3.5 Anticoagulant drugs

Question 1

what are the indications for anticoagulant drugs?

Answer 1

venous thrombosis

atrial fibrillation

Question 2

How does heparin work?

Answer 2

heparin potentiates anti-thrombin III 
antithrombin III inhibits clotting factors 
-TF/VIIa
-VIII/IXa 
-V/Xa 
-thrombin 

it works by stabilizing the bond between ATIII and thrombin or factor Xa (LMWH) because of its negative charge. (AT III and clotting proteins are + charged)

Question 3

why is it important that heparin inhibits thrombin in the coagulation cascade?

Answer 3

1. thrombin cleaves fibrinogen to fibrin- final product

2. thrombin activates factors VIII/IXa which amplifies haemostasis (intrinsic pathway)

Question 4

How does protein C and protein S work?

Answer 4

protein C and S are natural anticoagulants on platelets.
they are activated by thrombin bound to thrombomodulin on endothelial cells
protcein C and S inhibit V/Xa and VIII/IX clotting factors

Question 5

How quickly does heparin work?

Answer 5

Heparin works immediately
potentiates antithrombin
IV or SC
unfractionated or LMWH

Question 6

what are the targets of LMWH?

Answer 6

thrombin or factor Xa - to help it bind to antithrombin III

Question 7

what is measured to monitor heparin?

Answer 7

activated partial thromboplastin time - APTT

for unfractionated heparin only

Question 8

what is measured to monitor LMWH?

Answer 8

usually no monitoring

anti-Xa assay can be done

Question 9

What is measured to monitor warfarin?

Answer 9

PT or INR

Question 10

what clotting factors are measured by PT?

intrinsic or extrinsic pathway?

Answer 10

TF/VIIa

extrinsic pathway

Question 11

what clotting factors are measured by aPTT?

Answer 11

VIII/Xa

intrinsic pathway for amplification

Question 12

what are the complications of heparin use?

Answer 12

bleeding
heparin induced thrombocytopaenia- HITT, monitor FBC in patients on heparin. mx: stop heparin, change drgs 
osteoporosis with long term use
allergy
rash

Question 13

How do you reverse heparin?

Answer 13

stop heparin- half life in unfractioned is 30 min, LMWH is 12 hours

protamine sulphate- doesn’t reverse anti-Xa effect

• complete reversal for heparin
• incomplete reversal for LMWH

Question 14

what is the half life of unfractioned heparin?

Answer 14

30 min

Question 15

half life of LMWH?

Answer 15

12 hours

Question 16

what are the coumarin anticoagulants?

Answer 16

warfarin
phenindione
acenocoumarin
phenprocoumon

Question 17

mechanism of action of warfarin

Answer 17

inhibit vitamin K
vit K needed for final carboxylation of clotting factors II, VII, IX, X
(protein C and S- also need carboxylation to work, so clotting may be increased in initial use of warfarin)

Question 18

where is vit K absorbed?

Answer 18

upper intestine

requires bile salts because fat soluble vitamin

Question 19

How long should you cover a patient with heparin when they are starting warfarin?

Answer 19

5-7 days

unles very slow start is an option

Question 20

synthesis of coagulation factors is reduced in warfarin therapy
true or false?

Answer 20

false

there is a synthesis of NON-FUNCTIONAL coagulation factors from the liver in antagonism of vitamin K

Question 21

does warfarin act on intrinsic or extrinsic pathway?

Answer 21

the extrinsic pathway
because factors II, VII, IX, X are inhibited through non-functional production
and extrinsic pathway is TF/VIIa

also the final common pathway (V/Xa) is inhibited

Question 22

how do you start warfarin therapy?

Answer 22

initiation- can be rapid or slow, with heparin cover
stabilization- may need dose adjustment
maintenance- take warfarin at same time every day, check levels if dose changed within a few days

Question 23

what is the INR equation?

Answer 23

INR= patient’s PT in seconds / normal PT in seconds ) ^international sensitivity ratio
the goal is 2-3

Question 24

what are the adverse effects of warfarin?

Answer 24

HAEMORRHAGE

• consider PMH- peptic ulcer disease?
• consider MH- antibiotics?
• consider diet- cranberry or grapefruit juice? dose may need to be decreased
• consider alcohol

skin bruising, epistaxis, haematuria
gastrointestinal bleeding
intracerebral bleeding- 1/200 per year get this, and 1/2 die before getting to hospital, even with normal INR
decreased Hb

Question 25

how do you manage minotir bleeding, little bruising in warfarin therapy?

Answer 25

no action

Question 26

how do you manage an INR between 3-8 with brusing on warfarin?

Answer 26

omit warfarin dose

however it takes a few days for INR to come down

Question 27

how do you manage an INR >8 with non-life threatening bleeding?

Answer 27

administer oral vitamin K

takes 6 hours to work

Question 28

how do you manage INR >8, life threatening bleeding?

Answer 28

stop warfarin
give vitamin K
give clotting gactors- factors concentrate II, VII, IX, and X give immediate reversal

Question 29

what clotting factors does warfarin inhibit?

Answer 29

factors II, VII, IX, Xa

prothrombin

Question 30

what clotting factors does dabigatran inhibit?

Answer 30

thrombin

Question 31

what is the main concern with accumulation in dabigatran?

Answer 31

it is renally excreted, so renal impairment, eg. UTI, that decreases renal excretion leads to bleeding problems

Question 32

what factors do rivaroxiban and apixaban inhibit?

Answer 32

factor Xa

Question 33

Is there a renal concern with factor Xa inhibitors rivaroxiban and apixaban?

Answer 33

no, not renally excreted

Question 34

what are the current uses of new anticoagulants?

Answer 34

instead of LMWH prophylaxis in hip and knee replacement sx
for some patients with AF
DVT/PE treatment