Coagluation

Question 1

What is the mechanism of action of heparin?

Answer 1

activating antithrombin III (ATIII)
accelerating the rate at which antithrombin inhibits thrombin (factor IIa) and factor Xa

1g protamine reverses 100U of heparin
Monitor aPTT

Question 2

What is the mechanism of HIT type II?

Answer 2

immune-mediated
antibodies (IgG) against complex of platelet factor 4 (PF4) and heparin
5–14 days

Question 3

What is the mechanism of action of LMWH (eg.enoxaparin, dalteparin) ?

Answer 3

activating AT III –> inhibiting factor Xa
little effect on thrombin inhibition

Protamine incompletely reverses

Question 4

Is the risk of HIT higher or lower with LMWH compared to heparin?

Answer 4

fivefold lower with LMWH than with heparin due to its lower affinity for PF4

LMWH should NOT be used to anti-coagulate HIT patients because most HIT antibodies exhibit cross-reactivity with LMWH

Question 5

What is the mechanism of action of fondaparinux?

Answer 5

factor Xa inhibition

cleared unchanged in the kidneys, it is contraindicated in patients with renal insufficiency

Question 6

What is the mechanism of argatroban?

Answer 6

synthetic direct thrombin inhibitor

Question 7

List the direct thrombin inhibitors and how do you monitor their effects?

Answer 7

argatroban
dagibitran
lepirudin
bivalrudin

Monitor = aPTT

Question 8

What is the mechanism of action of warfarin?

Answer 8

interferes with the synthesis of the vitamin K–dependent clotting proteins, which include factors II, VII, IX, and X and protein C and S

Question 9

How is warfarin’s anticoagulant effect monitored?

Answer 9

prothrombin time (PT) or INR

Question 10

What is the mechanism of action of dabigatran?

Answer 10

oral direct thrombin inhibitor

Question 11

Is there an antidote for the oral factor Xa inhibitors?

Answer 11

No

Question 12

What is the mechanism of action and side effects of aspirin?

Answer 12

irreversible inhibition of cyclooxygenase 1 and 2 (COX-1 and COX-2)

antithrombotic effect = primarily inhibition of COX-1 on platelets

SE = dyspepsia, peptic ulcers with bleeding and perforation

Question 13

What is the mechanism of action of dipyridamole?

Answer 13

inhibiting phosphodiesterase –> blocks breakdown of cyclic adenosine monophosphate (cAMP) –> Increased levels of cAMP reduce intracellular calcium and inhibit platelet activation

Question 14

Name 3 platelet ADP receptor antagonists.

Answer 14

ticlopidine
clopidogrel
prasugrel
ticagrelor

Question 15

Name 3 platelet Gp IIb/IIIa receptor inhibitors.

Answer 15

abciximab - long half-life
eptifibatide
tirofiban

Question 16

List some drugs that decease warfarin’s effects

Answer 16

barbiturates
carbamazepine
cholestyramine
nafcillin
phenobarbital
phenytoin
rifampin

Question 17

List some drugs that increase warfarin’s effects

Answer 17

Levofloxacin
omeprazole
amiodarone

Question 18

What are the mechanisms of action for oral anti-platelet agents?

Answer 18

ASA - COX2 inhibitor
Dipyrimadole - PDE inhibitor
ADP inhibitors - block P2Y12 receptor on platelets

Question 19

What drugs can be used w/ a history of HIT type-II?

Answer 19

fondaparinux
argatroban
bilavrudin

Question 20

Explain the mechanism of action of un-fractioned Heparin.

Answer 20

binding to Antithrombin III (ATIII) and accelerating its activity by 100-1000 times

The ATIII-heparin complex primarily inhibits thrombin (Factor IIa) and factor Xa

Question 21

What are the 3 types of protamine reactions?

Answer 21

Systemic hypotension from histamine release

Anaphylactic reaction (IgE Mediated)

Severe pulmonary hypertension and right ventricular failure - IgG mediated immune reaction - more common in patients with fish allergy, previous vasectomy, or prior exposure to protamine or NPH insulin.

Question 22

Describe an advantage and a disadvantage of bivalirudin and argatroban to heparin.

Answer 22

Unlike heparin, bivalirudin and argatroban can be used in HIT patients, but they have no antidote to reverse their effects.

Question 23

Compare the mechanism of action of Rivaroxaban (Xarelto) and Dabigatran (Pradaxa)?

Answer 23

Rivaroxaban (Xarelto) is a direct factor Xa inhibitor

Dabigatran (Pradaxa) is a direct thrombin inhibitor