Oral anticoagulation, INR and Stroke Prevention Flashcards

1
Q

Which NOAC drugs are anti factor Xa?

A
  • Edoxaban
  • Rivaroxaban
  • Apixaban
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2
Q

Which NOAC drug is anti factor IIa?

A
  • Dabigatran
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3
Q

Describe the method of action of Warfarin

A
  • 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)
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4
Q

Why does Warfarin not have an immediate effect?

A

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.

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5
Q

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?

A

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.

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6
Q

What factors can influence the effects of warfarin?

A
  • Genetics
  • Diet
  • Adherence
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7
Q

What genetic components influence warfarin sensitivity?

A
  • 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
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8
Q

What genetic components influence warfarin resistance?

A
  • Vitamin K epoxide reductase
  • VKORC1 Asp36Tyr predicts higher dose requirement
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9
Q

What vitamins increase anticoagulation?

A
  • Vitamin E
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10
Q

What vitamins reduce anticoagulation?

A
  • Vitamins K, C, co-enzyme Q10
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11
Q

What herbs increase anticoagulation?

A
  • Garlic
  • Devil’s claw
  • Dong quai
  • Danshen
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12
Q

What herbs reduce anticoagulation?

A
  • Korean ginseng
  • Green tea
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13
Q

What plants reduce anticoagulation?

A
  • St. John’s Wort
  • Broccoli
  • Brussel sprouts
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14
Q

What effects does alcohol have on anticoagulation?

A

Binge drinking increases anticoagulation

Regular drinking reduces anticoagulation

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15
Q

What medications increase anticoagulation?

A
  • Statins
  • Amiodarone
  • Erythromycin
  • Aspirin
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16
Q

What medications reduce anticoagulation?

A
  • Rifampicin
  • Carbamazepine
17
Q

What part of the coagulation cascade can be used to measure the effects of warfarin?

A

Intrinsic pathway

18
Q

What does International Normalised Ratio (INR) measure?

A

Prothrombin time ratio:

Prothrombin time ratio = Patient’s PT(s)

GMN PT (s)

19
Q

In what circumstances is warfarin cautioned?

A
  • History of GI bleed
  • Severe heart failure
  • Liver disease
  • Renal failure
  • Alcoholism
  • Mental impairment
  • Thrombocytopaenia
  • Coagulation disorders
  • Drugs
20
Q

What is the international sensitivity index?

A
  • 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)

21
Q

Name 4 contraindications to warfarin

A
  • Active peptic ulcer
  • Pregnancy (can cause bony abnormalities in unborn children- dose dependent)
  • Uncontrolled HTN
  • Infective endocarditis
22
Q

Name some non-haemorrhagic side effects of warfarin

A
  • Rash
  • Alopecia
  • Symptoms of association are common
23
Q

Describe the epidemiology of AF

A

More common in men than women

Becoming more common overall: 3 fold increase 1968-1989 (Framingham)

25% paroxysmal

Many have underlying cardiac disease

24
Q

What are the complications of AF?

A

Increased risk of stroke and thromboembolism

Increased risk of death

Associated with higher mortality from CHD and HF

Impaired cognition/dementia

25
Q

What factors would cause a score of 1 (each) on the CHADS2 risk score?

A
  • CHF
  • HTN
  • Age >75
  • Diabetes
  • Stroke/TIA
26
Q

What would cause a score of 1 (each) on the CHA2DS2-VASC risk score?

A
  • CHF or LVEF < or = 40%
  • HTN
  • Age >75
  • Diabets
  • Stroke/TIA
  • Thromboembolism/ vascular disease
  • Age 65-74
  • Female
27
Q

What factors give a score of 1 (each) in the HASBLED risk score?

A
  • HTN >160mmHg systolic
  • Abnormal renal function
  • Abnormal liver function
  • Age > or = 65 years
  • Previous stroke
  • Bleeding
  • Labile INRs
  • Polypharmacy
  • Alcohol intake
28
Q

What INR is optimal coagulation control?

A

Target INR 2.5 with an acceptable range of 2-3

29
Q

What effect does aspirin have in prevention of stroke in AF patients?

A

No effect- only effective if AF not present