15) Anticoagulant Therapy

Question 1

What are the constituents of Virchow’s triad?

Answer 1

Hypercoagulability
Endothelial damage
Stasis

Question 2

What factors/conditions can affect hypercoagulability?

Answer 2

Smoking
OCP
Heart valves
Malignancy
Protein C and S deficiency
SLE

Question 3

What factors/conditions can cause endothelial damage?

Answer 3

Atheroma
HTN
Toxins (cigarettes)

Question 4

What factors/conditions cause stasis?

Answer 4

Venous - immobility

Arterial - cardiac abnormality (AF)

Question 5

What is the mechanism of action of warfarin?

Answer 5

Inhibits production of vitamin K dependent clotting factors

Question 6

What are the vitamin K depending clotting factors?

Answer 6

Prothrombin (II), VII, IX, X

Question 7

Describe the onset and offset time of warfarin:

Answer 7

Slow onset
Slow offset (need to stop 3 days before surgery)

Question 8

Describe the pharmacokinetics of warfarin (ADME):

Answer 8

Good GI absorption
Heavily protein bound
Metabolised in liver by cytochrome P450

Question 9

What are some adverse effects of warfarin?

Answer 9

Teratogen (trimester 1) and can cause brain haemorrhage (T3)

Excessive bleeding - intracranial, epistaxis, GI

Question 10

How can warfarin be monitored?

Answer 10

Prothrombin time

INR

Question 11

What is the prothrombin time?

Answer 11

Citrated plasma clotting time

Question 12

What is the INR?

Answer 12

Standard value of PT between labs

Question 13

What drugs can inhibit the hepatic metabolism of warfarin?

Answer 13

Amiodarone, quinolone, metronidazole, alcohol

Question 14

What drugs increase warfarin’s effect?

Answer 14

Aspirin
Cephalosporins (reduce vit K from gut bacteria)
NSAIDs

Question 15

What drugs are inhibitors of warfarin?

Answer 15

Anti-epileptics
Rifampicin
St John’s Wort

Question 16

When is warfarin used?

Answer 16

DVT, PE, AF, prosthetic valves

Question 17

How can the action of warfarin be reversed?

Answer 17

Stop warfarin and give: IV vit K, fresh frozen plasma or prothrombin complex concentrate

Question 18

Describe the structure of heparin:

Answer 18

Glycosaminoglycan with a glucose backbone

Question 19

What is the mechanism of action of unfractionated heparin?

Answer 19

Activate anti-thrombin III that de-activates factors Xa, IIa, IXa

Question 20

What clotting factor is affected by low molecular weight heparin?

Answer 20

Xa

Question 21

How do unfractionated and LMWH heparin vary in structures?

Answer 21

Unfractionated: variable length heparin chains (20kDa)
LMWH: small chains (4kDa)

Question 22

How do unfractionated and LMWH heparin vary in route of administration?

Answer 22

Unfractionated: IV
LMWH: SC

Question 23

Why is unfractionated heparin able to inhibit thrombin, when LMWH can’t?

Answer 23

To catalyse inhibition of thrombin by ATIII, heparin has to bind to molecules simultaneously and only unfractionated is large enough to do this

Question 24

Describe the onset and offset time of heparin:

Answer 24

Rapid onset and offset of action

Question 25

Describe the pharmacokinetics of LMWH (ADME):

Answer 25

Poor GI absorption High bioavaliability Long half life

Question 26

How can unfractionated heparin be monitored?

Answer 26

Activated partial thromboplastin time

Question 27

When is heparin used?

Answer 27

Prevention of thromboembolsim (post op, immobility) DVT/PE and AF Acute coronary syndromes Pregnancy

Question 28

What are some of the adverse effects of heparin?

Answer 28

Bruising/bleeding Heparin induced thrombocytopenia Osteoporosis

Question 29

Explain heparin-induced thrombocytopenia:

Answer 29

Heparin and PF4 on platelets are immunogenic, IgG complexes form activating more platelets until platelets are depleted and get thromboses in area

Question 30

How should heparin induced thrombocytopenia be managed?

Answer 30

Stop heparin and add hirudin

Question 31

How can heparin be reversed?

Answer 31

Stop heparin and if actively bleeding give protamine sulphate

Question 32

Name some antiplatelet drugs:

Answer 32

Aspirin Clopidogrel Dipyridamole Glycoprotein IIb/IIIa inhibitors

Question 33

What is the mechanism of action of aspirin?

Answer 33

Inhibition of thromboxane A2 production by COX enzymes

Question 34

What is the mechanism of action of clopidogrel?

Answer 34

Inhibits P2Y12 ADP receptor involved in platelet activation

Question 35

When is clopidogrel given?

Answer 35

ACS and PCI

Question 36

What is the mechanism of action of dipyridamole?

Answer 36

Phosphodiesterase inhibitor - positive ionotrope and vasodilator

Question 37

When is dipyridamole given?

Answer 37

Secondary prevention of stroke

Question 38

How do glycoproteins IIb/a receptor antagonists work?

Answer 38

Block fibrinogen from binding to these receptors which causes platelet aggregation

Question 39

When are glycoprotein IIa/b receptor antagonists used?

Answer 39

High risk ACS, post PCI