Anti-Thrombotics

Question 1

Function of Haemostasis in Damaged vessels

Answer 1

•Arrest of blood loss from damaged vessels

Haemosatsis is vital to life

Question 2

What occurs normally during Haemostasis

Answer 2

Platelets are circulating non-adhesively, and circulate singly.

During vessel wall injury, platelets become activated and aggregate, become stabilised by fibrin, and arrest bleeding from severed vessels (where clotting cascade become activated)

Platelet and clotting cascade activation occurs at the same time

Question 3

What is Thrombosis

Answer 3

•formation of occlusive thrombi leading to MI, ischaemic stroke.

Abnormalities occurring in the Haemostasis system

Question 4

Diagram for vascular control of platelet function

Answer 4

> platelet release mediators

> endothelial cells also release mediators

Regulation of smooth muscle contraction

Question 5

Describe the Aggregation of platelets + vasoconstriction step in (NORMAL) Haemostasis

Answer 5

1) damage to blood vessel wall, therefor blood loss
2) Exposure of platelets to collagen and vWF in extracellular matrix and (later) exposure to thrombin
3) Platelets adhere and activate (COX)
4) Release of mediators -5HT, TXA2, ADP - which increase 3)
5) Vasoconstriction + aggregation of platelets (3 phases: Adhesion -Collagen/vWF- Activation & Aggregation)
6) Formation of soft platelet plug (fibrinogen receptors)

Question 6

Describe the clotting pathway process in (NORMAL) Haemostasis

Answer 6

1) Initiation -activated by TF
2) Amplification & Propagation (Initiated by Thrombin(IIa) - produces 1000 fold)

(Several steps require Ca ions and phospholipid)

Question 7

Arterial vs Venous Thrombi

Answer 7

Arterial Thrombosis (white):

• Usually associated w Atherosclerosis
• Form at site of vascular injury/disturbed BF
• Large platelet component
• ProPhylaxis w Anti-platelet drugs
• Most causes of MI and 80% of strokes

Venous Thrombosis (red):

• Associated w stasis of blood or vascular injury following surgery/trauma
• Platelet component, Large fibrin component
• RBC component
• ProPhylaxis w Anti-Coagulants
• 3rd leading cause of CV associated death

Question 8

Plaque vulnerability, disruption and Thrombosis

Answer 8

Vulnerable plaque - Lipid-rich core, body tries responding by producing Fibrous cap

Cap disruption - unstable Coronary Artery disease
Thrombosis - very unstable
Thrombolysis - dissolution of blood clot

Can continue to downstream embolism

Question 9

Role of Anti-platelet drugs and how they act?

Answer 9

To limit growth of, or decrease risk of, arterial Thrombosis

Act by inhibiting platelet aggregation

Question 10

Main indication for Anti-platelet drugs

Answer 10

•primary prevention of Atherothrombotic events in people who are high risk (only considered in people at high risk of stroke or MI)

•secondary prevention of CV events in people with ACS, angina, PAD
>after MI, Stent implantation, stroke or TIA

•prevention of Atherothrombotic events in people undergoing PCI

(Remember the instance of bleeding of these drugs is v.high - can lead to death. So benefit vs risk…)