Hemostasis Flashcards
What is primary hemostasis?
Aggregation of platelets at injury site, forming a plug
What is secondary hemostasis?
Initial platelet plug is enlarged and stabilized by adding a structural matrix of fibrin (coagulation cascade)
What is antithrombosis?
Process of stopping clot formation once an effective clot has formed.
What is fibrinolysis?
The degradation of the clot to restore normal blood flow.
What are platelets derived from?
Megakaryocytes
What hormone is responsible for signaling platelet production and where is it generated?
Thrombopoietin,and it is generated in the kidney and liver
How is Thrombopoietin activity regulated?
Platelets express thrombopoietin receptors as well as megakaryocytes.
When there is a high amount of circulating platelets, thrombopoietin becomes primarily bound to platelets, which consume the signal preventing it reaching megakaryocytes.
When there is a low amount of circulating platelets, thrombopoietin is not getting destroyed by platelets and instead binds with megakaryocytes, signaling platelet production.
What does von Willebrand factor do?
It is a circulating plasma protein that binds to exposed collagen when a vessel injury occurs.
When bound to the collagen, it undergoes a conformational change that allows for platelet binding.
What does platelet-derived growth factor do?
It induces fibroblasts to grow in areas of damage.
Fibroblasts become smooth muscle and endothelial cells to close the hole.
What does plasmin do?
Breaks apart fibrin polymers, destroying clots
How is plasmin regulated?
Plasminogen is the inactive form that circulates in the blood.
Damaged tissue releases Tissue Plasminogen Activator (tPA) which will normally form active plasmin from plasminogen, allowing destruction of clots.
However, tPA inhibitor (also circulating in the blood) prevents this from happening (ensuring the clot has had sufficient time to fix the hole).
How is tPA inhibitor regulated?
Thrombin activates Protein C
Activated Protein C inactivates tPA inhibitor, allowing Plasmin activating and destruction of fibrin polymers.
Describe the Extrinsic Pathway
Tissue factor (III) promotes the activation of VII to VIIa and forms a complex with it.
VIIa/III complex activates X to Xa.
Describe the Intrinsic Pathway
XII is activated to XIIa.
XIIa catalyzes the activation of XI to XIa.
XI catalyzes the activation of IX to IXa.
IXa forms a complex with VIIIa, which then activates X to Xa
Describe the Common Pathway
Xa, with the help of Va, catalyzes the activation of II (Prothrombin) to IIa (Thrombin).
IIa catalyzes the activation of I (Fibrinogen) to Ia (Fibrin) and also catalyzes the activation of XIII to XIIIa
XIIIa catalyzes the formation of cross-linked fibrin strands