Week 2 part 3 Flashcards
Indications for anticoagulant drugs
Venous thrombosis
Atrial fibrillation
Heparin
Potentiates antithrombin
Immediate effect
Parenteral (iv or sc)
2 forms - unfractionated & LMWH
Heparin mechanism of action
inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.
Monitoring of heparin
Activated partial thromboplastin time (APTT) for unfractionated
Anti-Xa assay for LMWH but usually no monitoring of LMWH is required as more predictable response
Heparin complications
Bleeding
Heparin induced thrombocytopenia (with thrombosis) HITT - monitor FBC in patients on heparin
Osteoporosis with long term use
Heparin - reversal
Stop the heparin (short half-life)
Occasionally in severe bleeding -
Protamine sulphate - Reverses antithrombin effect: Complete reversal for unfractionated, Partial reversal for LMWH
Coumarin anticoagulants examples
warfarin
phenindione
acenocoumarin
phenprocoumon
Coumarin anticoagulants mechanism of action
inhibition of vitamin K
Vitamin K
Fat soluble vitamin
Absorbed upper intestine
Requires bile salts for absorption
Final carboxylation of clotting factors II, VII, IX and X
Action of Vitamin K
Carboxylation of glutamic acid residues in factors II, VII, IX and X (as well as Protein C and S).
Warfarin mechanism of action
Inhibits epoxide reductase preventing the reduction of vitamin K to its active hydroquinone form
This in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X and protein C.
What does INR stand for?
International Normalized Ratio
INR Equation
INR = Patients PT in seconds / Mean normal PT in seconds
PT = Pro-thrombin time
Warfarin: Major Adverse Effects
Haemorrhage
BEWARE DRUG INTERACTIONS
What factors may increase warfarin bleeding (adverse effect)?
Intensity of anticoagulation Concomitant clinical disorders Concomitant use of other medications BEWARE DRUG INTERACTIONS Quality of management
Bleeding complications of warfarin
Mild = skin bruising, epistaxis, haematuria Severe = gastro-intestinal, intracerebral, significant drop in Hb
Reversal of warfarin
No action
Omit Warfarin dose(s)
Administer oral Vitamin K
Administer clotting factors (factor concentrates)
Speed of action of Vitamin K and clotting factors in warfarin reversal
Vitamin K - 6 hours
Clotting factors - immediate
Thrombin inhibitors examples
epirudin, desirudin, bivalirudin and argatroban, dabigatran
Dabigatran adverse effects (direct thrombin inhibitor)
Unsurprisingly haemorrhage is the major adverse effect.
Doses should be reduced in chronic kidney disease and dabigatran should not be prescribed if the creatinine clearance is < 30 ml/min.
Xa inhibitors examples
Edoxaban, Rivaroxaban, Apixaban
Remember Xa converts prothrombin to thrombin
Reversal of dabigatran
Idarucizumab cab be used for rapid reversal of the anticoagulant effects of dabigatran.
Reversal of Edoxaban, Rivaroxaban, Apixaban (direct factor Xa inhibitors)
Andexanet alfa
Aspirin mechanism of action
Anti-platelet drug
Inhibits cyclo-oxygenase which is necessary to produce Thromboxane A2 (a platelet agonist released from granules on activation).
