Hemostasis Part 1 (complete) Flashcards
What is meant by the term hemostasis?
- Ability of the body to stop bleeding from a damaged vessel
- From when it occurs => eventually repair it (restores normal blood flow)
List the different components involved in the hemostatic process
1) Coagulation cascade
2) Anticoagulation regulatory pathways
3) Fibrinolytic system
4) Endothelial cell lining of blood vessels
5) Platelets
Which coag factors are serine proteases?
- Prekallikrein
- Factor 2
- Factor 7
- Factor 9-13
What are the properties of serine proteases in the coag cascade?
- Related to trypsin/chymotrypsin
- Exist in plasma as precursor zymogens
- Activated through proteolytic cleavage by active enzymes
- Cleave targets at arginine residues
What is the exception to the general properties of serine proteases in the coag cascade?
Factor 13
- it’s a transglutaminase
- Forms amide bonds btwn specific lysine-glutamines of fibrin to make a stable clot
Which coag factors are cofactors?
- HMWK
- Tissue Factor
- Factor 5
- Factor 8
What are the properties of cofactors in the coag cascade?
- Lack intrinsic enzymatic activity
- Act as receptors for other components of enzyme complexes
- This speeds rxns 100s-fold to 1000s-fold
List the different components of the intrinsic tenase complex
- Factor 9a
- Factor 8a
- Phospholipid
- Calcium
List the different components of the extrinsic tenase complex
- Tissue factor
- Factor 7a
- Calcium
List the different components of the prothrombinase complex
- Factor 10a
- Factor 5a
- Calcium
Explain the role of the different components of the intrinsic tenase complex
To activate Factor 10
50 to 100x’s faster than the extrinsic tenase complex (at activating Factor 10)
Explain the role of the different components of the extrinsic tenase complex
To activate Factor 9 or 10
Less efficient at activating Factor 10 than intrinsic tenase complex
Explain the role of the different components of the prothrombinase complex
To activate Factor 2 (prothrombin) to 2a (thrombin)
Explain the role of vitamin K in coagulation
- Vit K is required for post-translational modification of many coag proteins
- Vit K deficiency = problems with the cascade
What are the factors that are vitamin K dependent?
- Factor 2
- Factor 7
- Factor 9
- Factor 10
- Protein C
- Protein S
Describe how fibrinogen is converted to fibrin by thrombin leading to formation of an insoluble fibrin network
- 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!)
Describe how factor 13 functions in stabilizing the forming clot
Factor 13 covalently cross-links ends (D peptide) of each fibrin molecule => stabilization
What are the two main functions of von Willebrand factor in coagulation?
- Platelet adhesion and aggregation
- Binds to and protects Factor 13 (prolongs free flowing 13’s t1/2 – 12 hrs vs 2hrs)
What are the components of the extrinsic coagulation pathway?
- Tissue Factor
- Factor 7
What are the components of the intrinsic coagulation pathway?
- Prekallikrein
- HMWK
- Factor 12
- Factor 11
- Factor 9
- Factor 8
How does the extrinsic coagulation pathway relate to the PT coagulation screening tests?
Prothrombin Time (PT) tests the extrinsic pathway function
How does the intrinsic coagulation pathway relate to the APTT coagulation screening tests?
Activated partial thromboplastin time (APTT) tests the intrinsic pathway function
Describe initiation phase of the coagulation cascade
- 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)
Describe the amplification phase of the coagulation cascade
- 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
