Coagulation/ Hemostasis Flashcards
Name 3 components hemostatic system
- Circulating blood
- Endothelium matrix
- Sub endothelium matrix
Morphologically describe platelet
Anuclear
Discoid-shaped
Subcellular fragments of megakaryocytes
T/F The platelet plasma membrane, with its asymmetrical composition, plays a significant role in cell signaling and thrombin generation
True
4 components of primary coagulation
- Endothelium
- Inner lining of blood vessels
- Platelets
- Extracellular matrix components of the endothelium
What are the stages in three-stage model of platelet activation?
- initiation
- Extension
- Stabilization
[Primary hemostasis] Explain initiation process - 6 steps:
1- Exposition of subendothelial fibronectin, laminin and vWF
2- Shear stress leads to conformational changes in vWF
3- Plasma vWF is cleaved and immobilized on collagen, capture platelets at vascular lesions
4- VWF and platelet glycoprotein results in tethering and rolling of platelets along the endothelium
5- As velocity of rolling decreases, bonds between vWF and glycoprotein increases and strengthen
6- Finally this leads to adhesion and formation platelet monolayer
[Primary hemostasis] Explain extension process - 5 steps:
1- Formation of procoagulant membrane
2- Integrin activation
3- Local accumulation of thrombin
4- Secretion of thromboxane A2 and ADP: activation of nearby platelets
5- initiate platelet aggregation facilitated by conformational changes
[Primary hemostasis] Explain Stabilization process- 3 steps:
- Firm adhesion to fibrinogen via platelet integrins leading to clustering
- Actin/myosin filament strengthen the plt-to-plt interaction narrowing the gap between platelets
- Clot contraction caused by fibrin deposition
What is the end goal of secondary hemostasis?
Stable fibrin clot
[Cell-based model of coagulation] Summary of the main events of initiation
- TF (tissue factor) come into contact with FVIIa
- FVIIa facilitates formation of small amount of thrombin (FIIa)
[Cell-based model of coagulation] Summary of the main events of amplification
- Thrombin (FIIa) activates platlets to degranulate and externalize phosphatidylserine
- Facilitates their adhesion to subendothelial matrixes
- Activates factors V, VIII, XI
[Cell-based model of coagulation] Summary of the main events of propagation
- Formation of tenase (FIXa - FVIIIa)
- Formation of prrothrombinase complex (FXa - FVa)
- Massive formation of thrombin
[Cell-based model of coagulation] Summary of the main events of termination
- Endogenous anticoagulants counters thrombin generation
- Tissue factor pathway inhibitor (TFPI)
- Protein C (PC)
- Protein S (PS)
- Antithrombin
What are the primary initiators of fibrinolysis?
Tissue plasminogen activator (tPA) and urinary type plasminogen activator
Which is the most important inhibitor of fibrinolysis?
PAI-1 (plasminogen activator inhibitor 1)