Hemostasis

Question 1

What is hemostasis? What are the 4 steps?

Answer 1

Process of blood clot formation at the site of vessel injury

1. Initiation and formation of platelet plug (thrombogenesis)
2. Clot propagation by coagulation cascade
3. Termination by antithrombotic control mechanisms
4. Removal of clot by fibrinolysis

Question 2

Platelet function can be regulated by these 3 categories of substances:

Answer 2

1. Substances outside the platelet
   - interact with plt membrane receptors
   - e.g. collagen, thrombin
2. Substances within the platelet:
   - interact with plt membrane receptors (e.g. ADP, PG, serotonin)
   - act within the plt (Thromboxane A2)

Question 3

What is the initial response of damaged blood vessel? Describe the process.

Answer 3

Vasospasm

• plt stick to exposed collagen of damaged epithelium = activation –> shape change to become adhesive
• conformational change in GP IIb/IIIa receptor on plt surface = fibrinogen bridging

Question 4

List two substances that platelets secrete once stimulated?

Answer 4

• Fibrinogen (local source)

- Thromboxane A2 - promotes VC and further plt aggregation

Question 5

What are the Vit K procoagulants? Which are anticoagulants? Which drug exerts its effects in this pathway?

Answer 5

Procoagulants:

• Prothrombin (Factor II)
• VII, IX, X
• all procoagulants (except VWF) produced in the liver

Anticoagulants:
- Protein C & S

Question 6

How is the extrinsic pathway initiated?

Answer 6

• Activated by TF exposed at injury site [serves as cofactor to activate factor VII production]
• • generation/exposure of TF at wound site is primary INITIATOR of clotting –> “primes” clotting cascade & activates platelets **
• TF-FVII complex activates factors IX & X
• Xa goes on to activate PT –> Thrombin

Question 7

What is the role of the Intrinsic pathway?

Answer 7

Factor XII, prekallikrein, and kininogen are activated by contact with negatively charge surfaces & AMPLIFY the process

Question 8

Where do the extrinsic and intrinsic pathways meet?

Answer 8

Both pathways converge on the activation of Factor X (converts PT –> Thrombin)

Thrombin then converts Fibrinogen –> Fibrin Clot

Question 9

What 2 circulating enzymes inhibitors are involved in the termination of the clotting cascade?

Answer 9

1. Antithrombin
   - plasma protease inhibitor
   - neutralizes thrombin (Factor IIa) and IXa, Xa, XIa, XIIa
2. TF pathway inhibitor (less important)

Question 10

What happens when thrombin (Factor IIa) binds to thrombomodulin?

Answer 10

Thrombin undergoes conformational change

Can now activate Protein C
- no longer promotes plt aggregation or cleavage of fibrinogen

Question 11

What happens when Protein C becomes activated?

Answer 11

Protein C (along with protein S) inactivate factors Va & VIIIa

Question 12

What happens when plasminogen binds to fibrin?

Answer 12

Plasminogen is converted to plasmin

Plasmin cleaves fibrin resulting in FDPs

Question 13

What lab do you use to measure FDPs? What does it indicate?

Answer 13

D-dimer

Anytime D-dimer is elevated = marker of some level of fibrinolysis
- indicates clotting has occurred