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)
Factors present in intrinsic pathway
XII, XI, IX, VIII
Factors present in extrinsic pathway
VIIa, Tissue Factor
Factors present in common pathway
X, V, prothrombin (II), fibrinogen (I), XIII