Antiplatelets and Anticoagulation

Question 1

What is haemostasis?

Answer 1

Attempt to stop blood loss from a site of injury

Question 2

Describe the stages of haemostasis?

Answer 2

1) Vascular wall damage exposing collagen and tissue factor (TF)
2) Primary haemostasis => platelet adhesion
3) Activation of coagulation cascade and the formation of a stable clot

Question 3

When platelets bind and become activated in Primary Haemostasis, what do they release?

Answer 3

Thromboxane A2 (TXA2)

Question 4

How does TXA2 aid in primary haemostasis?

Answer 4

• stimulates 5HT (serotonin) release to vasoconstrict blood vessels
• stimulates ADP release to gather other platelets to the site

Question 5

What is meant by thrombosis?

Answer 5

Thrombosis

• pathological haemostasis
• a haematological plug in the absence of bleeding

Question 6

What factors predispose a patient to thrombosis?

Answer 6

Virchow’s triad:

• injury to vessel wall
• abnormal blood flow
• increased coagulability of the blood

Question 7

Describe the difference between an arterial and venous thrombus and how each of these are treated

Answer 7

Arterial thrombus:
- white, platelet rich thrombus
=> Tx = antiplatelets

Venous thrombus:
- red fibrin rich thrombus
=> Tx = anticoagulants

Question 8

When are anticoagulants used?

Answer 8

• deep vein thrombosis (DVT)
• prevention of post-operative thrombosis
• patients with artificial heart valves
• atrial fibrillation

Question 9

Warfarin inhibits which clotting factors?

Answer 9

Factors II, VII, IX, X

Question 10

Warfarin has a slow onset (2-3 days) and a long half life.What drug can be used for a more rapid effect?

Answer 10

Heparin

Question 11

What factors can potentiate warfarin action (i.e. increase a patient’s risk of haemorrhage)?

Answer 11

• liver disease – decreased clotting factors
• high metabolic rate – increased clearance of clotting factors

Drug interactions:

• agents that inhibit hepatic metabolism of warfarin by CYP2C9
• drugs that inhibit platelet function (e.g. aspirin, other NSAIDs)
• drugs that decrease availability of vitamin K

Question 12

What factors can lessen the action of warfarin (i.e. make the patient more likely to clot)?

Answer 12

• physiological state – pregnancy
• hypothyroidism (decreased degradation of clotting factors)
• high vitamin K consumption

Drug interaction:
- agents that increase hepatic metabolism of warfarin

Question 13

How is Heparin given?

Answer 13

Heparin is administered either IV (immediate onset) or SC (onset delayed by 1 hour)

LMWHs are given SC

Question 14

Why are LMW Heparins not used in renal failure?

Answer 14

They are renally excreted

=> if patient cant excrete them properly they may be at higher bleeding risk

Question 15

What are the adverse effects of heparin and LMWH?

Answer 15

• haemorrhage
• osteoporosis (long term treatment)
• hypoaldosteronism
• hypersensitivity reactions

Question 16

What antidote is given if a patient haemorrhages on heparin?

Answer 16

protamine sulfate IV (inactivates heparin)

Question 17

What is the only pitfall of the New Oral Anticoagulant drugs?

Answer 17

• No specific agent is available to reduce haemorrhage in overdose (i.e. no antidote)

Question 18

What do antiplatelet drugs block in order to prevent clotting?

Answer 18

Aspirin - Blocks COX2 enzyme, this is involved in making TXA2

Clopidogral blocks ADP

Question 19

How long before an operation should aspirin be stopped?

Answer 19

• 1 week

- TXA2 synthesis does not recover until affected platelets are replaced (7-10 days)

Question 20

What are the main adverse effects of aspirin?

Answer 20

gastrointestinal bleeding and ulceration

contraindicated for patients <16 years (Reyes syndrome) and for asthmatic patients

Question 21

When are fibrinolytic drugs used?

Answer 21

• to reopen occluded arteries in acute MI or stroke –

- Administered IV within as short a period as possible of the event

Question 22

Give examples of fibrinolytic drugs

Answer 22

Streptokinase

• Reduces mortality MI
• IV or intracoronary

Alteplase and duteplase

• tissue plasminogen activator (rt-PA)
• Short half life, hence given by IV infusion

Question 23

Further streptokinase doses should not be given how long after the first dose?

Answer 23

• 4 days

- action blocked by the generation of antibodies

Question 24

The major adverse effects of fibrinolytics is haemorrhage. How is this controlled?

Answer 24

• oral tranexamic acid given
• This inhibits plasminogen activation
• plasminogen pathway is targeted by the fibrinolytic drugs