Thrombosis

Question 1

What is haemostasis?

Answer 1

The mechanism that leads to cessation of bleeding from a blood vessel

Question 2

What are the 3 substances in the body that help with vascular control of platelet function?

Answer 2

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

Question 3

What are the 2 parts of haemostasis?

Answer 3

Platelet aggregation and vasoconstriction + clotting cascade

Question 4

What happens to cause the formation of soft platelet plug?

Answer 4

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

Question 5

What are the 2 parts of the clotting cascade?

Answer 5

Initiation (extrinsic pathway) + amplification and propagation (intrinsic pathway)

Question 6

What activates the initiation part of the clotting cascade? What does it involve and when does it happen?

Answer 6

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.

Question 7

What initiated the amplification and propagation part of the clotting cascade? What does it involve and where does it happen?

Answer 7

It is initiated by thrombin and activates several clotting factors. It takes place on activated platelets.

Question 8

What is the difference between arterial and venous thrombosis?

Answer 8

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

Question 9

Why does the clotting cascade have multiple pathways?

Answer 9

To provide an accelerant to create thrombin as rapidly as possible for survival, to provide multiple points of control

Question 10

What do anti-platelet drugs do? What does it act on?

Answer 10

Limit growth or reduce risk of arterial thrombosis by inhibiting platelet aggregation

Question 11

COX inhibitor (aspirin): mechanism of action, adverse effects, and contraindications

Answer 11

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

Question 12

P2Y12 receptor antagonists (clopidogrel): mechanism of action, adverse effects, and contraindications

Answer 12

MoA - blocks P2Y12 platelet receptor = no ADP binding to receptor = no platelet activation and aggregation

Question 13

GP2b-3a antagonists: mechanism of action, adverse effects, and contraindications

Answer 13

MoA - block GP2b-3a receptors = competing with fibrinogen = inhibits platelet aggregation

AE - thrombocytopaenia (loss of platelets in blood), not for long term

Question 14

When are anti-platelet drugs used?

Answer 14

For secondary prevention or to block restenosis after angioplasty

Question 15

What is sub-optimal with current thrombosis therapy?

Answer 15

Limited clinical efficacy, variability in patient response and toxicity, and risk of major haemorrhage

Question 16

What is secondary prevention?

Answer 16

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.

Question 17

What is anticoagulant and fibrinolytic therapy for?

Answer 17

Prophylaxis and treament of venous thrombi, they inhibit coagulation cascade and prevent the propagation of blood clot (don’t dissolve clots)

Question 18

What can cause venous thrombi?

Answer 18

Decreased blood flow, endothelial disturbance and high blood coagubility

Stasis leads to less blood flow = prevents dilution of coagulation proteins

Question 19

Heparin: mechanism of action, adverse effects, and contraindications

Answer 19

MoA - bind to antithrombin (AT) to make it an efficient inactivator of coagulation factors

Used for prevention and rapid treatment

Question 20

Vitamin K antagonists (warfarin): mechanism of action, adverse effects, and contraindications

Answer 20

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

Question 21

Factor Xa inhibitor: mechanism of action, adverse effects, and contraindications

Answer 21

MoA - inhibit FXa = inhibits thrombin generation

Question 22

Thrombin inhibitors: mechanism of action, adverse effects, and contraindications

Answer 22

MoA - block active site of thrombin = inhibits clot bound and free thrombin

Question 23

What is a DOAC? Why is it more advantageous to take it compared to other anticoagulants?

Answer 23

Direct-acting Oral AntiCoagulants are highly effective, need less monitoring, has reduced risk of brain bleed

Question 24

Fibrinolytics (clot busters): mechanism of action, adverse effects, and contraindications

Answer 24

MoA - activate plasminogen = activated process of digesting a thrombus or clot

AE - high risk of haemorrhage