Oral anticoagulation, INR and Stroke Prevention Flashcards
Which NOAC drugs are anti factor Xa?
- Edoxaban
- Rivaroxaban
- Apixaban
Which NOAC drug is anti factor IIa?
- Dabigatran
Describe the method of action of Warfarin
- Vitamin K antagonist; reduces the biological activity (and production) of factors:
- X, IX, VII, II (1972)
- Protein C and S
- Blocks vit K epoxide reductase
- No gamma-carboxylation of glutamic acid residues so the coagulation proteins are biologically inactive (PIVKA)
Why does Warfarin not have an immediate effect?
Warfarin immediately inhibits the production of coagulation factors II, IX, VII and X and anticoagulant proteins C and S.
Existing proteins however are unaffected and continue to work until they are metabolised.
Which factors are the first to be cleared?
What is the consequence of giving a high dose of warfarin to patients with low protein C? What must be given to prevent this?
Factors VII and protein C.
The patient will initially be more susceptible to thrombus formation as the naturally occuring anticoagulant protein C is cleared before the coagulation proteins. The patient should be covered by heparin (LMWH) for at least 7 days until factor II reduces.
What factors can influence the effects of warfarin?
- Genetics
- Diet
- Adherence
What genetic components influence warfarin sensitivity?
- Cytochrome P450(2C9), which metabolizes (S)-warfarin, is considered to be most important
- CYP2C9*2 & *3 associated with lower warfarin dose and increased bleeding risk during induction
What genetic components influence warfarin resistance?
- Vitamin K epoxide reductase
- VKORC1 Asp36Tyr predicts higher dose requirement
What vitamins increase anticoagulation?
- Vitamin E
What vitamins reduce anticoagulation?
- Vitamins K, C, co-enzyme Q10
What herbs increase anticoagulation?
- Garlic
- Devil’s claw
- Dong quai
- Danshen
What herbs reduce anticoagulation?
- Korean ginseng
- Green tea
What plants reduce anticoagulation?
- St. John’s Wort
- Broccoli
- Brussel sprouts
What effects does alcohol have on anticoagulation?
Binge drinking increases anticoagulation
Regular drinking reduces anticoagulation
What medications increase anticoagulation? (as a side effect)
- Statins
- Amiodarone
- Erythromycin
- Aspirin
What medications reduce anticoagulation?
- Rifampicin
- Carbamazepine
What part of the coagulation cascade can be used to measure the effects of warfarin?
Intrinsic pathway
What does International Normalised Ratio (INR) measure?
Prothrombin time ratio:
Prothrombin time ratio = Patient’s PT(s)
GMN PT (s)
In what circumstances is warfarin cautioned?
- History of GI bleed
- Severe heart failure
- Liver disease
- Renal failure
- Alcoholism
- Mental impairment
- Thrombocytopaenia
- Coagulation disorders
- Drugs
What is the international sensitivity index?
- Use plasmas from healthy normals & OAC patients
- Compare PT for candidate reagent with International Reference (thromboplastin) Preparation (IRP)
- ISI = Slope of Orthogonal Regression Line
- UK recommends reagents with ISI 1.0 - 1.4
(reduces error seen with insensitive, high ISI reagents)
Name 4 contraindications to warfarin
- Active peptic ulcer
- Pregnancy (can cause bony abnormalities in unborn children- dose dependent)
- Uncontrolled HTN
- Infective endocarditis
Name some non-haemorrhagic side effects of warfarin
- Rash
- Alopecia
- Symptoms of association are common
Describe the epidemiology of AF
More common in men than women
Becoming more common overall: 3 fold increase 1968-1989 (Framingham)
25% paroxysmal
Many have underlying cardiac disease
What are the complications of AF?
Increased risk of stroke and thromboembolism
Increased risk of death
Associated with higher mortality from CHD and HF
Impaired cognition/dementia
What factors would cause a score of 1 (each) on the CHADS2 risk score?
- CHF
- HTN
- Age >75
- Diabetes
- Stroke/TIA
What would cause a score of 1 (each) on the CHA2DS2-VASC risk score?
- CHF or LVEF < or = 40%
- HTN
- Age >75
- Diabets
- Stroke/TIA
- Thromboembolism/ vascular disease
- Age 65-74
- Female
What factors give a score of 1 (each) in the HASBLED risk score?
- HTN >160mmHg
- Abnormal liver/renal function
- Stroke or TIA in the past
- Bleeding disorders
- Labile INR
- Elderly (>75)
- Drugs (aspirin etc), alcohol use
What INR is optimal coagulation control?
Target INR 2.5 with an acceptable range of 2-3
What effect does aspirin have in prevention of stroke in AF patients?
No effect- only effective if AF not present