IC5: Management of Anticoagulants in VT Disorders Flashcards
Explain how AF can cause stroke
turbulent flow is created by the uncoordinated fibrillation of the left atrium
This causes a concentration of clotting factors in the left atrial appendage (LAA)
When a clot breaks off, it can enter the LV and travel along the aorta towards the cerebral circulation
What is the CHADS-VASc score used for?
To identify patients at low stroke risk who should not be offered antithrombotic therapy and identify patients who should be started on DOACs
What are the components of CHA2DS2-VASc?
C: congestive heart failure → signs and symptoms for reduced LV EF (+1)
H: hypertension → resting BP > 140/90mmHG on at least two occasions or current antihypertensive treatment (+1)
A: age 75 years or older (+2)
D: diabetes mellitus with fasting glucose > 125mg/dl (7mmol/l) or treatment with oral hypoglycemic agents and/or insulin (+1)
S: previous stroke, transient ischemic attack of thromboembolism (+2)
V: vascular disease → previous MI, periperhal artery disease or aortic plaque
A: age 65-74 years (+1)
S: sex category → female (+1)
What are the recommendations for different CHA2DS2-VASc risk scores?
- 0 pts → do not start antiplatelets nor anticoagulants
- 1 pt → do not start antiplatelets, consider anticoagulation based on risk factors (not all are equal) (offer warfarin or DOAC if not contraindicated)
- 2 or more pts → offer warfarin or DOAC if not contraindicated, discuss and address bleeding risk factors and treatment options
What are the factors favouring warfarin use? (4)
- pts who can maintain at least 6/10 INR readings within therapeutic range while on warfafin
- pts unable to tolerate DOAC SEs (such as epigastric discomfort)
- pts with moderate to severe liver or renal impairment
- pts with clinically significant DDIs with DOACs
What are the factors favouring DOAC use? (3)
- pts with less than 6/10 INR readings within therapeutic range while on warfarin
- pts with difficult assess to INR monitoring (eg. venous access or laboratory access)
- pts reluctant to have frequent INR monitoring
What is the HASBLED score used for?
mainly used to identify and modify the modifiable risk factors like treating BP and stopping antiplatelet agents
What are the components of HASBLED?
- H: hypertension SBP > 160mmHg
- A: abnormal renal function (dialysis, renal transplant, SCr > 200micromol/L), abnormal liver function (cirrhosis or bilirubin > 2x ULN or AST/ALT/ALP > 3x ULN) (each oprgan impairment is worth 1 point)
- S: stroke history
- B: bleeding history or predisposition to bleeding
- L: labile INRs (unstable or high INRs or less than 6/10 being within therapeutic range)
- E: elderly (age > 65yo)
- D: drugs (antiplatelets or NSAIDs) or alcohol ≥ 8 units per week
Explain apixaban dosing and the criteria (3) for special dosing
Normally 5mg BD
2.5mg BD if any 2 of the following:
age ≥ 80yo,
weight ≤ 60kg,
SCr ≥ 1.5mg/dL or 132.6 mmol/L [memorise]
Explain edoxaban dosing and the criteria (3) for special dosing
Normally 60mg OD
30mg OD if any 1 of the following:
CrCl 30-50ml/min,
weight ≤ 60kg,
comcomitant verapamil, quinidine, dronedarone
What are the 2 drugs that require dosage adjustment in CrCl 30-50ml/min
Rivaroxaban and edoxaban
What is the drug of choice (and second line) for elderly?
Apixaban (edoxaban second line)
What is the drug of choice in low BW?
Apixaban (edoxaban second line)
What is the drug of choice in high BW?
Rivaroxaban
Which warfarin enantiomer is more active?
S-warfarin
How should wafrarin dose be adjusted in 2C9 polymorphism
More metabolism, therefore needs a. higher warfarin dose
How should wafrarin dose be adjusted in VKORC1 polymorphism
More sensitive, therefore needs a lower warfarin dose
When is warfarin still required (cannot use DOACs) (3)
left ventricular thrombus
prosthetic heart valve
antiphospholipid syndrome-related VTEs
What is the slowest factor to decrease in level?
Factor II
What is the slowest factor to decrease in level?
Factor II
What is hypercoagulable state?
Protein C and S are natural anticoagulants that are reduced by warfarin and confers a hypercoagulable state taking about 4-5 days to ease away (this can be covered with the use of clexane (LMWH enoxaparin brand name)
When should genotype testing for warfarin patients be conducted?
patients taking ≤ 21mg/week or ≥ 49mg/week
Test for VKORC1 and 2C9
Which 2 drugs require preemptive drug adjustment of warfarin
- Bactrim (sulfamethoxazole/trimethoprim) reduce warfarin by 25-50%
- Ciprofloxacin, reduce warfarin by 20-30%
How can lifestyle changes affect CYP450 and INR? (4)
Alcohol binging, inhibits CYP450, increase INR
Chronic alcoholism, induces CYP450, decreases INR
Sudden physical activity, increases metabolism, decreases INR
Smoking, induces CYP450, decreases INR
How can diseases affect INR? (4)
Liver impairment - decreased CF synthesis, increasing INR
Fluid retention - if liver congestion, INR increases; if edematous gut, INR decreases
Fever - higher turnover of CF, INR increases
Hyperthyroidism - higher turnover of CF, INR increases
What is the INR and TTR goal for warfarin patients?
INR of 2.0-3.0 is recommended with an individual TTR (time in therapeutic range) ≥ 70%
What is the INR and TTR goal for warfarin patients?
INR of 2.0-3.0 is recommended with an individual TTR (time in therapeutic range) ≥ 70%
What should warfarin patients with TTR < 70% be switched to?
- recommended to switch to DOACs while ensuring good adherence and persistence with therapy
- Also consider efforts to improve TTR such as education, counselling and more frequent INR checks
