The haematological system and skin - pharmacology Flashcards
Warfarin - MOA
Competitively inhibits vitamin K epoxide, which is necessary for production of clotting factors II, VII, IX, X
Warfarin - route
Oral
Warfarin - factors inhibited
II, VII, IX, X
Warfarin monitoring
- INR
- Yellow book: documents patients target INR, last INR, their current does of warfarin and when their next INR
Which laboratory coagulation test is derived from INR
Prothrombin time
INR - standard target
2.5 (range 2-3)
INR - target in mechanical heart valves
2.5 - 3.5
Factors affecting INR
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
Management of warfarin - major bleeding
Stop warfarin
Administer IV vitamin K
Administer prothrombin complex ( or fresh frozen plasma if prothrombin complex unavailable)
Management of warfarin - minor bleeding
Stop anticoagulants
Administer IV vitamin K
Repeat INR after 24 hours, may need further vitamin K
Management of warfarin - no bleeding with INR > 8
Stop anticoagulants
Administer IV or oral vitamin K
Repeat INR after 24 hours
Management of warfarin - no bleeding with INR between 5-8
Withhold 1-2 doses of warfarin and restart at reduced dose
Review maintenance dose of warfarin
Heparin - route
Subcutaneous or IV
Heparin - MOA
Activates antithrombin increasing its anticoagulant effect (by inactivating prothrombin, XIa, IXa, Xa and impairing platelet function)
Heparin - clinical uses
When rapid onset/offset of action needed e.g., initial treatment of VTE, anticoagulant ‘bridging therapy’ to cover surgery in high thrombotic risk patients
Which laboratory coagulation test does heparin effect and what effect is this?
Prolongs APTT
Unfractionated heparin - Side effects
Heparin induced thrombocytopenia
Unfractionated heparin - Side effects
Heparin induced thrombocytopenia
Unfractionated heparin - reversal agent
Protamine
Unfractionated heparin - monitoring
APTT ratio (target 2.0) every 6 hours until stable
Unfractionated heparin - target APTT
2.0
LMWH - MOA
Majority of effect isa anti Xa (indirectly through antithrombin). Lesser degree of thrombin inhibition
LMWH - monitoring
Not needed unless severe renal failure or extremes of body weight
Heparin-induced thrombocytopenia - definition and management
Definition
- Drop of platelets by more than 30%
Management
- Stop heparin
- Consider alternative anticoagulation
Can APTT be used to assess LMWH effect?
No - only unfractionated heparin
Management of heparin overanticoagulation/bleeding
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
Fondaparinux - definition
Anticoagulant that is chemically related to LMWH
Difference between fondaparinux and LMWH
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
Fondaparinux - route
Subcutaneous injection
Fondaparinux - MOA
Inhibits factor Xa
Fondaparinux - reversal agent
None
DOACs - MOA
Factor Xa inhibitors
Management of DOAC over anticoagulation/bleeding
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
DOACs - monitoring
Not required
Anticoagualation - options for rapid onset
Heparin
- usually LMWH s/c
- Start warfarin PO at same time
- Stop heparin once iNR in therapeutic range for 2 consecutive days
DOAC
Anticoagulation - options for slow induction
Warfarin
DOAC
