 (complete)

Question 1

What is meant by the term hemostasis?

Answer 1

• Ability of the body to stop bleeding from a damaged vessel

- From when it occurs => eventually repair it (restores normal blood flow)

Question 2

List the different components involved in the hemostatic process

Answer 2

1) Coagulation cascade
2) Anticoagulation regulatory pathways
3) Fibrinolytic system
4) Endothelial cell lining of blood vessels
5) Platelets

Question 3

Which coag factors are serine proteases?

Answer 3

• Prekallikrein
• Factor 2
• Factor 7
• Factor 9-13

Question 4

What are the properties of serine proteases in the coag cascade?

Answer 4

• Related to trypsin/chymotrypsin
• Exist in plasma as precursor zymogens
• Activated through proteolytic cleavage by active enzymes
• Cleave targets at arginine residues

Question 5

What is the exception to the general properties of serine proteases in the coag cascade?

Answer 5

Factor 13

• it’s a transglutaminase
• Forms amide bonds btwn specific lysine-glutamines of fibrin to make a stable clot

Question 6

Which coag factors are cofactors?

Answer 6

• HMWK
• Tissue Factor
• Factor 5
• Factor 8

Question 7

What are the properties of cofactors in the coag cascade?

Answer 7

• Lack intrinsic enzymatic activity
• Act as receptors for other components of enzyme complexes
• This speeds rxns 100s-fold to 1000s-fold

Question 8

List the different components of the intrinsic tenase complex

Answer 8

• Factor 9a
• Factor 8a
• Phospholipid
• Calcium

Question 9

List the different components of the extrinsic tenase complex

Answer 9

• Tissue factor
• Factor 7a
• Calcium

Question 10

List the different components of the prothrombinase complex

Answer 10

• Factor 10a
• Factor 5a
• Calcium

Question 11

Explain the role of the different components of the intrinsic tenase complex

Answer 11

To activate Factor 10

50 to 100x’s faster than the extrinsic tenase complex (at activating Factor 10)

Question 12

Explain the role of the different components of the extrinsic tenase complex

Answer 12

To activate Factor 9 or 10

Less efficient at activating Factor 10 than intrinsic tenase complex

Question 13

Explain the role of the different components of the prothrombinase complex

Answer 13

To activate Factor 2 (prothrombin) to 2a (thrombin)

Question 14

Explain the role of vitamin K in coagulation

Answer 14

• Vit K is required for post-translational modification of many coag proteins
• Vit K deficiency = problems with the cascade

Question 15

What are the factors that are vitamin K dependent?

Answer 15

• Factor 2
• Factor 7
• Factor 9
• Factor 10
• Protein C
• Protein S

Question 16

Describe how fibrinogen is converted to fibrin by thrombin leading to formation of an insoluble fibrin network

Answer 16

• Thrombin cleaves fibrinopeptide A and B
• Creates exposure of the site where the A/B used to be
• Leads to fibrin polymerization

GO LOOK AT THE PPT IMAGE (worth a thousand words!)

Question 17

Describe how factor 13 functions in stabilizing the forming clot

Answer 17

Factor 13 covalently cross-links ends (D peptide) of each fibrin molecule => stabilization

Question 18

What are the two main functions of von Willebrand factor in coagulation?

Answer 18

• Platelet adhesion and aggregation

- Binds to and protects Factor 13 (prolongs free flowing 13’s t1/2 – 12 hrs vs 2hrs)

Question 19

What are the components of the extrinsic coagulation pathway?

Answer 19

• Tissue Factor

- Factor 7

Question 20

What are the components of the intrinsic coagulation pathway?

Answer 20

• Prekallikrein
• HMWK
• Factor 12
• Factor 11
• Factor 9
• Factor 8

Question 21

How does the extrinsic coagulation pathway relate to the PT coagulation screening tests?

Answer 21

Prothrombin Time (PT) tests the extrinsic pathway function

Question 22

How does the intrinsic coagulation pathway relate to the APTT coagulation screening tests?

Answer 22

Activated partial thromboplastin time (APTT) tests the intrinsic pathway function

Question 23

Describe initiation phase of the coagulation cascade

Answer 23

• TF on cell surface
• 7a binds to TF (extrinsic tenase)
• [7a+TF] bind 10 => 10a
• [7a+TF] bind 9 => 9a
• [7a+TF] bind 7 => 7a
• 10a binds 5a (prothrombinase)
• [10a+5a] binds 2 => 2a (thrombin)

Question 24

Describe the amplification phase of the coagulation cascade

Answer 24

• 2a (from initiation) binds 8 => 8a
• 8a binds to activated platelet
• 11 binds 9 => 9a
• 9a binds 8a (on platelet surface)
• 2a binds 5 => 5a
• 5a binds to activated platelet surface

Remember 5a and 8a are cofactors

Question 25

Describe the propagation phase of the coagulation cascade

Answer 25

- 8a binds to 9a (intrinsic tenase) - [8a+9a] bind 10 => 10a (creates a shit ton of 10a --- 50-100x faster than extrinsic pathway) - [10a+5a] bind 2 => even more 2a (thrombin) - 2a cleaves fibrinopeptides => fibrin - 2a binds 13 => 13a (covalently links fibrin polymer)

Question 26

Why is thrombin considered the central enzyme in blood coagulation?

Answer 26

- Cleaves fibrinogen to fibrin - Also activates a bunch of factors (5, 8, 11, 13) - Also most potent known activator of platelets