Thromboembolism prophylaxis Flashcards
What disease predispose animal to thromboembolism?
hypertrophic cardiomyopathy due to abnormal blood flow
Mechanism of action of clopidogrel
- 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
Clinical usage of Clopidogrel
- prophylaxis against possible thromboembolism
- adjunct in IMHA in dogs
Effect of Clopidogrel comparing to Aspirin
- better than aspirin to prevent recurrence of thromboembolism in cats
- inhibits platelet aggregation via another mechanism
- safer than aspirin
What can we do with Clopidogrel in severe cases of thromboembolism?
combine with aspirin (different mechanisms of action)
How effective are Clopidogrel in cats?
varies between individual cats
How are Clopidogrel metabolized?
by hepatic P450 enzymes to active metabolite
How are Clopidogrel excreted?
bile & urine
Adverse effects of Clopidogrel
- Occasionally GI irritation in cats
Mechanism of action for aspirin
- 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
How is aspirin metabolized?
- glucuronidation primarily ( slow & can accumulate in cats)
Adverse effects of aspirin
- GI irritation, bleeding, acidosis
- renal decompensation
- dose-dependent increase in prothrombin time
What can increase the chance of adverse effect with aspirin?
decreased renal or hepatic function
Contraindication of aspirin
NSAIDs or glucocorticoid usage
Heparin function
- anticoagulant
- suppression of thrombin-dependent amplification of the coagulation cascade & inhibition of thrombin-mediated conversion of fibrinogen to fibrin
Mechanism of action for heparin
- binds to antithrombin III and converts it to potent inhibitor serine proteases
- serine protease inhibits several coagulation factors
Indications for heparin
treatment for DIC, IMHA patient
What needs to be done when using heparin?
- frequent monitoring of PTT
- ensure that the effects are not too pronounced (want up to 1.5-2x the PTT)
The 2 types of heparin available
- unfractioned
- low molecular weight heparin
What is unfractionated heparin
- 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
What is low molecular weight heparin?
- 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
Adverse effects of heparin
hemorrhage, local pain, erythema, hematoma at injection site
