ANTICOAGULANTS AND ANTIPLATELETS Flashcards
How should you manage warfarin when there is a major bleed?
Stop warfarin
Give IV vitamin K and prothrombin complex
How should you manage warfarin when INR >8.0?
Stop warfarin
Give oral vitamin K (give IV if there is evidence of bleeding) and repeat dose if INR still high after 24 hours
Restart warfarin when INR <5.0
How should you manage warfarin when INR 5.0-8.0?
If bleeding:
Stop warfarin
Give IV vitamin K
Restart warfarin when INR <5
If no bleeding:
Stop 1-2 doses of warfarin and reduce subsequent maintenance dose
Whats the moa of warfarin?
Inhibits epoxide reductase which prevents reduction of vitamin K to its active hydroquinone form which then acts as a cofactor in the carboxylation of clotting factor II, VII, IX, X and protein C.
I.e. it inhibits vitamin K dependant clotting factors
When is warfarin indicated?
Mechanical heart valves
Second line after DOACs for VTE and AF
Whats the target INR when on warfarin for mechanical heart valves?
Depends on valve type and location - mitral valves require a higher INR than aortic
Whats the target INR when on warfarin for VTE?
2.5
Whats the target INR when on warfarin for AF?
2.5
How is warfarin monitored?
Using international normalised ratio (INR) and using prothrombin time
What factors may potentiate warfarin?
Live disease
P450 enzyme inhibitors e.g. amiodarone and ciprofloxacin
Cranberry juice
Drugs which displace warfarin from plasma albumin e.g. NSAIDs
Drugs that inhibit platelet function e.g. NSAIDs
What are side efefcts of warfarin?
Haemorrhage
Teratogenic (not breast feeding)
Skin necrosis
Purple toes
Why is warfarin usually started concurrently with heparin at first?
As when you first start warfarin, biosynthesis of protein C is reduced = temporary procoagulant state
Whats the MOA of unfractionated heparin?
Forms a complex with antithrombin III and inhibits thrombin, factors IXa, Xa, XIa and XIIa
Whats the moa of LMWH?
Activates antithrombin III and forms a complex that inhibits factor Xa
What are examples of DOACs?
Dabigatran
Rivaroxaban
apixaban
Edoxaban
Whats the moa of dabigatran?
Direct thrombin inhibitor
Whats the moa of rivaroxaban, apixaban, edoxaban?
Direct factor Xa inhibitor
What is fondaparinux?
A synthetic pentasaccharide that inhibs activated factor Xa
(shaped like heparin)
How is unfractionated heparin administrated?
IV
How is LMWH administrated?
Subcutaneously
What are examples of LMWH?
Dalteparin
Enoxaparin
Nadroparin
How is fondaparinux administered?
Subcutaneous injection
What are contraindications for all heparins?
Acute bacterial endocarditis
After major trauma
Epidural anaesthesia with treatment disease
Haemophilia/other haemorrhagic disorders
Peptic ulcers
Recent cerebral haemorrhage
Recent eye Surrey, NS surgery
Spinal anaesthesia with treatment diseases
Thrombocytopenia
What are the SE for all heparins?
Haemorrhage
Heparin-induced skin reaction
Hyperkalaemia
Osteoporosis
Alopecia
Spinal haematoma
What monitoring is done for all heparins?
Platelet count - before starting treatment, and ongoing - to check for heparin-induced thrombocytopenia (if taking for >4 days)
Plasma K+ concentration before starting and regularly there after - hyperkalaemia (if taking for >7 days)
Why is LMWH used more routinely than unfractionated heparin?
LMWH doesnt require anticoagulant monitoring
Decreased risk of heparin-induced thrombocytopenia and osteoporosis
Duration of action is longer so once-daily subcutaneous administration may be possible
How does the duration of action of heparins differ?
LMWH has longer duration of action than unfractionated heparin
What monitoring should be done for heparin?
LMWH - no routine monitoring required
Unfractionated - monitor activated partial thromboplastin time
When is unfractionated heparin more useful than LMWH?
Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly. Also useful in renal failure
How do you reverse a heparin overdose?
Protamine sulphate (note it only partially reverses the effects of LMWH)
What are options for parenteral anticoagulation?
Unfractionated heparin
LMWH
Fondaparinux
Direct thrombin inhibitors
Whats an example of a direct thrombin inhibitor taken parenterally?
Bivalirudin
What are the options for oral anticoagulation?
DOACs
Warfarin
What are the examples of DOACs licensed for use in the UK?
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
Why is warfarin still needed as a drug?
It’s used for patients with metallic heart valves
What metabolises warfarin?
CYP450-2C9
What can reduce P450s anticoagulation effect?
CYP2C9 inducers - rifampicin, carbamazepine, phenytoin, pyrimidone
Some calcium supplements
ST/johns wort
What can increase the action of warfarin and therefore increase bleeding risk?
Altered intestinal flora with reduced intestinal vitamin K synthesis - antibiotics
Inhibitors of hepatic CYP2C9 - fluconazole, amiodarone, metronidazole, sulfamethoxazole, gemfibrozil
Anything that binds albumin and therefore displaces warfarin
Anything that injures GI mucosa e.g. aspirin and NSAIDs
Anything that interferes with platelet function e.g. anti-platelets
Chamomile tea
Fenugreek
Ginkgo biloba
What is INR?
International normalised ratio
It’s the prothrombin time that is agreed globally
Who should have a target INR of 3.5?
Pt with recurrent DVT or PE if already recieving anticoagulation and have an INR >2
When should warfarin be stopped regarding surgery?
5 days before but given the day before surgery if INR is >1.5
Contraindications for warfarin
Avoid use within 48 hours postpartum
Haemorrhagic stroke
Significant bleeding
Pregnancy
Allergies
?
Severe liver/kidney disease
Endocarditis in past
History of GI bleeding
Hypertension
How do we monitor warfarin?
Base-line prothrombin time
Daily INR in early days ands then at longer intervals up to every 12 weeks
What should you ensure everyone on warfarin has?
An anticoagulant treatment booklet (yellow book)
What is in an anticoagulant treatment booklet?
Records recent INR
Dosage information
Advice on anticoagulation
Alert card which should be carried by the pt at all times
Why is it suggested to take warfarin in the evening?
This is so that if you need to change the dose after a routine blood test, you can do this the same day rather than waiting until the following morning.
What foods can affect warfarin?
Foods containing lots of vitamin K e.g. green leafy veg, chickpeas, liver, egg yolks, mature /blue cheese, avocado, olive oil
Cranberry and grapefruit juice can increase effect of medication and put you at high bleeding risk
What are indications for DOACs?
Apixaban, dabigatran, edoxaban + rivaroxaban - prevention stroke, systemic embolism with non-valvular AF in specific circumstances, treating and secondary prevention or DVT/PE
Apixaban, dabigatran and rivaroxaban - prevention of VTE after elective hip/knee replacement surgery
Rivaroxaban - prevention atherothrombotic events in pt with CAD or PAD and following ACS
What monitoring is done for DOACs?
No routing anticoagulant monitoring is required
When does the anticoagulant effect of DOACs diminish after the last dose?
12-24 hours (omitted/delayed doses could lead to a reduction in anticoagulant effect BUT also means unlikely to need reversal agents)
What are reversal agents for warfarin?
Vitamin K1
Prothrombin complex concentrate
(Second line - fresh frozen plasma)
Whats the reversal agent for dabigatran?
Idarucizumab
Whats the reversal agent for apixaban or rivaroxaban?
Andexanet Alfa
