ic5 (spaf) Flashcards by Nathaniel Chan

How does cardioembolic stroke occur?

During Atrial Fibrillation, turbulent flow in blood causes a concentration of clotting factors in the Left Atrium

Clot forms in the Left Atrial Appendage

Clot dislodges, travel to Left Ventricle, to aorta, to brain

Block blood supply to brain, cause brain tissue death

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What is used to assess if AF patients require OACs?

CHA2DS2VA

Stands for
Congestive HF symptoms
Hypertension
Age at least 75, (+2)
Diabetes
(history of) Stroke, TIA, thromboembolism (+2)
Vascular disease (eg. prev MI, Peripheral artery disease, aortic plaque)
Age 65-74

If score is
0 → no anticoagulants
1 → consider anticoagulants
2 → start anticoagulant therapy

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What does HASBLED stand for?

Hypertension (>160)
Abnormal renal / hepatic function
Stroke (history of)
Bleeding (history of)
Labile INR
Elderly (>65)
Drugs (eg. NSAIDs) or Alcohol

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What is the criteria for dose adjustment in Apixaban? What is the dose with and without adjustment?

Any 2 ABS
Age at least 80
Body weight 60kg or less
SCr > 132.6mmol/L

From 5mg BD to 2.5mg BD

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What is the criteria for Edoxaban dose adjustment? What is the dose?

CBC

CrCl 30-50ml/min
Body weight 60kg or less
Concom Pgpi eg. Verapamil, Quinidine, Dronedarone

From 60mg OD to 30mg OD

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Which DOAC uses Serum Creatinine for dose adjustment

Apixaban

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Which DOAC is indicated for HD in SPAF

Apixaban (although Apix in HD is contraindicated in VTEt)

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Which DOACs are indicated in normal, low, high body weight

All weight: Apixaban

EARA

Low (< 60kg): Edoxaban, Apixaban

High (> 120kg): Rivaroxaban, Apixaban

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DOACs that are
1) CYP3A4 substrates

2) Pgp substrates

1) Rivaroxaban, Apixaban

2) All DOACs (Dabi, Riva, Apix) except Edoxaban

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What are some potent dual inhibitors of CYP3A4 and Pgp? (3 points)

Which DOACs should be avoided with potent dual inhibitors?

Azoles
Ritonavir
Clarithromycin

Rivaroxaban
Apixaban

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What condition is contraindicated with all anticoagulants?

Severe hepatic impairment, as liver cannot produce clotting factors, hence blood will become even thinner if used with anticoagulants

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Which OAC are contraindicated with ESRD?

Which can be used?

Dabigatran (most renally cleared)
Rivaroxaban

Apix can be used in HD (for SPAF)
Warfarin can be used

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Which drugs are contraindicated with Azoles? Why?

Azoles are potent dual CYP3A4 and PGP inhibitors

Dabi: Only Itraconazole and Ketoconazole can be used (i think)
Warfarin: can use, although azoles inhibit cyp2C9 also

Apix and Riva are contraindicated

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When switching from DOAC to Warfarin…

When switching from Warfarin to DOACs…

DOAC to Warfarin: Continue DOAC to bridge initiation of Warfarin (slow onset + hypercoagulability)

Warfarin to DOAC: Stop Warfarin for 3 days and test INR on day 3. If INR < 2, start DOAC

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What is the MOA of Warfarin?

Binding to VKOR, blocking the activation (reduction) of oxidised vitamin K

Reduced Vitamin K serves as a cofactor of gamma glutamyl carboxylase, to produce clotting factors 2, 7, 9, 10

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Genetic polymorphisms of Warfarin and the effect on dose

VKORC1 gene
Polymorphism increases sensitivity to warfarin → require lower dose of warfarin

CYP2C9
Polymorphism increases metabolism of warfarin → need higher dose of warfarin
Eg. Amiodarone, Fluconazole, Metronidazole, Rifampicin

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What happens when Warfarin is initiated?

Clotting factor 7 decreases the fastest (t1/2 = 4-6 hrs)
Clotting factor 2 decreases the slowest (t1/2 = 2-3 days)
Decreases natural anticoagulants (Protein C and S)

Why need LMWH for first 2 days of Warfarin?

1) Slow onset of action
Due to clotting factor 2
INR drop does not reflect actual anticoagulation effect

2) Hypercoagulable state
Due to natural anticoagulants Protein C and S decrease

What are some factors that will affect Warfarin dose? (7 points)

Body surface area
Race
Drug use eg. amiodarone (2C9 inhibitor)
Smoking
Diet
Genetic polymorphism
Antibiotics

Effect of antibiotics on Warfarin?

Need lower dose of warfarin

Bacteria produces menadione (organic Vitamin K) → produce more clotting factors

Antibiotics kill bacteria → Lesser Vitamin K → Lesser clotting factors → Lesser warfarin required

When to do preemptive dose adjustment with Warfarin? (5 points)

Preemptive with CYP inhibitors:

Bactrim: 25-50%
Ciprofloxacin: 20-30%
Metronidazole: 35%
Amiodarone
Fluconazole

When should we monitor INR when starting Warfarin when pt has fever?

When should we do daily monitoring?

3-5 days

Daily if patient is unstable / septic

Warfarin + alcohol

Binge: CYP inhibition, INR ↑
Chronic: CYP induction, INR ↓

how to rmb: liver work overtime in chronic so CYP induction

Warfarin + Physical activity

Increased metabolism, INR ↓

Warfarin + Smoking

Increased metabolism, INR ↓

Warfarin + green leafy vegetables

Higher vitamin K, more clotting factors produced: INR ↓

Warfarin + Liver impairment

Decreased clotting factor synthesis and reduced Warfarin metabolism, INR ↑

Warfarin + Fever

Increased metabolism of clotting factors, INR ↑

Warfarin + Fluid retention

Acute liver congestion, produce lesser clotting factors: INR ↑ Chronic Gut oedema, lower Warfarin absorption in gut: INR ↓ Hence INR will increase before decreasing

Warfarin + Thyroid (hyper, hypo)

HyperTh: Body uses more clotting factors (higher turnover): INR ↑ HypoTh: Body uses lesser clotting factors: INR ↓

Counselling points for Warfarin

Side effects Purple toes, hair loss Look for bleeding If bleeding does not stop after 15 minutes, see a doctor If observe black tarry stools, cough blood or vomit blood, go to the A&E immediately Indication of Warfarin Do not interchange Warfarin brands Compliance to Warfarin is very important Take the dose once you remember If it is more than 8 hours after the missed dose, skip this dose and take the next one instead Inform the doctor if you are planning to conceive as Warfarin needs to be changed to another anticoagulant (LMWH) Diet Do not binge on green leafy vegetables, alcohol Storage Store in a cool dry place, away from sunlight

Indications of Warfarin (5 points)

1) Left Ventricular Thrombus 2) Prosthetic Heart Valve (anywhere in the heart, but only mitral 2.5 - 3.5) 3) Antiphospholipid syndrome 4) Moderate - Severe mitral stenosis 5) Rifampicin, Azoles (Concom use of)

When should patients undergo Warfarin genomics testing?

1) Patients with existing clot eg. Left Ventricular Thrombus 2) Outpatient commencement 3) DDI 4) Questionable adherence

What are the 6 reversal agents?

Fresh Frozen Plasma Prothrombin Complex Conc Vitamin K Idarucizumab, Andexanet Alfa Withhold 1-2 days Dialysis

Reversal agents for Warfarin?

Fresh frozen plasma Prothrombin Complex Concentrates Vitamin K

Which anticoagulants can be reversed by Prothrombin Complex Concentrates?

Riva and Apix can use PCC. Warfarin also Dabi cannot as it directly inhibits prothrombin

Common reversal agents for all DOACs (2 points)

Withhold 1-2 days if renal function normal, non life threatening bleed Idarucizumab, Andexanet Alfa

What is the duration of follow up for SPAF?

Yearly Every 4 months if patient is at least 75yo or frail On dabigatran, edoxaban (CrCl / 10) months if CrCl is 60ml/min or lower

What to monitor for DOACs? Why? (8 points)

1) Full blood count, including haemoglobin Haemoglobin decrease may indicate presence of bleed 2) Renal, liver function Liver: as liver produces clotting factors Renal: for dose adjustments 3) Assess and minimise modifiable risk factors for bleeding Uncontrolled hypertension Medications eg. NSAIDs, aspirin INR (if on Warfarin) Alcohol intake (binge VS chronic) Falls 4) Adherence 5) Assess DOAC choice and dosing 6) DOAC side effects 7) Presence of thrombo-embolism If patient has any signs and symptoms of stroke, DVT, PE 8) Presence of bleeding → identify cause, may need to readjust dose

How to estimate renal function in obese patients?

Calculate CrCl using actual BW and ideal BW Ideal body weight = 0.4 x actual body weight CrCl will be somewhere in the range

What to consider if withholding DOACs in the event of an invasive procedure?

1) Half life of drug 2) Renal function and elimination of drug Eg. if pt need to stop Dabigatran and impaired renal function, hold Dabigatran for 36-48hrs For Apix, Edox, Riva, usually 24hrs unless crcl < 30 then 36hrs 3) Severity of bleeding Only Severe bleeding require reversal agents