Antithrombotics + Anticoagulants

Question 1

What is hemostasis?

Answer 1

The process of stopping blood loss from injured vessels

Question 2

How is a hemostatic plug formed and stabilized?

Answer 2

It is formed by aggregated platelets and then stabilized by cross-linked fibres

Question 3

What is thrombosis?

Answer 3

Unwanted formation of a hemostatic plug/clot inside a blood vessel or heart chamber

Question 4

What is an emboli?

Answer 4

A portion of the thrombus that breaks away and may get stuck in capillaries

Question 5

What does an arterial clot look like?

Answer 5

Platelet rich (more white) bc platelets are attracted to specific injury site

Question 6

What does a venous clot look like?

Answer 6

Red blood cell rich

Question 7

What stimulates thrombus formation?

Answer 7

Atherosclerosis damages the arteriole endothelial layer, which stimulates thrombus formation

Question 8

What are 2 possible causes of arteriole physical damage?

Answer 8

1) balloon angioplasty

2) stenting

Question 9

Why are anti platelet drugs less effective in veins?

Answer 9

Bc venous thrombosis involves RBCs (not so much platelets)

Question 10

What is venous thrombosis due to?

Answer 10

Stagnant flow in veins and/or atria

Question 11

Name 3 platelet inhibitors:

Answer 11

1) Aspirin
2) Clopidogrel
3) Abiciximab

Question 12

Aspirin MOA:

Answer 12

1) Blocks COX irreversibly
2) Vascular endothelial cells have nucleus and can produce more COX –> PG12
3) Platelets do not have a nucleus and cannot produce more COX
* Balance is shifted towards PG12*

Question 13

What are 2 functions of COX?

Answer 13

1) Platelets: produces thromboxane A2, which promotes aggregation
2) Vascular endothelium: produces PGI2, which makes platelets less likely to aggregate (stabilization)
* Balance bw TXA2 and PGI2 determines how sticky platelets will be*

Question 14

Clopidogrel = prodrug that is converted into active form by CYP2C19

Answer 14

CYP2C19 genetic variation decreases effect

Question 15

Clopidogrel MOA:

Answer 15

1) Prevents ADP from binding to platelets (irreversible)
2) GPIIb/GPIIIa receptor activation inhibited
3) Fibrinogen cannot link platelets –> aggregation is decreased

Question 16

Clopidogrel AEs:

Answer 16

1) Neutropenia
2) Thrombotic thrombocytopenia purpura
3) Hemorrhage: GI, cerebral
4) Rash
5) Respiratory: URI, rhinitis, SOB, cough

Question 17

Clopidogrel indication:

Answer 17

1) Prevention of ischemic stroke and MI

2) Routine use during stent insertion during MI

Question 18

Clopidogrel prolongs bleeding for ___ days

Answer 18

7-10

Question 19

Abciximab MOA:

Answer 19

Monoclonal antibody against GPIIb/IIIa receptor that prevents fibrinogen from binding and linking platelets (platelet aggregation cannot occur)

Question 20

Abciximab administration:

Answer 20

IV

Question 21

Look at medchem notes

Answer 21

for heparin

Question 22

Heparin indication:

Answer 22

1) Arterial and venous thrombosis prevention (eg: post-op hip replacement, thrombolytic tx)
2) Pulmonary embolism and acute MI tx

Question 23

What are the anti-coagulation DOCs in pregnancy?

Answer 23

1) heparin
2) LMWH
bc does not cross placenta

Question 24

What is the antidote for heparin induced hemorrhage?

Answer 24

Protamine sulfate (give IV)

Question 25

Protamine sulfate AE:

Answer 25

Anaphylaxis in pts previously treated with protamine

Question 26

Heparin and LMWH adminsitration:

Answer 26

- IV - SC (LMWH not as deep) * LMWH has more predictable effects*

Question 27

Warfarin MOA:

Answer 27

Vitamin K antagonist

Question 28

Why is warfarin losing popularity?

Answer 28

Bc needs constant monitoring for INT

Question 29

Warfarin adminsitration:

Answer 29

PO

Question 30

Warfarin anticoagulation effects is seen after ___:

Answer 30

8-12 hours (management: if immediate effect is needed, heparin is also administered)

Question 31

What is the antidote for warfarin induced hemorrhage/warfarin OD?

Answer 31

Vitamin K

Question 32

Name a LMWH:

Answer 32

Enoxaparin

Question 33

Enoxaparin MOA:

Answer 33

1) Increases effects of anti-thrombin III (has higher specificity for Factor X vs Factor II) * not orally active*

Question 34

Enoxaparin indication:

Answer 34

1) Prevention of post-op DVT/PE 2) Unstable angina 3) Ischemic stroke 4) Maintenance of extracorporeal circulation during surgery/dialysis

Question 35

Name 2 AEs of warfarin:

Answer 35

1) Bleeding disorders | 2) MANY DIs (including dietary Vitamin K)

Question 36

Can warfarin be taken during pregnancy?

Answer 36

No - teratogenic and may cause abortion

Question 37

What is pro-thrombin time?

Answer 37

Measurement (in seconds) of extrinsic pathway

Question 38

What is the target INR?

Answer 38

2-3 | INR ≤2 may lead to thrombotic complications, INR ≥ 3 may lead to bleeding

Question 39

Name 2 novel oral anticoagulants (NOACs):

Answer 39

1) Dabigatran: direct, irreversible thrombin imhibitor | 2) Rivaroxaban: direct factor Xa inhibitor

Question 40

Why are NOACs gaining popularity?

Answer 40

Bc they are - Orally active - More predictable than warfarin - Have greater TI than warfarin and heparin

Question 41

NOACs indication:

Answer 41

1) Percutaneous cardiac interventions 2) VT prevention and management 3) Post-op hip/knee replacement

Question 42

What enhances bleeding effect of dabigatran?

Answer 42

- NSAID (also seen in rivaroxaban) | - SSRI/SNRI

Question 43

What is the antidote for dabigatran induced haemorrhage and how does it work?

Answer 43

Idarucizumab - monoclonal antibody that binds dabigatran with greater affinity than

Question 44

Rivaroxaban indication:

Answer 44

1) VT prevention in adults undergoing hip/knee replacement surgery 2) Stroke and embolism prevention in adults w/ non-valvular atrial fibrillation 3) Recurrent DVT/PE prevention following acute DVT in adults

Question 45

What is the antidote for rivaroxaban induced haemorrhage and how does it work?

Answer 45

Andexanet alfa IV - modified Factor Xa that binds direct factor Xa inhibitor

Question 46

What is the physiological action of plasminogen/plasmin?

Answer 46

Plasminogen bound to fibrin is converted to plasmin via tissue plasminogen activator (tPA) --> plasmin breaks down fibrin --> clot is dissolved and is handled by body

Question 47

tPA indication:

Answer 47

1) mi 2) massive PE 3) acute ischemic stroke

Question 48

When is tPA tx most beneficial?

Answer 48

When given 4.5 hours after sx onset

Question 49

What is one drawback of fribinolytic drugs?

Answer 49

They cannot distinguish bw fibrin of a good hemostatic plug and fibrin of unwanted thrombosis (therefore may cause bleeding in unknown lesion - peptic ulcers)

Question 50

Name 2 fibrinolytic inhibitors:

Answer 50

1) Tranexamic acid | 2) Aminocaproic acid

Question 51

Fibrinoytic inhibitors MOA:

Answer 51

1) Lysine analogues that bind to and inhibit plasminogen and plasmin 2) Clot is stabilized

Question 52

Fibrinolytic inhibitors indication:

Answer 52

1) Reduction of peri- and post- op bleeding esp in pts with bleeding disorders