Anti-Thrombotics

Question 1

What two tests can measure the effectiveness of the antiplatelet drugs?

Answer 1

1. Platelet Aggregation Assay/aggregometry

2. Bleeding Time Test

Question 2

What tests can be used to measure the effectiveness of

1. Warfarin
2. unfractionated Heparin
3. LMWH

Answer 2

1. PT with INR
2. aPTT
3. Factor Xa inhibition assay

Question 3

Name the 3 Thienopyridines and the MOA.

Answer 3

1. Ticlopidine
2. Clopidogrel
3. Prasugrel

MOA: inhibit ADP receptors on platelets preventing platelet activation

Question 4

Name the two major side effects of Thienopyridines and which of the 3 drugs is the worst culprit.

Answer 4

1. Severe Neutropenia
2. Thrombotic Thrombocytopenic Purpura (TTP)

Ticlopidine

Question 5

What is important to remember about the metabolism of clipidogrel?

Answer 5

It is a pro-drug metabolized by CYP2C19. A significant number of the population has a genetic mutation in this enzyme and the drug is ineffective.

Question 6

What are 3 contraindications for Prasugrel?

Answer 6

Older than 75
Hx of TIA or CVA
Weight less than 60kg

Question 7

What is the only Non-thienopyridine drug and its MOA?

Answer 7

Ticagrelor

MOA: reversibly binds ADP receptors on platelets preventing activation

Question 8

Name the 3 GPIIb/IIIa inhibitors and the MOA.

Answer 8

1. Abciximab
2. Eptifibitide
3. Tirofiban

Block GPIIb/IIIa receptors preventing platelet aggregation

Question 9

Which GPIIb/IIIa inhibitor is known for causing most severe thrombocytopenia?

Answer 9

Abciximab

Question 10

MOA and main use for Dipyridamole.

Answer 10

MOA: lowers platelet intracellular cAMP levels, dropping Ca2+ levels preventing platelet activation.

Not very effective alone, used to enhance other anti-thrombotics

Question 11

MOA and use for Cilostazol

Answer 11

MOA: Phosphodiesterase inhibitor causing vasodilation leading to prevention of platelet aggregation.

Used to treat ambulatory claudication seen in peripheral arterial disease

Question 12

MOA of Warfarin

Answer 12

Inhibits Vit. K epoxide reductase.

The reduced form of Vit. K is needed to make clotting factors II, VII, IX, and X

Question 13

What is a paradoxical side effect of warfarin use?

Answer 13

Hypercoagulable state.
Vitamin K is also necessary for production of Protein C. Protein C is activated by thrombomodulin-thrombin complex. Once activated, C combines with Protein S and the complex inactivates Factor Va and Factor VIIIa inhibiting the clotting cascade.

Without protein C there is less inhibition of the clotting cascade increasing the risk for thrombus formation. The liver also responds by initiating increased clotting factor production. So warfarin should not be started without heparin or some other anticoagulant along with it.

Question 14

What is the bleeding management for a patient on warfarin?

Answer 14

1. Stop warfarin use
2. Give Vit. K
3. Emergent cases: transfuse fresh plasma

Question 15

MOA of unfractionated heparin.

Answer 15

Combine with Antithrombin III forming a ternary complex (very stable 3 subunit complex) increasing its activity. It breaks up thrombin and activated Factor X (Factor Xa).

Question 16

MOA of LMWH

Answer 16

Combine with Antithrombin III (but with less stability due to smaller size) only inactivating factor Xa.

Question 17

Disdavantage of LMWH use.

Answer 17

Dose reduction necessary in renal insufficiency.

Question 18

Antidote for emergent bleeding due to heparin use.

Answer 18

Protamine Sulfate
(does not fix HIT, just the bleeding)

Question 19

Describe the two types of HIT.

Answer 19

Non-immune mediated Heparin induced Thrombocytopenia:
-prolonged use (or too high of dose) leads to decreased amounts of platelets, benign condition

Immune-Mediated HIT
-use of Heparin causes the formation of “anti-heparin” antibodies that activates platelets leading to a hypercoagulable state and small vessel thrombus formation

Question 20

What is management for Immune-mediated HIT?

Answer 20

Stop Heparin Use

Start patient on Direct Thrombin Inhibitors

Question 21

Name the 4 direct thrombin inhibitors.

Answer 21

1. Lepirudin
2. Bivalrudin
3. Argatroban
4. Dabigatran

Question 22

Only indication for Direct thrombin inhibitors in anticoagulation.

Answer 22

Treatment of HIT or for patients with a Hx of HIT.
(Dabigatran is also used in place of warfarin to reduce stroke and systemic embolus risk without increased bleeding risk)

Question 23

What are the two warning of Dabigatran use?

Answer 23

1. Don’t use in patients with renal insufficiency.

2. Discontinuing use requires alternative anticoagulants to prevent rebound clotting (leading to stroke, MI etc.)

Question 24

Drug used for DVT treatment and DVT prophylaxis in hip and knee ortho surgery.

Answer 24

Fondaparinux

Xa inhibitor

Question 25

Drug used in DVT prophylaxis during hip and knee ortho surgery but needs dose reduction in renal insufficiency.

Answer 25

Rivaroxaban

Xa inhibitor

Question 26

Drug used to reduce risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, but dose reduction necessary in renal insufficiency.

Answer 26

Apixaban

Xa inhibitor

Question 27

Which two Xa inhibitors require an alternative anticoagulant if they are discontinued to prevent risk of thrombotic events?

Answer 27

Rivaroxaban

Apixaban

Question 28

Name the drugs that require adjusted dosing for renal insufficiency. (4-ish)

Answer 28

1. LMWH (“-parins”)
2. Dabigatran
3. Rivaroxaban
4. Apixaban