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
What factors does Fibrin (IIa) help activate?
Factor V Factor VII Factor VIII Factor XI Factor XIII
What does Protein C promote and how does it do this?
Protein C promotes anticoagulation by degrading Factors V and VII as well as by inactivating tPA (tissue plasminogen activator) inhibitor.
What are the Vitamin K dependent factors and what effect does Vitamin K deficiency have on coagulation?
Factor II, Factor VII, Factor IX, and Factor X, as well as Protein C.
Vitamin K deficiency reduces the ability to produce blood clots.
What molecules together form Tenase?
Factor IXa, Factor VIIIa, and Ca2+
What molecules together form Prothrombinase?
Factor Xa, factor Va, and Ca2+
What does an abnormal Prothrombin Time (PT) indicate?
Indicates there is a problem with either the factors in the common pathway (X, II, V, or I) OR the extrinsic pathway (VII)
What does an abnormal Partial Thromboplastin Time (PTT) indicate?
Indicates there is a problem with either the factors of the common pathway (X, V, II, or I) OR the intrinsic pathway (XII, XI, IX, or VIII).
What does Heparin do?
It is an anticoagulant. Blocks activity of Factors IIa, IX, and Xa.
What is hemophilia A?
A deficiency of Factor VIII
What is hemophilia B?
A deficiency of Factor IX
What does Warfarin do?
Anticoagulant that blocks the synthesis of vitamin K dependent factors
Factors II, VII, IX, and X
