Thrombosis Flashcards
(24 cards)
What is haemostasis?
The mechanism that leads to cessation of bleeding from a blood vessel
What are the 3 substances in the body that help with vascular control of platelet function?
Nitric oxide - released by platelets and endothelium to stop inappropriate platelet activation
Prostacyclin - produced by endothelial cells that act negatively on platelets to stop activation
Thromboxane - can be released by platelets to cause smooth muscle cell constriction and platelet aggregation
What are the 2 parts of haemostasis?
Platelet aggregation and vasoconstriction + clotting cascade
What happens to cause the formation of soft platelet plug?
Damage to blood vessel = exposure of platelets to collagen, vWF in ECM, and thrombin = platelets adhere and activate = release of mediators (cause more adhesion and activation) = vasoconstriction and platelate aggregation = formation of soft platelet plug
What are the 2 parts of the clotting cascade?
Initiation (extrinsic pathway) + amplification and propagation (intrinsic pathway)
What activates the initiation part of the clotting cascade? What does it involve and when does it happen?
It is activated by Tissue Factor (TF) and takes place on TF-expressing cells in tissues after blood and clotting factors leak out of the blood vessel.
What initiated the amplification and propagation part of the clotting cascade? What does it involve and where does it happen?
It is initiated by thrombin and activates several clotting factors. It takes place on activated platelets.
What is the difference between arterial and venous thrombosis?
Arterial thrombosis - white clots that are usually associated with atherosclerosis, large platelet component, prophylaxis with anti-platelet drugs
Venous thrombosis - red clots associated with stasis of blood after surgery or trauma, has RBC component and large fibrin component, prophylaxis with anti-coagulants
Why does the clotting cascade have multiple pathways?
To provide an accelerant to create thrombin as rapidly as possible for survival, to provide multiple points of control
What do anti-platelet drugs do? What does it act on?
Limit growth or reduce risk of arterial thrombosis by inhibiting platelet aggregation
COX inhibitor (aspirin): mechanism of action, adverse effects, and contraindications
MoA - irreversible inhibition of COX1 = doesn’t allow production of prostaglandin = no production of TXA2 (potent platelet agonist) = less sticky platelets = less sticking of platelets to lumen of artery & forming a thrombus
P2Y12 receptor antagonists (clopidogrel): mechanism of action, adverse effects, and contraindications
MoA - blocks P2Y12 platelet receptor = no ADP binding to receptor = no platelet activation and aggregation
GP2b-3a antagonists: mechanism of action, adverse effects, and contraindications
MoA - block GP2b-3a receptors = competing with fibrinogen = inhibits platelet aggregation
AE - thrombocytopaenia (loss of platelets in blood), not for long term
When are anti-platelet drugs used?
For secondary prevention or to block restenosis after angioplasty
What is sub-optimal with current thrombosis therapy?
Limited clinical efficacy, variability in patient response and toxicity, and risk of major haemorrhage
What is secondary prevention?
A medical intervention to reduce the risk of an event re-occuring. For example, anti-platelet drugs are used to prevent a repeat of a thrombotic event.
What is anticoagulant and fibrinolytic therapy for?
Prophylaxis and treament of venous thrombi, they inhibit coagulation cascade and prevent the propagation of blood clot (don’t dissolve clots)
What can cause venous thrombi?
Decreased blood flow, endothelial disturbance and high blood coagubility
Stasis leads to less blood flow = prevents dilution of coagulation proteins
Heparin: mechanism of action, adverse effects, and contraindications
MoA - bind to antithrombin (AT) to make it an efficient inactivator of coagulation factors
Used for prevention and rapid treatment
Vitamin K antagonists (warfarin): mechanism of action, adverse effects, and contraindications
MoA - inhibits Vit K dependent epoxide reductase activity = depletion of Vit K-dependent coagulation factors
Long term anticoagulant therapy, orally active, must monitor frequently
AE - 1-3% have major bleeding events
Factor Xa inhibitor: mechanism of action, adverse effects, and contraindications
MoA - inhibit FXa = inhibits thrombin generation
Thrombin inhibitors: mechanism of action, adverse effects, and contraindications
MoA - block active site of thrombin = inhibits clot bound and free thrombin
What is a DOAC? Why is it more advantageous to take it compared to other anticoagulants?
Direct-acting Oral AntiCoagulants are highly effective, need less monitoring, has reduced risk of brain bleed
Fibrinolytics (clot busters): mechanism of action, adverse effects, and contraindications
MoA - activate plasminogen = activated process of digesting a thrombus or clot
AE - high risk of haemorrhage
