New Oral

Anticoagulants
Guidelines
KAI YAP
What’s wrong with traditional
anticoagulants???
Development

 Traditional anticoagulants have 2 major limitations:

- Narrow therapeutic window of adequate anticoagulation without
bleeding
- Highly variable dose-response, requiring monitoring by lab testing

These limitations have provided impetus for development of other

antithrombotic agents.
3 new oral anticoagulants (NOAC) dagibatran, rivaroxaban, apixaban
listed on PBS.
Mechanism
Dagibatran – direct thrombin inhibitor
Rivaroxaban – factor Xa inhibitor
Apixaban – factor Xa inhibitor
Indications

 1. Prevention of venous thromboembolism in a patient undergoing

total hip or knee replacement

 2. Prevention of stroke or systemic embolism in patients who have

non-valvular atrial fibrillation and has one or more risk factors for
developing stroke or systemic embolism

 3. Rivaroxaban for the prevention of recurrent venous

thromboembolism and for the treatment of deep vein thrombosis
and pulmonary embolism.
Contraindications

 Known hypersensitivity to ingredients of NOAC

 Clinically significant active bleeding
 Renal impairment <30ml/min
 Hepatic disease (child pugh – C)
 Recent high risk bleeding lesion (eg. ICH < 6 months)
 Pregnancy or breast feeding
 Recent stroke, surgery, GI bleed or ulcer
 Recent fibronolytic therapy <10days
 Concomitant warfarin therapy
Features of NOAC

 Features to consider
- Faster onset
- Shorter ½ life
- Less drug-drug interactions
- No need for monitoring with NOACs
- No antidotes
Dosing – Total hip / knee
replacement (VTE prophylaxis)

Dagibatran Rivaroxaban Apixaban

Crcl > 50ml / min 220mg once daily 10mg once daily
Crcl 30–50ml / min 150mg once daily 10mg once daily 2.5mg
once daily
Crcl 15-30ml / min contraindicated contraindicated
Dosing – Non-valvular Atrial
Fibrillation
Dagibatran Rivaroxaban Apixaban
Crcl > 50ml / min 150mg twice daily 20mg once daily
Crcl 30-50ml / min 110mg twice daily 15mg once daily 5mg twice daily
Crcl 15-30ml / min Contraindicated Contraindicated
Special Older than 75 Not applicable At least two of
following:
populations years old -older than 80 yo
110mg twice daily -Weight less than 60kg
-Scr > 133micromol/L

-2.5mg twice daily

Dosing – treatment of DVT / PE

 Rivaroxaban
 Crcl > 30ml / min
 15mg twice daily for three weeks, followed by 20mg daily
Switching anticoagulants

Switching from Switching to Instructions

LMW Heparin NOACs When next dose of LMW
Heparin is due
Heparin NOACs Immediately when heparin
ceased
Warfarin NOACs Start once INR < 2
Dagibatran LMW heparin / UFH No bolus required. Start 12
hrs after last dose
Rivaroxaban / Apixaban LMW heparin / UFH No bolus required. Start 24
hrs after last dose
NOACs Warfarin Continue NOAC and give
warfarin ≤ 5 mg
Stop NOAC once INR ≥ 2 on
2 consecutive days
What do we do when patients
bleed?
Management of bleeding (Initial Ix)

 Seek early haematology advice

 Dagibatran:
 Measure: FBC, U&E, LFT, coagulation profile, Haemoclot and
dabigatran level
 normal TT excludes dabigatran activity
 normal aPTT suggests bleeding not due to dabigatran
Management of bleeding (Initial Ix)

 Rivaroxaban / Apixaban:
 Measure: FBC, U&E, LFT, coagulation profile, anti-Xa and
rivaroxaban level
 normal PT suggests rivaroxaban level not high
 aPTT cannot predict anticoagulant effect
 tests are currently inconclusive for apixaban
Management of bleeding (mild)

 Mild bleeding -
- local haemostatic measures
- delay or discontinue NOAC as required
Management of bleeding
(clinically significant)
 reduction in Hb >20 g/L or requiring RBC transfusion > 2 units
 Stop NOAC therapy
 Give oral charcoal if NOAC ingested < 2 hours ago
 Maintain adequate hydration to aid drug clearance
 Local haemostatic measures: mechanical compression
 Transfusion support: RBC transfusion as per Hb level
 Consider platelet transfusion if on antiplatelet therapy or if platelets
< 50 x 109/L
 Consider radiological and surgical interventions to identify and treat
source of bleeding
Management of life threatening
bleeding
 bleeding in critical area or organ, loss of Hb > 50 g/L, hypotension not
responding to resuscitation

 Get advice of haematologist!!!

 T/f to SCGH or RPH

 a)FEIBA (factor eight inhibitor bypass activity) 25 -100 International

Units/kg, repeat at 12 hours (probably beneficial)
 b)rVIIa 90 microgram/kg every 2-3 hours (possibly beneficial)
 c)prothrombinex – VF 25-50 International Units/kg (if not administered
earlier)
 d)tranexamic acid 15-30 mg/kg IV for mucosal bleeds
Prescribing a new oral
anticoagulant
 1. Lab tests – FBC, EUC, LFTs
Contraindications:
-Poor renal function (CrCl ≤ 30 mL/ min, apixaban: ≤ 15 mL/min)
-Liver disease (e.g. ALT > 3x upper limit of normal)
-Hb ≤ 100 g/L (assess risk vs. benefit)
Prescribing a new oral
anticoagulant
 2. Detailed History
EXCLUSION Criteria:
-Known hypersensitivity to NOAC preparation
-Pregnant or breastfeeding
-Stable warfarin therapy
-Prosthetic heart valve
-Recent stroke
Prescribing a new oral
anticoagulant
 3. Assess bleeding risk
-Disorder of haemostasis
-Recent surgery (≤ 1 month ago)
-GI bleed ≤ 12 months ago
-Ulcer ≤ 30 days ago
-Fibrinolytic treatment last 10 days
-Dual antiplatelet therapy
Prescribing a new oral
anticoagulant
 4. Consider contaminant medications
 Rivaroxaban / apixaban
-Systemic azole antifungals (except fluconazole)
-HIV-protease inhibitors

 Dabigatran
-Systemic azole antifungals (except fluconazole)
-dronedarone
-Simultaneous initiation with verapamil
-cyclosporin and tacrolimus
Prescribing a new oral
anticoagulant
 Is patient on warfarin?
 Stop warfarin
 Start NOAC once INR < 2
Western Australia Therapeutic
Advisory Group Guidelines
 Please visit
http://www.watag.org.au/watag/publications.cfm#guidelines