AntiCoagulants and Other drugs Flashcards
Aspirin MOA, AE, evidence, and monitoring
MOA - reduces plt production of TXA2 via the arachidonic acid metabolism pathway through irreversible binding to COX (non selective)
Variable patient absorption and efficacy reported
AEs mostly GI but also bleeding risk and renal damage
Most recent publications suggest efficacy of newer anti-plt drugs is better based on aggregometry which has also been demonstrated to be inferior to clopidogrel in FATE prevention/recurrence in FATCAT study
Platelet aggregometry may be best monitoring means but so far has been found to be insensitive. Other signs of GI upset and monitoring of renal and liver values also indicated
Clopidogrel MOA, AE, evidence, and monitoring
MOA = binds to PY2 receptor on platelet preventing ADP activation and subsequent aggregation. It is a prodrug converted to active metabolite in liver.
Variable individual pharmacokinetics in dogs and cats may account for some non-responders in studies. Though concentration of active metabolite in serum was not predictive of platelet inhibition in one study.
AE- rarely reported but may be GI (reduced if given with food) or bleeding if used in dual therapy
Monitoring - no specific monitoring recommended, though plt aggregometry has some evidence of ability to detect action. Tx and Dz specific targets are lacking. Overall low risk but difficult to know if effective dose.
2 studies have shown synergistic effect when combined with rivaroxaban. I retrospective case series reported reduced recurrence of FATE and PFI in FATE cats. Another reported the synergistic effects on platelet aggregation inhibition in healthy cats where platelet aggregation in response to different agonists was measured.
Heparin (UFH and LMWH) MOA, AE, evidence, and monitoring
MOA - promotion of anti-coagulant proteins in particular antithrombin but also inhibition of F10a thus resulting in reduced thrombin production (a procoagulant)
Also UFH inhibits F13 which cross links fibrin
LMWH (enoxaparin) more specifically inhibits the F10a
AEs - bleeding risk, needs close monitoring. May be reeduced risk in LMWH
Enoxaparin was shown to reduce anti-Xa activity in cats given a single injection (healthy cats)
No direct comparison of UFH and LMWH - but improved safety profile of the latter may promotes its use (and lab studies suggested non-inferior).
Studies of UFH in IMHA have conflicting results of efficacy in prevention of thrombosis.
Monitoring - anti-factor Xa activity ios more reliable than PT/APTT for monitoring efficacy. Though availability is limited in Aus/NZ. Tx and Dz specific target suppression are not published. Though there are conensus guidelines in JVECCS CURATIVE domain. Recommended to measure at peak anti-coagulant activity time (3-4h post dosing
Rivaroxaban MOA, AE, evidence, and monitoring
MOA - direct inhibition of F10a, no cofactor needed
AE - low reported rates of bleeding or other signs. May have increased risk in dual agent therapy
Evidence - as with clopidogrel 2 studies in JFMS reporting its benefit in FATE when combined with clopidogrel.
A small study in 19 dogs with thrombotic disease showed variable serum levels of drug not correlated with dose. Though effect on haemostasis was not evaluated
Monitoring - measurement of drug level available in US. Best done 3-4h after Tx. Target levels are not established but could use to ensure adequate theoretical dosing. Could also look at Anti-Xa activity.
A recent JVIM study demonstrated TEG was also able to detect therapeutic anti-Xa concentrations using tissue factor agonists.
Warfarin - MOA, AE, evidence, and monitoring
MOA - Vit K reductase inhibitor, reducing functional clotting factors.
AEs - high risk of bleeding and GI upset
Evidence - low evidence for efficacy in dog or cat hypercoagulable disease and narrow therapeutic window so not recommended over other options
tPA MOA, AE, evidence, and monitoring
tPA is a synthetic plasminogen activator used to promote thrombolysis in patients presenting acutely. Needs to be used in the early stages of clot development to be effective.
AEs - reperfusion injury, hyperfibrinolysis, hypocoagulability
Evidence - lacking, 2 studies recently in cats found no improvement in survival in treatment of FATE compared to standard of care. one prospective and one retrospective. Though high mortality in this disease makes calculation of statistically significant benefit challenging.
Tranexamic acid - MOA, AE, evidence, and monitoring
MOA - prevention or treatment of post-operative haemorrhage due to fibrinolysis. Or diseases known to cause hyperfibrinolysis
Inhibits fibrin b/d by binding to plasminogen and preventing its binding to fibrin -> stabilisation of clot matrix
AEs - GI upset, emesis can be induced by rapid injection. Seizures reported with IV use in dogs. Thrombosis/TE have been reported with IV use in humans. Ureteral obstruction with clots in patients with renal haematuria
Evidence - minimal in greyhounds with haemorrhage. Prophylactic use has limited/no evidence. post-op use may reduce occurrence based on efficacy reported for EACA in GHs undergoing amputation or neutering.
How do glucocorticoids contribute to hypercoagulability (drugs and endogenous)
Promote hypertension through Na/water retention and vasoconstriction
Cause proteinuria which may deplete antithrombin or other anticoagulant factor loss
Reduced hepatic clearance of clotting factors
Increase blood viscosity by promotion of erythropoiesis and secondary dehydration
Increased fibrinogen
May cause lethargy - blood stasis
