Hemostasis & Thrombosis Flashcards
what is hemostasis?
maintenance of clot-free blood within the vascular system while allowing for the formation of a solid plug of blood under conditions of vessel wall injury
what are the key players in hemostasis?
vascular endothelium
platelets
coagulation system
what are the 4 anti-platelet effects of intact endothelium?
- insulates platelets from subendothelial collagen
- prostacyclin (PGI2) synthesis
- ADPase synthesis
- nitric oxide synthesis
what does prostacyclin (PGI2) do?
inhibits platelet aggregation
what does ADPase synthesis do?
inhibits platelet aggregation
what does nitric oxide synthesis do?
vasodilation and inhibits platelet aggregation
what molecule activates anti-thrombin III?
heparin like molecule
what effect does heparin-like molecule have on intact endothelium?
anti-coagulant
what does anti-thrombin III do?
degrades thrombin
what does tissue plasminogen activator (t-PA) do?
converts plasminogen to plasmin
what property does t-PA have?
fibrinolytic property of INTACT endothelium
what does plasmin do?
degrades fibrin
what are the 4 pro-thrombotic properties of damaged endothelium?
- von willebrand factor synthesis
- tissue factor synthesis
- platelet activating factor (PAF)
- t-PA inhibitor synthesis
what does von Willebrands factor do?
essential for platelet adhesion
what does tissue factor do?
glycoprotein which activates coagulation system
what are the “bricks” of a thrombus?
platelets
what are the molecules that are secreted by platelets that cause activation of platelets?
- thromboxane (TXA2)
- ADP
- clotting factors V and VIII
- calcium
activated platelets bind to ____
vWF
activated platelets involved in initiation of the ____
coagulation cascade
how does a temporary clot become definitive?
formation of fibrin from thrombin = fused mass of platelets
what is the coagulation system activated by?
factor XII or tissue factor
what is the end product of coagulation system?
fibrin monomers
fibrin is the “____” of a thrombus
cement
what is thrombosis?
pathological aggregate of platelets, fibrin and blood cells within the non-interrupted vascular system (where a clot should not be / not a problem here)
what is a thrombosis adherent to?
vascular endothelium
T/F: thrombosis only arise in veins
F: arterial or venous circulation
what are the 3 predisposing factors to thrombi?
- damage to endothelium
- alterations in normal blood flow
- increased coagulability of blood
what is another name for the 3 predisposing factors to a thrombi?
virchow’s triad
what is laminar flow?
normal (good) flow in a blood vessel
what kind of flow has an obstruction of a blood vessel on either side of it?
turbulent flow
what does turbulent flow increase the risk of?
endothelial damage
what are 4 things that can lead to damage of the endothelium?
- ischemic damage to endocardium
- valvular damage
- free radical induced damage (radiation, trauma, chemicals, microbes)
- hemodynamic stress —-> high BP (more energy hitting the walls
name 2 types of alterations in normal blood flow
stasis & turbulence
what do alterations in normal blood flow cause?
- physical damage to endothelium
- disrupts laminar flow
- prevent renal clearance of coagulation proteins
- retards flow of anticoagulants to stie of injury
what are some examples of causes of increased coagulability of blood?
- genetic defect in anticoagulant proteins or coagulant proteins: Leiden Factor V (inherited hypercoagulability)
- activated protein C (APC) resistance – Factor V Leiden
- MTHFR gene (higher risk of heart disease since unable to metabolize homocysteine)
- neoplasia (release of procoagulants)
- polycythemia vera (^viscosity)
- smoking, obesity (soft risks)
what causes Activated protein C (APC) resistance — factor V leiden
A point mutation in the factor V gene (factor V Leiden) renders it resistant to inhibition by APC
_____ action is the most common genetic hypercoagulability disorder and accounts for up to ______ % of patients with venous thrombosis
Resistance APC
65%
