Antiplatelets

Question 1

Difference between a thrombus and an embolus

Answer 1

Thrombus - clot adhered to a vessel wall

Embolus - intravascular clot distal to site of origin

Question 2

Difference between venous and arterial thrombosis

Answer 2

VT - associated with stasis of blood/ damage to veins
High RBC & fibrin content
Low platelet content evenly distributed

AT - usually at site of atherosclerosis following plaque rupture
Lower fibrin content
Much higher platelet content

Question 3

How does normal healthy endothelium help to prevent platelet aggregation?

Answer 3

Endothelial cells ->

prostacyclin (PGI2) ->

platelet receptor ->

⬆️cAMP in platelets ->

⬇️Ca2+
(prevents aggregation - decrease in agents, stabilises GP2b/3a receptors)

Question 4

Explain the process of platelet aggregation

Answer 4

Platelet adhesion:
Activated platelets adhere exposed subendothelial surface damaged endothelium

Platelet activation:
Activated platelets -> chemical mediators (Thromboxane A2, ADP, serotonin, Platelet activation factor, thrombin) ->
⬆️ca2+ -> release platelet granules, activation thromboxane A2 synthesis, activation GP 2b/2a receptors

Platelet aggregation:
Platelets recruited into plug by fibrinogen binding to GP2a/ 3b receptors on platelets

Question 5

What do antiplatelet and fibrinolytic drugs target?

Answer 5

Target platelet rich white arterial thrombi

Question 6

What targets lower platelet content, red venous thrombi?

Answer 6

Parenteral anticoagulants (e.g. heparins) and 
Oral anticoagulants (e.g. warfarin)

Question 7

When is a combination of antiplatelet, fibrinolytics and anticoagulants used?

Answer 7

Some patients

Often in secondary prevention

Question 8

What is a

cyclo-oxygenase inhibitor, give an example, side effects, drug cautions?

Answer 8

Potent platelet aggregating agent thromboxane A2 formed from arachidonic acid by COX-1
- inhibit CoX-1 to stop synthesis
Higher doses inhibit PGI2

E.g. Aspirin (at low non-analgesic doses)

Irreversible - lasts lifespan of platelet (7-10days)

❌bleeding time prolonged (stroke, GI bleeding - peptic ulcer), Reye’s syndrome (hepatic issues, oedema) - avoid <16yrs, hypersensitivity, 3rd trimester - premature closure ductus arteriosus

Other antiplatelets + anticoagulants additive/ synergistic action

Question 9

Why does aspirin not work as well in some people?

Answer 9

COX-1 polymorphism result in lack of efficacy in some

Question 10

When do we use aspirin?

Answer 10

Secondary prevention:
Stroke
TIA
Acute coronary syndrome 
MI in stable angina/ peripheral vascular disease

Post primary percutaneous coronary intervention (mechanical stent & cleaning out of clot)

Gastric protection - reduces prostaglandins

Question 11

What is an ADP receptor antagonist? Give examples and the differences between them

Answer 11

Inhibits binding of ADP to P2Y12 receptor so inhibits activation of GP2b/ 3a receptors

E.g. clopidogrel (slow onset, individual variability in action), prasugrel & * (both more rapid 1-2hr onset) - irreversible , prodrugs - hepatic metabolism

*ticagrelor - reversible, at different isle (active metabolites)

Question 12

Side effects of ADP receptor antagonists and drug cautions

Answer 12

❌ bleeding (GI upset- dyspepsia, diarrhoea, thrombocytopenia), renal and hepatic impairment

Clopidogrel requires CYPs for activation (omeprazole, ciprofloxacin, erythromycin, SSRIs inhibitors) - needs stooping 7 days prior surgery

Ticagrelor can interact with CYP inhibitors and inducers - stopping 5 days prior surgery

Caution with NSAIS/ other anticoagulants/ antiplatelets

Question 13

When do we use ADP receptor antagonists?

Answer 13

Clopidogrel - mono therapy where aspirin contraindicated
NSTEMI for up to 12 months

STEmI with stent up to 12m

Secondary or Venetian:
Ischaemic stroke
TIA

Prasugrel with aspirin in ACS undergoing PCI up to 12 months

Ticagrelor + aspirin prevent atherothrombotic events in ACs up to 12months

Question 14

What are glycoprotein 2b/ 3a inhibitors, give an example?

Answer 14

Block binding of fibrinogen and Von willebrand factor - final common pathway - more complete platelet aggregation

E.g. Abciximab - antibody blocks receptors >80% reduction in aggregation

Given IV with bolus

Question 15

Side effects and cautions with glycoprotein 2b/3a inhibitors, main use

Answer 15

❌bleeding! Thrombocytopenia, hypotension, bradycardia

• other antiplatelets + anticoagulants
• use in high risk percutaneous transluminal coronary angioplasty patients

Question 16

How does dipyridamole work? Side effects, cautions, uses

Answer 16

phosphodiester inhibitor -> prevents cAMP degradation -> inhibits expression of GP2b/ 3a

Main action: Inhibits cellular reuptake of adenosine -> increases plasma adenosine -> inhibits platelet aggregation via A2 receptors

❌ flushing, headaches, hypersensitivity

Caution antihypertensives, antiplatelets, anticoagulants

Uses:
Secondary prevention stroke/ TIA
Prophylaxis of thromboembolism following valve replacement

Question 17

What are fibrinolytic agents (thrombolysis) or clot busters? Give two and how they work together. What inhibits their action? When are they used? Side effect

Answer 17

Fibrinolytics dissolve fibrin meshwork of thrombus

E.g. streptokinase (from streptococci, only given once then body develops antibodies)

Streptokinase -> plasminogen (plasminogen activators e.g. alteplase) -> plasmin -> fibrinolysis (tranexamic acid inhibits)

Uses:
Alteplase in acute ischaemic stroke <4.5hrs, following AMI diagnosis vs primary PCI

❌bleeding, Intracranial haemorrhage

Question 18

What should you offer someone with acute STEMI if presentation within 12hrs of onset symptoms and primary percutaneous coronary intervention can be delivered within 120minutes of the time when fibrinolysis could have been given?

Answer 18

Offer coronary angiography with follow on primary PCI if indicated as the preferred coronary repercussions strategy

ACEi should be offered to all post Mi once haemodynamically stable

‘Dead meat don’t beat’
Slide 20 - need to reperfuse