1. Anticoagulation ACCP guidelines 2012
Megan Chan, PGY-2
UHCMC

2. Coumadin
Inhibits the cyclic interconversion of Vit K in the liver  decrease activation of factors 2,5,9,10
During 1st 2-3 days of initiation, can be hypercoagulable 2/2 coumadin’s effects on Protein C & S
Typically 5mg daily
If outpt can do 10mg x2 day loading dose
Lower dose in elderly, liver dz, poor nutritional status, HF

5. INR monitoring as Outpatient
1st check is after 2-3 doses
Then 2x/wk until INR therapeutic
Then weekly
Then every other week then monthly
Then q3 months if has had 3 months of consistent results
If INR not in desired range can increase or decrease by 5-20% of total weekly dose

7. Unfractionated Heparin
Works by binding to antithrombin to inactivate thrombin (Factor IIa) and Factor Xa
Also prevents growth and potential propagation of clots
Half life: 30mins to 2 hours
Risk of HIT:
Plts decrease by >50% or are <150K after initiation of heparin
Usually 5-14 days after initation

8. LMWH Enoxaparin (Lovenox), Dalteparin (Fragmin)
Increased affinity to Factor Xa relative to thrombin
Therapeutic dosing 1mg/kg q12 hrs or 1.5mg/kg once a day
Avoid in pts with CrCl <30 mL/min and in pts with HIT
Half life: 3-6 hours

9. Fondaparinux (Arixtra)
Specific only to Factor Xa thus low risk for HIT
Recommended for general surgery prophylaxis in pt’s have contraindications to LMWH
SubQ injection
Half life: 18 hours

10. Bivalirudin (Angiox) Reversible direct thrombin inhibitor
Used here at UH for pts you suspect or have HIT
Continuous Drip

11. Dabigatran (Pradaxa) Direct thrombin inhibitor
PO med FDA approved in 2010
Can be used for Afib stroke/embolism prevention
150mg BID, adjust for decreased CrCl
Pros: no monitoring or overlap needed, fewer drug/food interactions
Cons: Short half-life (12-17 hrs), no antidote for reversal

12. Rivaroxaban (Xeralto)
Direct factor Xa inhibitor
PO med FDA approved 2011
Indications:
Tx of DVT/PE & reduce risk of recurrence
DVT prevention in knee/hip replacement surgery
Dosing:
DVT prophylaxis: 10mg daily
Tx DVT or PE: 15mg BID x 21 days then 20mg daily
Afib: 20 mg daily
Adjust for lower CrCl
Half life 5-9 hours

13. Apixaban (Eliquis) Factor Xa inhibitor PO med FDA approved in 2012
Indicated for Afib related stroke or embolism prevention
Dosing:
Typically 5mg BID
lower for elderly, low body weight, CKD
Half life 12 hrs

14. Switch from LMWH or other NOAC
Dabigatran1
(Pradaxa®)
Rivaroxaban2
(Xarelto®)
Apixaban3
(Eliquis®)
Edoxaban4
(SavaysaTM)
Time to peak effect
1 hour (empty stomach)
**Manufacturer requires 5-10 days of parental anticoagulation prior to initiation for treatment of DVT/PE
2-4 hours
3-4 hours
1-2 hours
Switch from UFH
Stop infusion and start dabigatran at the same time
Stop infusion and start rivaroxaban at the same time
Stop infusion and start apixaban at the same time
Stop infusion and start edoxaban 4 hours later
Switch from LMWH or other NOAC
Start dabigatran 0-2 hours prior to next scheduled dose of LMWH/NOAC and omit dose of LMWH/NOAC
Start rivaroxaban 0-2 hours prior to next scheduled evening dose of LMWH/NOAC and omit dose of LMWH/NOAC
Start apixaban at the same time as next scheduled dose of LMWH/NOAC and omit dose of LMWH/NOAC
Start edoxaban at the same time as next scheduled dose of LMWH/NOAC and omit dose of LMWH/NOAC
Switch from warfarin
Stop warfarin and start dabigatran once INR <2.0
Stop warfarin and start rivaroxaban once INR <3.0
Stop warfarin and start apixaban once INR <2.0
Stop warfarin and start apixaban once INR <2.5
References
Pradaxa® [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; Revised January 2015.
Xarelto® [package insert]. Titusville, NJ: Janssen Pharmaceuticals; Revised December 2014
Eliquis®[package insert]. New York, NY: Bristol-Myers Squibb Pharma Company; Revised June 2015.
SavaysaTM package insert]. Parsippany, NJ: Daiichi Sankyo, Inc.; Revised January 2015.
Credits: Sarah Dickey, Pharm D
Louis Stokes Cleveland VAMC

15. VTE Tx initiation: Coumadin + Heparin/Fondaparinux
At least 5 days overlap and until pt’s INR is at least 2.0 for 2 consecutive days
Rivaroxaban approved for tx of DVT or PE
LMWH best for anticoagulation in those with solid tumor-related VTE
½ the risk for recurrent VTE than Coumadin in those with malignancy-related VTE, no effect on mortality

16. Treatment course for VTE
1st provoked DVT or PE: 3 months
1st unprovoked DVT or PE:
3-6 months if low risk for bleeding, then evaluate risk-benefit ratio for extended therapy.
3 months if high risk for bleeding
1st VTE = unprovoked PE:
Life long if low risk bleeding
2nd unprovoked DVT or PE:
Life-long if low-moderate risk bleeding
3 months if high risk bleeding
Recurrent: lifelong therapy
PE with active cancer: life long therapy
Catheter related: 3 months after catheter removed

17. Non-valvular Afib CHA2DS2VASC:
CHF, HTN, Age =1 vs ≥75 =2, DM, Stroke/TIA, Vascular dz
Coumadin, Dabigatran (Pradaxa) & Apixaban (Eliquis)
Afib + Stable CAD (no ACS in past year)—coumadin alone > coumadin + ASA
Intermediate-High risk Afib with ACS –anticoagulant + single antiplatelet for 12 months
Low risk Afib with ACS—dual antiplatelet therapy
High risk Afib with stent placement—triple therapy (anticoagulant, ASA, plavix) for at least 1 month of bare metal, 3-6 months for drug-eluting  anticoagulant + single antiplatelet
Low-Intermediate risk Afib with stent placement—dual antiplatelet therapy > triple therapy for 12 months

18. Cardioversion
If Afib/Aflutter >48 hrs or unknown duration, anticoagulate for 3 weeks prior & 4 weeks post cardioversion

19. Prosthetic valves INR goals: Mechanical aortic valve: 2.0-3.0 + ASA
Mechanical mitral valve: ASA
Mechanical aortic + mitral valve: ASA

20. Hx of Noncardioembolic Ischemic Stroke or TIA
Plavix 75mg daily OR
ASA/ER dipyridamole 25mg/200mg BID OR
ASA (75-100mg daily)
Cilostazole 100mg BID
Stroke/TIA + Afib:
Dabigatran 150mg BID > Coumadin > ASA + Plavix
Often bridge
*Bolded = stronger recommendation

21. Pre-Op/Post-Op
Warfarin should be stopped 5 days before major surgery and restarted hrs post-op
Can bridge with LMW heparin for pts with high risk of thromboembolism
Restart LMWH 24 hrs after

22. CABG Continue ASA Stop plavix 4 days before surgery
If recently had a stent, would defer surgery for at least 6 weeks after placement of bare-metal sent or at least 6 months after placement of drug-eluting stent. If need emergently, then continue dual antiplatelet therapy.

23. References http://www.aafp.org/afp/2013/0415/p556.html