Anticoagulants Flashcards
(25 cards)
2 main types of Heparin
-Unfractionated ‘standard’
-Low Molecular Weight
What are anticoagulant drugs?
-Anticoagulant drugs interfere with secondary haemostasis (i.e.
coagulation factors).
-We tend to distinguish them from antiplatelet drugs or thrombolytic therapies.
What are the different kinds of anticoagulants?
-Oral: Warfarin/ DOACs
-Parental: Heparin (UFH), LMWH, Penta saccharides
Antiplatelets vs anticoagulants
-Antiplatelet medications are of greater efficacy in arterial thromboses than venous thromboembolism (platelets play a greater role in thrombosis due to ‘shear stress’ in arterial flow).
=Used in acute coronary syndromes and ischaemic
cerebrovascular diseases.
-Anticoagulants can be used for both arterial and venous thromboses.
What are Heparins?
-Heparins are glycosaminoglycans which act as anticoagulants.
- Heparin can be given parenterally as unfractionated heparin (UFH, bolus and continuous IV infusion/ subcutaneous) or low molecular weight heparin (LMWH- subcutaneously once daily).
Heparins mechanism of action
-Potentiates action of antithrombin (AT): a naturally circulating anticoagulant which itself inhibits Factor Xa and thrombin
=Binding of pentsaccharide sequence (AT and Xa) induces conformational change
-UFH: enhanced AT effect on FXa and thrombin
-LMWH: Greater effect on FXa but less on thrombin
Heparins mechanism of action
-Potentiates action of antithrombin (AT): a naturally circulating anticoagulant which itself inhibits Factor Xa and thrombin
=Binding of pentsaccharide sequence induces conformational change
Main use of LMWH
-PE
-DVT
-Acute Coronary Syndrome
-Thromboprophylaxis (not in renal failure)
Monitoring and reversal of UFH
-Infusions monitored and adjusted using APTT every 4-6 hrs (daily once stable)
-Half-life short (100 minutes) so high APTT managed by stopping heparin
=Good for where rapid reversibility required (high bleeding risk, severe renal failure)
-Protamine (sulphate) reverses effect
Monitoring and reversal of LMWH
-Due to predictable bioavailability, monitoring rarely required
-Anti-Xa assay used instead of unreliable APTT here
-Reversal with protamine but only achieves 60%
-Half-life 4 hours
Complications of Heparins
-Bleeding
-Heparin Induced Thrombocytopenia
-Osteoporosis in prolonged use
=Rarer in LMWH
Describe Heparin Induced Thrombocytopenia (HIT)
-Immune mediated reaction
-Develops at 5-10 days of treatment
-Prothrombotic condition
-Use a non-heparin anticoagulant
Mechanism of Warfarin
-Vitamin K antagonist
=Prevents Vitamin K recycling
=Reduced rate of synthesis of factors
=Takes 5 days as pre-existing factors remain (pro-thrombotic first few days as depletes natural anticoagulants faster than factors= can cause skin and soft tissue necrosis so cover with LMWH/ slow initiation)
-Reduces factors 2,7,9,10 (and natural anticoagulants Protein C and Protein S)
-Acts on extrinsic pathway
Main uses of Warfarin
-DVT
-PE
-AF
-Artificial heart valves
-Rheumatic HD
-Cardioversion
Monitoring of warfarin
-INR (international normalised ratio)- universal standard for corrected PT time (ratio of PT time to population average)
-Normal= 1
-Target 2-3 sometimes higher in indication and individuals
=Regular blood tests to adjust level
Dosing of Warfarin
-Warfarin metabolised by CYP450 system
=many drugs, intercurrent illness and diet/alcohol can interfere
=Increase INR (enzyme inhibitor), low INR (enzyme inducers= anti-epileptics)
-Omeprazole, erythromycin, cranberry juice increase effect of warfarin
=Appropriate counselling
High INR problems
-Haemorrhage (brain and bowel)
-Teratogenic (early pregnancy)
-Soft tissue necrosis
High INR problems
-Haemorrhage
-Teratogenic
-Soft tissue necrosis
Management for minor bleeding on warfarin/ INR>8
- Stop warfarin
- Oral or IV vitamin K (1-2mg)
- Re-introduce at a lower dose when bleeding resolves
Management for serious bleeding on warfarin/ INR>1.1
- Stop warfarin
- IV vitamin K (5-10mg)
- Prothrombin complex concentrate (Beriplex)
Groups of DOACs
-Direct thrombin inhibitors
=Dabigatran
-Factor Xa inhibitors
=Apixaban
=Rivaroxaban
=Edoxaban
Main uses of DOAC
-VTE prophylaxis after knee and hip replacement and treatment
-AF (non-valvular)
-Acute coronary syndrome
Disadvantages of DOAC
-Unsafe in advanced renal impairment
-Not as effective as warfarin for metallic heart valves
-Bleeding
-Reversal agents pending
Disadvantages of DOAC
-Unsafe in advanced renal impairment
-Not as effective as warfarin for metallic heart valves
-Bleeding
-Reversal agents pending (Idarucizumab for dabigatran)
