Anticoagulants

Question 1

What is the MOA of the oral anticoagulant warfarin?

Answer 1

inhibits the hepatic synthesis of Vit K dependent clotting factors II, VII, IX, and X via inhibition of vitamin K epoxide reductase

Question 2

What is the MOA of heparin?

Answer 2

catalyzes the binding of antithrombin III ( a serine protease inhibitor) to factors IIa, IXa, Xa, XIa, and XIIa resulting in their rapid inactivation; therefore inhibiting activity of several activated clotting factors.

Question 3

What is the purpose of protein C and protein S in the body?

Answer 3

to cause proteolysis of factors Va and VIIIa (endogenous anticoagulants)

Question 4

Compare and contrast the chemical nature of heparin to warfarin?

Answer 4

Heparin is a large polysaccharide that is water soluble; whereas

warfarin is a small molecule that is lipid soluble

Question 5

PTT meaning?

Answer 5

partial thromboplastin time

Question 6

PT meaning?

Answer 6

prothrombin time

Question 7

Heparin is monitored using PT or PTT? Which pathway extrinsic or intrinsic?

Answer 7

PTT (intrinsic)

Question 8

What is the antidote for heparin use?

Answer 8

protamine sulfate - chemical antagonism, fast onset

Question 9

What is the antidote for warfarin?

Answer 9

Vit. K inc. cofactor synthesis (slow onset)
fresh frozen plasma (fast)

Question 10

What are the uses for heparin?

Answer 10

rapid anticoagulation (intensive) for thromboses,
emboli,
unstable angina
DIC
open-heart surgery

Question 11

What are the uses for warfarin?

Answer 11

longer-term anticoagulation (controlled) for thromboses,
emboli
post-MI,
heart valve damage,
atrial arrythmias
etc

Question 12

What are some toxicities associated with heparin use?

Answer 12

bleeding
osteoporosis
heparin-induced thrombocytopenia (HIT),
HSR

Question 13

What are some toxicities associated with warfarin use?

Answer 13

bleeding
skin necrosis (if low protein C)
drug interactions
teratogenic (bone dysmorphogenesis)

Question 14

What are some potential advantages of using low-molecular weight heparins?

Answer 14

have longer half-life,
less thrombocytopenia,
possible enhanced activity against factor Xa

Question 15

What is normal PT time?

Answer 15

10-14 s

Question 16

What is normal INR range?

Answer 16

0.8 - 1.2 (think around 1)

Question 17

What is a safe range for the INR (international normalized ratio) to go up to when a patient is on warfarin?

Answer 17

around 2 - 2.5

Question 18

How can warfarin lead to protein C deficiency and hyper-coagualable states?

Answer 18

Has a short half life so transient deficiency will occur

Vit. C is endogenous anticoagulant so other coagulation factors are in high amounts with unopposed action

Question 19

What is the MOA of direct thrombin inhibitors?

Answer 19

To directly inhibit thrombin and does not require antithrombin III

Directly inhibits IIa

Question 20

Name a LMW heparin?

Answer 20

enoxaparin

Question 21

Name some direct thrombin inhibitors.

Answer 21

Argatroban
Dabigatran
Bivalirudin

Question 22

Indication for argatroban?

Answer 22

used in HIT

Question 23

Which direct thrombin inhibitor does not require monitoring of PT or INR?

Answer 23

dabigatran

Question 24

Indication for dabigatran?

Answer 24

a fib as an alternative to warfarin

Question 25

What is the antidote for use of dabigatran?

Answer 25

idarucizumab

Question 26

Bivalirudin Indication.

Answer 26

used with aspirin in unstable angina when undergoing percutaneous transluminal coronary angioplasty (PTCA)

Question 27

Name the direct factor Xa inhibitors. What is the suffix to remember them?

Answer 27

“-xabans”
(has xa in name)

Rivaroxaban

Question 28

Do factor Xa inhibitors require monitoring of PT or INR?

Answer 28

no

Question 29

Indications for the direct factor Xa inhibitors?

Answer 29

Used to prevent DVTs after knee/hip surgery;
prevention of stroke
systemic embolism in non-valvular atrial fibrillation

Question 30

Antidote for the direct factor Xa inhibitors.

Answer 30

rapidly reversed by andexanet alfa

(also has xa in name) Xa net