Anticoagulant Drugs Flashcards
What are some indications for anticoagulant drugs?
Venous thrombosis
AF
What do anticoagulant drugs target?
The formation of the fibrin clot
Describe heparin
Potentiates antithrombin
Immediate effect
Parenteral (IV or SC)
2 forms- unfractionated, low molecular weight (LMWH)
Where do unfractionated and LMWH act?
Antithrombin III inhibition of Thrombin (more so unfractionated)
AT III inhibition of V/Xa (more so LMWH)
How is unfractionated heparin monitored?
aPTT
How is LMWH monitored?
Anti-Xa assay, but usually no monitoring required as predictable response
What are some complications of heparin?
Bleeding
Heparin induced thrombocytopenia (with thrombosis) HITT - monitor FBC in patients on heparin
Osteoporosis with long term use
How should heparin be reversed?
Stop heparin (short t1/2) Occasionally in severe bleeding- Protamine sulphate Reverses antithrombin effect Complete reversal for unfractionated Partial reversal for LMWH
What are the coumarin anticoagulants?
Warfarin
Phenindione
Acenocoumarin
Phenprocoumon
What is the mechanism of action of the coumarin anticoagulants?
Inhibition of Vit K
Describe the Vit K Dependent factors
Factors II (prothrombin), VII, IX & X- Protein C and protein S Synthesised in liver Require vitamin K for final carboxylation step essential for function
What is the action of Vit K?
Carboxylation of glutamic acid residues in factors
II, VII, IX and X (as well as Protein C and S)
What is the mechanism of action of warfarin?
Blocks the ability of Vitamin K to carboxylate the Vitamin K dependent clotting factors, thereby reducing their coagulant activity
Describe warfarin therapy
Initiation- rapid for acute thrombosis in hospital with heparin, slow for AF in community and for liver failure, malnourished, elderly etc
Narrow therapeutic window- therapy needs monitored
Stabilisation
Maintenance- dose same time every day (6pm recommended)
What is the INR equation?
(Patients PT in secs/Mean Normal PT in secs) ^ISI (International Sensitivity Index)
What is the INR?
A mathematical “correction” (of the PT ratio) for differences in the sensitivity of thromboplastin reagents
Allows for comparison of results between labs and standardizes reporting of the prothrombin time
What factors may influence bleeding risk in warfarin?
Intensity of anticoagulation Concomitant clinical disorders Concomitant use of other medications Beware drug interactions Quality of management
What are some bleeding complications?
Mild- skin bruising, epistaxis, haematuria
Severe- GI, intracerebral, significant drop in Hb
How is warfarin reversed?
No action Omit Warfarin dose(s) Administer oral Vitamin K Administer clotting factors (FFP or factor concentrates) Clinical and laboratory assessment of response
How is bleeding managed?
Dependant on- Severity of bleeding, INR
Speed of action -
Vitamin K - 6 hours
Clotting factors - immediate
What are some new anticoagulants?
Oral direct thrombin inhibitors- dabigatran
Oral Xa inhibitors- rivaroxaban, apixaban
No monitoring required, less drug interactions, no specific antidote for reversal currently
What does warfarin have an effect on?
Prothrombin, VIIa, IXa and Xa
When should new anticoagulants be used?
Used instead of LMWH as prophylaxis in elective hip and knee replacement surgery
Used for selected patients for stroke prevention in atrial fibrillation
Used for treatment of DVT/PE
