Hemostasis and Thrombosis Flashcards
What is hemostasis?
Process initiated to arrest hemorrhage by forming a blood clot in response to vascular injury.
What is thrombosis?
Pathologic process leading to formation of a blood clot (thrombus) within the circulation
What is the general cause of thrombus formation? What for processes contribute?
Antithrombotic systems fail to balance prothrombotic processes
- Activation of platelets
- Activation of coag pathways
- Participation of monocyte/macrophage system
- Active involvement of the endothelial cells of the vessel walls
What is the endpoint goal of the coagulation cascade?
Conversion of fibrinogen to the fibrin polymer via the serine protease enzyme, “thrombin”
What is tissue factor and what is its role in the coagulation cascade? What inhibits it?
TF associates with Factor VIIa forming the TF:VIIa complex. TF:VIIa activates factors X and IX; TFPI inhibits the TF:VIIa complex
Describe the coagulation cascade. In the presence of what does Xa bind to Va? What complex does it form and what is the job of the complex?
Calcium; Prothrombinase Complex which promotes activation of prothrombin to thrombin
What anticoagulative properties does thrombin have?
- Produce fibrinolytic molecules
- Regulation of GFs
- Regulation of WBC adhesion molecules
- Mediates Protein C anticoag pathway
What angticoagulant properties does V have?
Modulates protein C system which downregulates VIIIa
Describe platelet actions in vascular injury
- Gp Ib (platelet protein) binds to vWF
- Platelets recruit other platelets thru ADP and TXA2
- Platelets bind to each other thru GpIIb/IIIa -fibrinogen-GpIIb/IIIa binding
What are the functions of NO and Prostacyclin (PGI2) in the coagulation cascade?
- NO - inhibits platelet agg and adhesion to vessels
- PGI2 - inhibits platelet agg
What activates antithrombin? What is the mechanism of antithrombin?
Endothelial heparan sulfate; Binds IIa, IXa, Xa, Xia, and XIIa
By what means does thrombin help to terminate the coagulation cascade?
Thrombin attaches to thrombomodulin (receptor on endothelial cells). Thrombomodulin then activates Protein C which destroys V and VIII
What are the three general major causes of thrombus formation?
- Endothelial continuity is lost
- Endothelial function is altered
- Blood flow in a vessel becomes abnormal
What is the most common denuding injury to the endothelium?
Atherosclerotic plauqes
What are the 4 fates of a thrombus?
- Lysis
- Growth and Propagation
- Embolization
- Organization and Canalization