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3154 Haematology > IC5 SPAF > Flashcards

IC5 SPAF Flashcards

1
Q

What’s the diff between valvular AF and nn-valvular AF? Which drug would you use for each respectively?

A

Valvular AF vs Non-valvular AF
Valvular AF → use warfarin (DOACs are contraindicated)

  1. Mod-severe mitral stenosis
  2. mechanical prosthetic heart valve

**Non-valvular AF → DOACs
- anything other than 2 mentioned above

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2
Q

What are the consequences of not using ACG to prevent stroke in those with AF?

A

Consequences of un-ACG AF / How does stroke occur in AF?

  • Clots form in the Left Atrial appendage (LAA)
  • Can embolise and travel through the heart and to the brain via the carotid artery
  • Then cause an occlusion → thus ischaemic stroke
  • Can very quickly convert into a brain haemorrhage (if don’t give thrombolytics early / BP too high)
  • Thus need to establish revascularization to brain quickly
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3
Q

What is the drug can you use for SPAF?
What is the drug of choice for SPAF?
What drug should you avoid in SPAF?

A

Drug choices for SPAF:

  1. DOACs (Drug of choice)
    o Greater reduction in risk of ischaemic stroke than warfarin
    o Greater reduction in risk of intracranial haemorrhage than warfarin
    o But need good adherence
  2. Warfarin
    o Target INR 2-3, TTR >70%
    o Warfarin associated with greater deterioration in renal function than DOACs
     Nephropathy
     Vascular calcification
     Glomerular hemorrhage
    Note: Do NOT give antiplatelet for SPAF
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4
Q

What is the treatment plan for SPAF?

A

Treatment plan for SPAF
When patient 1st comes in with AF,
(1) Assess stroke risk using CHA2DS2-VASc

(2) Decide whether or not to give DOACs/warfarin

(3) Assess bleeding risk (ACG SE) using HASBLED + address identified modifiable RF

(4) Discuss with patients

(5) ABC pathway of AF

(6) Follow up and review Counselling, monitoring and follow up plans for SPAF

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5
Q

How do you assess stroke risk for SPAF?
Which step is this in treatment plan for SPAF?

A

(1) Assess stroke risk using CHA2DS2-VASc
CHA2DS2-VA

  1. Congestive HF
  2. HTN >140mmHg x2
  3. Age >=75y/o
  4. Diabetes mellitus
  5. Stroke (history of) / Transient Ischaemic Attack (TIA) / VTE
  6. Vascular disease e.g. MI, peripheral artery disease
  7. Age 65-74y/o

Algorithm:
IF 0pts – DO NOT give ACG/antiplatelets
IF 1pt – consider DOACs
IF 2pts – Give DOACs/warfarin

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6
Q

How to assess bleeding risk for SPAF?
Which step is this in the treatment plan for SPAF?

A

(3) Assess bleeding risk (ACG SE) using HASBLED + address identified modifiable RF
HASBLED

  1. HTN > 160mmHg
  2. Abnormal renal/hepatic function
  3. Stroke (history of)
  4. Bleeding (history of / predisposition to)
  5. Liable INR (unstable, <6/10 INR readings within range)
  6. Elderly (>65y/o)
  7. Drugs e.g. antiplatelets, NSAIDs, alcohol

Note: HASBLED should NOT determine whether or not to stop ACG

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7
Q

What is the ABC pathway of SPAF?
Which step is this in the treatment plan of SPAF?

A

(5) ABC pathway of AF

  1. Avoid stroke
  2. Better AF symptom control (rate & rhythm)
  3. Cardiovascular / comorbidities / other RF e.g. HF, HTN, DM, cardiac ischaemia. Sleep apnoea, obesity
    a. E.g. lifestyle changes, weight loss, regular exercise, reduce alcohol
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8
Q

When is the 1st follow up?
What to do and labs during the 1st follow up?
When is the next follow up and based on what criteria?

A

(6) Follow up and review Counselling, monitoring and follow up plans for SPAF
1st TCU – in 1 month
Look at:

  1. Adherence – re-educate, inform that any minor bleeding do not stop meds
  2. Thromboembolism
  3. Bleeding events – look for reasons, treat, prevent
  4. ADR – mainly bleeding
  5. Co-medications – antiplatelets(aspirin), NSAIDs
  6. Blood sampling – S&S, Hb, renal panel, coagulation panel
  7. Reassessment of CHADS-VA and HASBLED + Address modifiable RF
    – e.g. uncontrolled HTN, meds that predispose pt to bleeding, falls, excessive alcohol
  8. Reassess DOAC and dosing
  • Determine next TCU/blood sampling:
    o Usually – every 1 year
    o >75y/o, frail esp. on dabigatran – every 4 months
    o CrCL<60mL/min – “CrCL/10” months
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9
Q

How to manage patients who bleeds while on DOACs?
What should we do after manging the bleed?

A

Management of bleeding in patients taking DOACs (During bleed)
Think about severity of bleed

  1. Mild bleeding
    a. Wait
  2. Non-life-threatening major bleed
    a. Supportive measures + reversal agent e.g. idarucizumab
  3. Life-threatening major bleed
    a. Reversal agent e.g. idarucizumab(dabi), andexanet alfa(-xaban)
    OR PCC/aPCC

If patient has a high risk of major bleed after doing HASBLED risk score: (After bleeding event)
- Identify cause of bleeding
o IF known and treatable → restart DOAC
o IF unknown/untreatable/irreversible → no treatment / LAA occlusion / watchmen device implanted at LAA

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10
Q

What to do for patients on DOACs who have an unplanned surgery?

A

DOACs in unplanned surgery
1. Acute emergency procedure – use reversal agent
2. Urgent procedure/expedite procedure – if high risk, then hold off DOAC (depending on t1/2 and renal impairment) /reversal agent; if not high risk, then continue DOAC

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11
Q

What is the dosing for Apixaban in SPAF?
What is the renal dose adjustment in SPAF?

A

Apixaban
PO 5mg BD
PO 2.5mg BD
*IF meet 2 out of 3 criteria:
1) >=80y/o
2) BW<=60kg
3) SCr >=132.6mmol/L

Renal dose adjustment for SPAF:
CrCL 30-50mL/min: Same as above
15-29mL/min: PO 2.5mg BD
<15mL/min: Same as above

DDI:Avoid use with dual inhibitors/ inducers

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12
Q

What is the dosing for all 4 DOACs in SPAF?

A

Dabigatran:
PO 150mg BD
PO 110mg BD
(IF >80y/o, use Pgp inhibitor, High bleeding risk)

Rivaroxaban: PO 20mg QD

Apixaban:
PO 5mg BD
PO 2.5mg BD
IF meet 2 out of 3 criteria:
1) >=80y/o
2) BW<60kg
3) SCr =132.6mmol/L PO

Edoxaban:
60mg QD
PO 30mg QD
IF meet any 1: CrCL<30mL/min,
Weight <60kg, concomitant use of verapamil, quinidine, dronedarone

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13
Q

What is the CrCL where Dabigatran contraindicated?

A

15-29mL/min

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14
Q

What is the CrCL when Rivaroxaban is contraindicated?

A

<15mL/min

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15
Q

What CrCL where Edoxaban is not recommended?

A

<15mL/min

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16
Q

What is the renal dose adjustment for all 4 DOACs?

A

Look at pg 83 of words notes

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17
Q

How do you estimate the renal function for renaldose adjustment of DOACs in SPAF?
What body weight to use for different weights?

A

Estimate renal function:

  • Calculate CrCL using Cockcroft Gault Equation
    o [1.23(140-age)weight(0.85 if female)] / SCr
    o Underweight – use TBW
    o Normal weight – use IBW
    o Overweight – use AdjBW
    o Morbidly obese – use TBW & IBW to estimate CrCL range
    o TBW used for DOAC dosing
  • Dosing of drugs in early stages of CKD, SCr NOT suitable, use GFR
  • CKD-EPI (GFR) is used for CKD staging
  • MDRD4 (GFR) and CKD-EPI (GFR) underestimates renal function in elderly
  • MDRD4 overestimates compared to CG when GFR<60
  • Convert GFR to CrCL:
    o CrCL = GFR x BSA/1.73
18
Q

When to use/not to use DOACs in CKD patients for SPAF?

A

Use of DOACs in CKD & AF patients:

  1. CrCL >30mL/min – DOACs
  2. CrCL 15-30mL/min – Consider risk/benefit before giving DOACs  OR LAA occlusion
  3. CrCL < 15ml/min – do NOT give DOACs unless Dr and patient want it  OR LAA occlusion
19
Q

What are some considerations when treating elderly for SPAF?
What meds would you give for elderly for SPAF?

A

Considerations in Elderly for SPAF

  1. Dementia – Ability to understand, administration and adherence issue
  2. Falls and frailty
    a. Rapid deterioration of renal function
    b. Risk of falling < benefits of using warfarin → do NOT withhold DOACs/warfarin due to fall reasons
  3. DOACs e.g. Apixaban/Edoxaban preferred over warfarin
    a. Less intracranial hemorrhage
    b. Less stroke / systemic embolism
    c. Less major bleeds
20
Q

What meds would you give for extreme body weights for SPAF?

A

Considerations in Extreme Body Weight for SPAF
1. Normal Body weight (60-120kg) – All DOACs
2. Underweight (<60kg) – Apixaban, Edoxaban (both need to lower dose)
3. Severely overweight (>120kg / BMI>40) – **Rivaroxaban, Apixaban **
*Since apixaban can be used for all weights in SPAF, give Apixaban

21
Q

What are the DDI for DOACs?

A

DDI impact on DOACs dosing
All are Pgp substrate
All are CYP3A4 substrate except for Dabigatran
Look out for:
- Pgp inhibitors e.g. verapamil, quinidine, macrolides, azoles
- Dual inhibitors of Pgp and CYP3A4 e.g. Azoles, ritonavir, clarithromycin
o Clarithromycin can switch to azithromycin
- Dual Inducers of Pgp and CYP3A4 e.g. Rifampicin, anti-seizure drugs (CBZ, PNY, PHB), St John wort
o Rifampicin is CONTRAINDICATED with DOACs → use warfarin
 Switching from DOAC to warfarin (use DOAC like LMWH to bridge)
* Continue DOAC AND start warfarin till INR >=2
* After 3-5days of starting warfarin, measure INR before DOAC intake:
* IF INR <2, continue DOAC (Edoxaban is half dose)  measure INR 1-3 days later  stop DOAC when INR>=2
* IF INR>=2, stop DOAC and measure INR 1 day
 Since there is also interactions between warfarin and rifampicin, need to give higher dose of warfarin
o Anti-seizure meds & DOACs
 Dabigatran CONTRAINDICATED with CBZ/PNY/Valproic acid
 Rivaroxaban CONTRAINDICATED with CBZ/PHB/PNY/Valproic acid
 Apixaban & Edoxaban CONTRAINDICATED with Valproic acid
o St John’s wort CONTRAINDICATED with DOACs
- Antiplatelet effect e.g. gingko, ginseng
Drug-Host Interaction – age, weight, bleeding risk of patient, concomitant use with other drugs

22
Q

What are the CI of dabigatran and riva/apixaban?

A

Contraindications:
Dabigatran
1. Ketoconazole, itraconazole
2. Severe hepatic dysfunction, especially with coagulopathy
3. ESRD
4. Prosthetic heart valve

Riva/Apixaban
1. Azoles (fluconazole impact unknown)
2. Severe hepatic dysfunction, especially with coagulopathy
3. Apixaban maybe used in HD (ESRD)
4. Prosthetic heart valve

23
Q

What are the CI in Dabigatran, Riva/Apixaban and warfarin? (5)

A

look at pg86 on words note

24
Q

Which warfarin enantiomer is more active and which enzyme is it most metabolized by?

A

S-enantiomer more active AND metabolised by CYP2C9

25
Q

What can warfarin be used for? (5)

A

When is warfarin used?

  1. Left ventricular thrombus
  2. Prosthetic heart valve
  3. Antiphospholipid syndrome-related VTEs
  4. End stage renal disease
  5. Aged >80
26
Q

What is the INR target for different indications?
What is the duration of treatmetn

A

INR target: 2.5(2-3)
DVT 3 months, consider extend
PE 3 months, consider extend
SPAF Lifelong
Valvular heart disease (Severe MS) Lifelong
Bioprosthetic heart valve 3-6 months
Left ventricular thrombus 3 months, TTE to document resolution

INR target: 3(2.5-3.5)
Mechanical heart valve Lifelong

27
Q

Why is there a need for bridge ACG when giving warfarin for both VTE and SPAF?

A
  • Factor II – longest t1/2 (42-72hrs)
  • Factor VII – shortest t1/2 (4-6hrs)
  • Sometimes INR reach 2, does NOT mean that patient is sufficiently anticoagulated
  • Reasons to give loading dose:
    o to reach target INR faster (if not, only reach target INR within 3-4days)
    o when have existing clot / have AF, want them to get out of hospital faster
    - Warfarin inhibits production of Protein C & S (endogenous ACG) → thus causing hypercoagulable state for 4-5days
    o Thus give clexane (enoxaparin) when give high dose warfarin (regardless of indication, meaning for both VTE and SPAF)

VTE - immediately prevent growth of thrombus clot
SPAF - overcome the hypercoagulable state

28
Q

Which clotting factors, indirectly reduced by warfarin, have the shortest and longest t1/2?

A
  • Factor II – longest t1/2 (42-72hrs)
  • Factor VII – shortest t1/2 (4-6hrs)
29
Q

What are the reasons for giving loading dose warfarin?

A

Reasons to give loading dose:
- to reach target INR faster (if not, only reach target INR within 3-4days)
- when have existing clot / have AF, want them to get out of hospital faster

30
Q

How is maintenance dose achieved?

A

How is maintenance dose achieved?

  1. Do INR, adjust dose, repeat INR and adjust dose alot of TCU
  2. Pharmacogenomics
    a. To reduce no. of admission and discharge earlier (but NOT length of stay)
    b. Good for those with high risk of stroke
    c. Good for those who requires <21mg/week or >49mg/week
    d. Don’t genotype everyone since genetic factors only play some part in interindividual differences in warfarin response
    e. VKOR and CYP2C9 polymorphism
    f. Indians require higher dose of warfarin maintenance dose (becos of VKORC1) [7mg/day]
    g. Done when:
    i. LVT
    ii. Outpatient commencement
    iii. DDI
    iv. Questionable adherence
31
Q

What are the DDI with warfarin? (9)

A

Drug-drug interaction with warfarin
PK (ADME)

  • Absorption from gut
  • Protein binding e.g. NSAID
  • CYP450 inhibitor and inducer
    o CYP2C9 inhibitor e.g. amiodarone, fluconazole, metronidazole, valproic acid
     Azoles, monitor INR (Fluconazole is worse than other azoles)
     Amiodarone has long t1/2 → inhibit > 1 metabolizing enzyme
     In peptic ulcer disease, changed metronidazole to PPI, TCU in 2weeks
    o CYP2C9 inducer e.g. CBZ, PHB, rifampicin, St John’s wort
  • Pgp transporter proteins
    PD (at site of action)
  • Antiplatelets
    Antimicrobials
  • Gut microbiome produces vit K
  • Antibiotic use will kill gut microbiome → less vit K produced and thus less absorbed → less coagulation occur thus → INR increase, not becos of the warfarin drug but becos of less vit K
  • Adjust dose pre-emptively for:
    o E.g. Bactrim (sulfamethoxazole/trimethoprim) → reduce dose by 25-50%
    o E.g. Ciprofloxacin → reduce dose by 20-30%
    Extra note:
  • INR increases in febrile states (e.g. when you have an infection, get fever) becos of increase turnover rates of clotting factors (rather than warfarin effect)
  • Thus repeat INR 3-5 days after starting therapy. Consider daily INR if admitted and unstable/septic.
  • Do NOT dose adjust immediately on the 1-3 days
32
Q

Why does INR increase in febrile state? What should you do?

A
  • INR increases in febrile states (e.g. when you have an infection, get fever) becos of increase turnover rates of clotting factors (rather than warfarin effect)
  • Thus repeat INR 3-5 days after starting therapy. Consider daily INR if admitted and unstable/septic.
  • Do NOT dose adjust (reduce) immediately on the 1-3 days
33
Q

What are the drug-lifestyle interactions with warfarin?

A

Drug lifestyle interaction
1. Acute alcohol binge – CYP450 inhibitor → ↑ INR
2. Chronic alcohol – CYP450 inducer + Increase warfarin metabolism → ↓ INR
3. Exercise – Increase warfarin metabolism → ↓ INR
4. Smoking – CYP3A4 inducer + Increase warfarin metabolism → ↓ INR

1 increase, 3 decrease

  1. Chronic alcohol – CYP450 inducer + Increase warfarin metabolism  decrease INR
    o Alcohol makes INR control challenging  thus use DOAC (preferably Rivaroxaban/Apixaban, Dabi/Edoxaban need to use LMWH first)
     Switch from warfarin to DOAC
    * Measure INR today
    * IF INR >3, stop warfarin, re-measure INR in 3 days  IF INR still >3, repeat INR next day while continuing both, then decision based on 3rd INR
    * IF INR 2-2.5, start DOAC today or tomorrow & stop warfarin
    * IF INR <2, stop warfarin & start DOAC immediately
34
Q

What to do when patient on warfarin likes to drink alcohol? Under than cutting down on alcohol.

A
  1. Chronic alcohol – CYP450 inducer + Increase warfarin metabolism → decrease INR
    o Alcohol makes INR control challenging  thus use DOAC (preferably Rivaroxaban/Apixaban, Dabi/Edoxaban need to use LMWH first)
    → Switch from warfarin to DOAC
    * Measure INR today
    * IF INR >3, stop warfarin, re-measure INR in 3 days → IF INR still >3, repeat INR next day while continuing both, then decision based on 3rd INR
    * IF INR 2-2.5, start DOAC today or tomorrow & stop warfarin
    * IF INR <2, stop warfarin & start DOAC immediately
35
Q

What are the drug-disease interaction with warfarin

A

Drug disease interaction

  1. Liver disease – ↓ clotting factor production → ↑ INR
  2. Fever – ↑ clotting factor turnover → ↑ INR
  3. Fluid retention (due to liver congestion) → ↑ INR
  4. Fluid retention (due to HF/missed dialysis/renal impairment) → ↓ INR
  5. Hyperthyroidism ↑ clotting factor turnover → ↑ INR
  6. Hypothyroidism → ↓ INR
36
Q

What are the drug food interactions with warfarin?

A

Drug-food interaction: vitamin K
- Have a controlled constant intake of food containing vit K e.g. dark green vegetables, cereal
- Do NOT avoid taking food containing vit K → will have trouble stabilising warfarin as INR can become erratic

37
Q

What are the CI with warfarin?
Compare with Darbigatran and ARiva/Apixaban.

A

Contraindication with warfarin
- Severe hepatic dysfunction (esp. when Child Pugh’s score >C), especially with coagulopathy

2nd part look at pg 85 of word notes

38
Q

What do you do when
INR >4.5,
INR 4.5-10,
INR>10,
minor bleeds and
major bleeds?

A

Warfarin reversal
INR <4.5 – repeat INR, re-dose warfarin
INR 4.5-10 – withhold warfarin, repeat INR, re-dose warfarin, can consider PO vit K 1-2mg
INR >10 – withhold warfarin, give PO vit K 1-2mg
Minor bleed – consider withhold warfarin and/or give PO vit K 1-2mg
Major bleed – withhold warfarin, give IV vit K 5-10mg
**Too high vit K dose e.g. 10mg is associated with delayed re-anticoagulation (~3weeks)
–> high thrombogenic risk

39
Q

What is the drug and dose for warfarin reversal?

A

give PO vit K 1-2mg

40
Q

What happens when too high vit K (10mg) is given as a reversal agent for warfarin bleeding?

A

Too high vit K dose e.g. 10mg is associated with delayed re-anticoagulation (~3weeks)

41
Q

What are the actions/reversal agents for Dabigatran, Riva/Apixaban and warfarin?

A

Dabigatran
1. if renal function normal, non-life threatening bleed
 Withhold 1-2days
2. Urgent case → give idarucizumab
3. Others → dialysis

Rivaroxaban/apixaban
1. if renal function normal, non-life threatening bleed
→ Withhold 1-2days
2. Urgent case → give Andexanet alfa
3. Others → Prothrombin complex concentrate (PCC)

Warfarin
1. Urgent case → PCC
2. May consider → Give vitamin K / Fresh frozen plasma

3154 Haematology (8 decks)

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