Haemostasis - Anti-Coagulant Therapy

Question 1

indications for anticoagulation

Answer 1

venous thrombosis
atrial fibrillation
mechanical prosthetic heart valve

Question 2

what is heparin? what cells produce it?

Answer 2

GAG, produced by mast cells, anticoagulant

Question 3

actions of unfractionated heparin

Answer 3

enhancement of antithrombin [Inactivation of thrombin (Hep binds AT + Thrombin)
Inactivation of FXa (Hep binds AT only)
(Inactivation of FIXa, FXIa, FXIIa)]

Question 4

actions of low molecular weight heparin

Answer 4

Contain pentasaccharide sequence for binding AT

Predictable dose response in most cases so does not require monitoring (cf UFH)

Question 5

how is unfractionated heparin administered?

Answer 5

intravenous

Question 6

how is low molecular weight heparin administered?

Answer 6

subcutaenous

Question 7

describe a graph showing the relationship between dose of UFH and LMWH to APPT

Answer 7

both curves

UFH steeper curve

Question 8

what are coumarins?

Answer 8

vitamin K antagonists

Question 9

list an example of a coumarin

Answer 9

warfarin

Question 10

mechanism of action of warfarin

Answer 10

inhibits vitamin K epoxide reductase > reduces production of functional coagulation factors

Question 11

does warfarin administration require monitoring?

Answer 11

yes, due to narrow therapeutic index

many dietary, physiological and drug interactions

Question 12

is the action of warfarin reversible?

Answer 12

yes

Question 13

how to reverse warfarin action slowly?

Answer 13

vitamin K administration

Question 14

how to reverse warfarin action rapidly?

Answer 14

by infusion of coagulation factors:
Prothrombin Complex Concentrate- contains Factors II, VII, IX and X or
Fresh Frozen Plasma

Question 15

side effects of warfarin

Answer 15

bleeding
skin necrosis
purple toe syndrome
embryopathy - chondrodysplasia punctata

Question 16

skin necrosis when taking warfarin

Answer 16

Severe Protein C deficiency
2-3 days after starting Warfarin
Thrombosis predominantly in adipose tissues

Question 17

purple toe syndrome when taking warfarin

Answer 17

Disrupted atheromatous plaques bleed

Cholesterol emboli lodge in extremities

Question 18

chondrodysplasia punctata when taking warfarin

Answer 18

Early fusion of epiphyses

Warfarin teratogenic in 1st trimester

Question 19

what is INR?

Answer 19

international normalised ratio

used to monitor patients on warfarin

Question 20

how to calculate INR?

Answer 20

patient prothrombin time to normal prothrombin time

Question 21

target INR is usually?

Answer 21

2-3

Question 22

describe the relationship between bleeding risk and INR on a graph

Answer 22

steep curve

as INR increases, so does bleeding risk

Question 23

resistance to warfarin

Answer 23

lack of patient complicance
diet, increased vitamin K intake
increased metabolism Cyt P450 (CYP2C9)
reduced binding (VKORC1)

Question 24

which DOACs act to inhibit factor Xa?

Answer 24

rivaroxaban
apixaban
edoxaban

Question 25

which DOACs act to inhibit factor IIa?

Answer 25

dabigatran

Question 26

comparison between warfarin and DOACs

Answer 26

W: slow onset, variable dosing, many interactions and food effect, requires monitoring, reversible with vit K, PCC DOACs: rapid onset, fixed dosing, no food effect, few interactions, no monitoring, some renal dependence, antidote for dabigatran

Question 27

choice of anticoagulant for initial treatment of venous thrombosis

Answer 27

DOAC or LMWH for first few days followed by DOAC or warfarin

Question 28

choice of anticoagulant for long term treatment of venous thrombosis

Answer 28

DOAC or warfarin

Question 29

choice of anticoagulant for treatment atrial fibrillation

Answer 29

DOAC or warfarin

Question 30

choice of anticoagulant for mechanical prosthetic heart valve

Answer 30

Warfarin (DOACs not effective and should be avoided)

Question 31

choice of anticoagulant for prophylactic treatment following surgery

Answer 31

LMWH or DOAC

Question 32

choice of anticoagulant for prophylactic treatment during pregnancy

Answer 32

LMWH (DOACs not safe in pregnancy)