Thromboembolism prophylaxis

Question 1

What disease predispose animal to thromboembolism?

Answer 1

hypertrophic cardiomyopathy due to abnormal blood flow

Question 2

Mechanism of action of clopidogrel

Answer 2

• platelet aggregation antagonist
• prodrug; active metabolite is an irreversible ADP antagonist
• inhibit binding of ADP to platelet receptor to prevent ADP-mediated platelet aggregation
• lasts for the duration of the platelet’s life span

Question 3

Clinical usage of Clopidogrel

Answer 3

• prophylaxis against possible thromboembolism
• adjunct in IMHA in dogs

Question 4

Effect of Clopidogrel comparing to Aspirin

Answer 4

• better than aspirin to prevent recurrence of thromboembolism in cats
• inhibits platelet aggregation via another mechanism
• safer than aspirin

Question 5

What can we do with Clopidogrel in severe cases of thromboembolism?

Answer 5

combine with aspirin (different mechanisms of action)

Question 6

How effective are Clopidogrel in cats?

Answer 6

varies between individual cats

Question 7

How are Clopidogrel metabolized?

Answer 7

by hepatic P450 enzymes to active metabolite

Question 8

How are Clopidogrel excreted?

Answer 8

bile & urine

Question 9

Adverse effects of Clopidogrel

Answer 9

• Occasionally GI irritation in cats

Question 10

Mechanism of action for aspirin

Answer 10

• irreversible inhibition of COX-1 by acetylation
• decrease platelet synthesis of thromboxane ( released from platelet storage to stimulate aggregation)
• for the duration of platelet life span

Question 11

How is aspirin metabolized?

Answer 11

• glucuronidation primarily ( slow & can accumulate in cats)

Question 12

Adverse effects of aspirin

Answer 12

• GI irritation, bleeding, acidosis
• renal decompensation
• dose-dependent increase in prothrombin time

Question 13

What can increase the chance of adverse effect with aspirin?

Answer 13

decreased renal or hepatic function

Question 14

Contraindication of aspirin

Answer 14

NSAIDs or glucocorticoid usage

Question 15

Heparin function

Answer 15

• anticoagulant
• suppression of thrombin-dependent amplification of the coagulation cascade & inhibition of thrombin-mediated conversion of fibrinogen to fibrin

Question 16

Mechanism of action for heparin

Answer 16

• binds to antithrombin III and converts it to potent inhibitor serine proteases
• serine protease inhibits several coagulation factors

Question 17

Indications for heparin

Answer 17

treatment for DIC, IMHA patient

Question 18

What needs to be done when using heparin?

Answer 18

• frequent monitoring of PTT
• ensure that the effects are not too pronounced (want up to 1.5-2x the PTT)

Question 19

The 2 types of heparin available

Answer 19

1. unfractioned
2. low molecular weight heparin

Question 20

What is unfractionated heparin

Answer 20

• variable lengths of molecular chains
• binds to antithrombin III and inhibits both thrombin & factor X
• unpredictable anticoagulant effects
• binds to numerous plasma proteins & endothelial cells

Question 21

What is low molecular weight heparin?

Answer 21

• contains only smaller molecular chains
• more bioavailable
• binds to antithrombin III and only stimulates inhibition of factor Xa
• more subtle with fewer adverse effects
• binds poorly to plasma protein
• cleared through kidneys

Question 22

Adverse effects of heparin

Answer 22

hemorrhage, local pain, erythema, hematoma at injection site