SACCM 165: Anticoagulants

Question 1

What are the antithrombotic properties of the endothelium?

Answer 1

• provides a negatively charged surface –> repells platelet attachement
• TFPI localized on the endothelial surface
• endothelial cells produce and secrete vasodilatory and antithrombotic substances (NO2, prostacycline/PGI2, ecto-ADPase)
• physical barrier between vWF, collagen, fibroblasts, TF, and plasma

Question 2

Per the CURATIVE guidelines, what are considered conditions with high risk of clot formation in dogs and cats?

Answer 2

• dogs: PLN and IMHA
• cats: cardiomyopathy with LA enlargement or low blood flow velocity within LA

Question 3

Explain the mechanism of action of Warfarin

Answer 3

• inhibits Vitamin K recycling
• blocks Vitamin K epoxide reductase
• when active Vitamin K is used for carboxylation of FII, FVII, FIX, FX, Protein C and S -> Vitamin K changed to its inactive form Epoxide Vitamin K and needs to be converted by vitamin K epoxide reductase to quinone and by vitamin K reductase to Hydroquinone vitamin K

Question 4

Why is heparin initially administered in people receiving warfarin?

Answer 4

initial prothrombotic phase because of less Protein C and S

Question 5

Where is bleeding from warfarin therapy usually observed?

Answer 5

GI tract, urinary tract, less commonly pulmonary or intracranially

Question 6

How do you calculate the international normalized ratio?

Answer 6

[PT patient/ PT reference median]^international sensitivity index

Question 7

What is the INR goal when administering warfarin?

Answer 7

2.0-4.0

Question 8

What molecular weight range does unfrationated heparin have?

Answer 8

5,000-30,000 Da

Question 9

What factors are inactivated by unfractionated heparin?

Answer 9

indirectly: FIIa, FXa, FIXa, FXIa, FXIIa

Question 10

besides clotting factor inactivation how does unfractionated heparin exert antithrombotic effects?

Answer 10

stimulates TFPI release from the endothelial cell surface

Question 11

How do you reverse heparin?

Answer 11

protamine sulfate

Question 12

Why is the bioavailability of unfractionated heparin more unpredictable than that of LMWH?

Answer 12

UFH binds to surface of endothelial cells, macrophages, and platelelts and is highly protein bound –> alters availability of UFH
LMWH is not as protein or cell surface bound

Question 13

What may reduce the efficacy of heparin in sepsis?

Answer 13

sepsis has been associated with decreased levels of antithrombin –> needed for effect of heparin

Question 14

At what ratio does LMWH inhibit FIIa and FXa?

Answer 14

1:4

Question 15

What is the average molecular weight of LMWH?

Answer 15

~ 5,000 Da

Question 16

How effective is Protamine sulfate in reversing the effects of LMWH?

Answer 16

can only reverse some anticoagulant activity, -> anti-FXa not completelet neutralized

Question 17

Why do you may have to adjust dosing of LMWH in animals with kidney failure?

Answer 17

LMWH extreted via kidneys

Question 18

What is the aPTT goal when giving heparin?

Answer 18

1.5-2.0

Question 19

What is the anti-Xa activity goal when treating with UFH or LMWH?

Answer 19

0.35-0.7 U/mL UFH
0.5-1.0 U/mL LMWH

Question 20

What condition may require higher dosages of UFH?

Answer 20

IMHA

Question 21

What type of drugs are Argatroban, Dabigatran, Lepirudin, or Ximelagatran?

Answer 21

Direct thrombin inhibitors

Question 22

At what time after administration does Rivaroxaban exert the most anticoagulant effects, how long do effects last?

Answer 22

3 hours after administration, lasting 24 hours