The haematological system and skin - pharmacology

Question 1

Warfarin - MOA

Answer 1

Competitively inhibits vitamin K epoxide, which is necessary for production of clotting factors II, VII, IX, X

Question 2

Warfarin - route

Answer 2

Oral

Question 3

Warfarin - factors inhibited

Answer 3

II, VII, IX, X

Question 4

Warfarin monitoring

Answer 4

• INR
• Yellow book: documents patients target INR, last INR, their current does of warfarin and when their next INR

Question 5

Which laboratory coagulation test is derived from INR

Answer 5

Prothrombin time

Question 6

INR - standard target

Answer 6

2.5 (range 2-3)

Question 7

INR - target in mechanical heart valves

Answer 7

2.5 - 3.5

Question 8

Factors affecting INR

Answer 8

Individual variation/genetic

Drugs (including alcohol) can potentiate the effects of warfarin

Diet e.g., Vitamin K content

Intercurrent illness

Mistake e.g., elderly, visually impaired

Question 9

Management of warfarin - major bleeding

Answer 9

Stop warfarin

Administer IV vitamin K

Administer prothrombin complex ( or fresh frozen plasma if prothrombin complex unavailable)

Question 10

Management of warfarin - minor bleeding

Answer 10

Stop anticoagulants

Administer IV vitamin K

Repeat INR after 24 hours, may need further vitamin K

Question 11

Management of warfarin - no bleeding with INR > 8

Answer 11

Stop anticoagulants

Administer IV or oral vitamin K

Repeat INR after 24 hours

Question 12

Management of warfarin - no bleeding with INR between 5-8

Answer 12

Withhold 1-2 doses of warfarin and restart at reduced dose

Review maintenance dose of warfarin

Question 13

Heparin - route

Answer 13

Subcutaneous or IV

Question 14

Heparin - MOA

Answer 14

Activates antithrombin increasing its anticoagulant effect (by inactivating prothrombin, XIa, IXa, Xa and impairing platelet function)

Question 15

Heparin - clinical uses

Answer 15

When rapid onset/offset of action needed e.g., initial treatment of VTE, anticoagulant ‘bridging therapy’ to cover surgery in high thrombotic risk patients

Question 16

Which laboratory coagulation test does heparin effect and what effect is this?

Answer 16

Prolongs APTT

Question 17

Unfractionated heparin - Side effects

Answer 17

Heparin induced thrombocytopenia

Question 18

Unfractionated heparin - Side effects

Answer 18

Heparin induced thrombocytopenia

Question 19

Unfractionated heparin - reversal agent

Answer 19

Protamine

Question 20

Unfractionated heparin - monitoring

Answer 20

APTT ratio (target 2.0) every 6 hours until stable

Question 21

Unfractionated heparin - target APTT

Answer 21

2.0

Question 22

LMWH - MOA

Answer 22

Majority of effect isa anti Xa (indirectly through antithrombin). Lesser degree of thrombin inhibition

Question 23

LMWH - monitoring

Answer 23

Not needed unless severe renal failure or extremes of body weight

Question 24

Heparin-induced thrombocytopenia - definition and management

Answer 24

Definition
- Drop of platelets by more than 30%

Management
- Stop heparin
- Consider alternative anticoagulation

Question 25

Can APTT be used to assess LMWH effect?

Answer 25

No - only unfractionated heparin

Question 26

Management of heparin overanticoagulation/bleeding

Answer 26

Stop heparin - short half-life, may be sufficient Local measures e.g., apply pressure Consider tranexamic acid If bleeding, consider protamine sulphate Look for cause e.g., incorrect dose, new renal failure Before restarting check risk: benefit ratio

Question 27

Fondaparinux - definition

Answer 27

Anticoagulant that is chemically related to LMWH

Question 28

Difference between fondaparinux and LMWH

Answer 28

Fondaparinux is synthetic, LMWH is porcine-derived Only has inhibits factor Xa, whereas LMWH also inhibits thrombin Fondaparinux prolongs APTT, whereas LMWH cannot be used to assess APTT

Question 29

Fondaparinux - route

Answer 29

Subcutaneous injection

Question 30

Fondaparinux - MOA

Answer 30

Inhibits factor Xa

Question 31

Fondaparinux - reversal agent

Answer 31

None

Question 32

DOACs - MOA

Answer 32

Factor Xa inhibitors

Question 33

Management of DOAC over anticoagulation/bleeding

Answer 33

Stop DOAC – short half-life, may be sufficient Local measures e.g., apply pressure Consider tranexamic acid Idarucizumab is now available for the reversal of dabigatran Antidote to Xa inhibitors not yet available. In the meantime, in life threatening bleeding consider prothrombin complex concentrate Look for cause e.g., incorrect dose, new renal failure Before restarting check risk: benefit ratio

Question 34

DOACs - monitoring

Answer 34

Not required

Question 35

Anticoagualation - options for rapid onset

Answer 35

Heparin - usually LMWH s/c - Start warfarin PO at same time - Stop heparin once iNR in therapeutic range for 2 consecutive days DOAC

Question 36

Anticoagulation - options for slow induction

Answer 36

Warfarin DOAC