1. Anticoagulation in the Inpatient Setting
AIMS Morning Report
October 7, 2015
Lindsay Waddington, PharmD
PGY1 Pharmacy Practice Resident

2. Objectives Recall mechanism of action for anticoagulants
Recognize when to adjust dosing for anticoagulant agents (e.g. weight, renal function)
Select optimal anticoagulant agent based on patient specific factors

3. Clotting Cascade http://www.passmed.co.uk/haemostasis.html
Stock image/vs making own and adding drugs

4. Review of Formulary Agents
MECHANISM OF ACTION
MONITORING
Warfarin (Coumadin®)
Vitamin K antagonist
INR, liver function, nutrition (Vitamin K)
Dabigatran (Pradaxa®)
Direct Thrombin (factor IIa) Inhibitor
Renal function (CrCl 30)
Rivaroxaban (Xarelto®)
Factor Xa Inhibitor
Renal function (Tx: CrCl 30, NVAF: CrCl 50), hepatic function
Apixaban (Eliquis®)
Age, weight, SCr
Fondaparinux (Atrixa®)
Renal function (CrCl 50, 30), weight
Enoxaparin (Lovenox®)
Inhibition of Factor Xa and Factor IIa, enhancing antithrombin III
Factor Xa Level , Renal function (CrCl 30)
Unfractionated Heparin
Potentiates antithrombin III (inactivates thrombin)
aPTT
WARFARIN – inhibits formation of vit K clotting factors…..what are they?.... II, VII, IX, X and proteins C + S
½ life ~40 hours = steady state in 120 hours or 5 days – full therapeutic effect in 5-7 days. Metabolized via CYP2C9, 1A2, 3A4, 2C19 – numerous drug interactions. Severe/end-stage renal disease warfarin is anticoagulant of choice (AHA/ACC/HRS jan 2014)
DABIGATRAN – BID dosing, 150mg usual, 75mg if CrCl (RE-LY)
Red flags - >/= 80 years old CrCl 30mL/min
CrCrl <30 and hemodialysis excluded from trials
RIVAROXABAN – CYP3A4, 3A5, 2J2 >15mg/day with food NVAF: CrCl reduce to 15mg (ROCKET, RECORD)
APIXABAN – CYP3A4, pgp, compliance BID dosing (ARISTOTLE, AVERROES) SCr >1.5 but less than 2.5  excluded from studies 2 criteria of the 3
FONDAPARINUX - Fondaparinux prophylaxis 2.5mg (>50kg only), treatment <50kg 5mg/day, 7.5mg if , >100kg then use 10mg
LOVENOX – monitor with Factor Xa level (referred to as heparin level in Sunrise)
HEPARIN – aPTT normal – dependent upon lab/institution
**Monitor signs/symptoms of bleeding/CBC for all agents**

5. Endoxaban (Savaysa®) FDA approved Oct 2014 and Jan 2015
60mg once daily (treatment)
Adjust for weight <60kg
Adjust for CrCl <50mL/min
Contraindicated for CrCl <15mL/min or >95mL/min in atrial fibrillation

6. Clinical cases

7. Case 1: “I’m too sick to get out of bed”
72yo F needs DVT prophylaxis
Prophylaxis
Planned vs. emergent

8. Case 1: “I’m too sick to get out of bed”
72yo F needs DVT prophylaxis (enoxaparin)
Standard dose for prophylaxis 40mg daily
Weight?
42kg : enoxaparin 30mg daily
142kg: enoxaparin 30mg twice daily
Renal function?
Adjust if CrCl <30mL/min
Past medical history?
Therapeutic dose of anticoagulation, drug allergies
Prophylaxis

9. Case 1: “I’m too sick to get out of bed”
Bleed risk?
Anemia, patient status, pertinent labs
Thrombus risk?
Previous venous thromboembolism, recent surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility, severe obesity, known thrombophilic disorder
Pertinent labs INR, CBC

10. Prophylactic Enoxaparin at St. Vincent
Weight <40kg
Heparin 5000 units SQ BID
Weight 40kg - 50kg
CrCl <30mL/min
CrCl >30mL/min
Enoxaparin 30mg SQ daily
Weight 50kg - 120kg
Enoxaparin 40mg SQ daily
Weight 120kg - 180kg
Enoxaparin 30mg SQ BID
Weight >180kg
Enoxaparin 40mg SQ BID
Specifically for medical patients with severely restricted mobility during acute illness
Treatment dosing of lovenox – 1mg/kg/dose Q12 or 1.5 mg/kg daily

11. Case 2 “What’s your OR look like?”
45yo M with a home dose of rivaroxaban 20mg daily with evening meal
Scheduled for a procedure (low bleeding risk) on Friday
How do you manage anticoagulation?
Hold at least 24 hours prior to surgery
Hold at least 24 hours if high risk of bleed hold 2 days
No reversal agent, utilize blood products
Reaches peak plasma conc in 2-4 hours
No need to bridge, if NPO post surgery switch to parenteral
Minor surgery ~2 half lives, major surgery 4-5 ½ lives
anticoag

12. Stopping Anticoagulants for Planned Surgery
Drug
½ Life
When to stop
Warfarin (Coumadin®)
40 hours
5 days prior (or administer vit K dependent upon surgery
Dabigatran (Pradaxa®)
12-17 hours (longer with renal impairment)
CrCl >50mL/min 2 days
CrCl <50mL/min 5 days
Rivaroxaban (Xarelto®)
5-9 hours
(longer in elderly)
At least 24 hours prior to surgery
Apixaban (Eliqis®)
8-15 hours
Fondaparinux (Atrixa®)
17-21 hours
Enoxaparin (Lovenox®)
2-4 times standard heparin/based on Xa activity
12 hours prior for prophylactic doses
24 hours prior for treatment doses
Unfractionated Heparin
60-90 minutes
4-6 hours prior
“in patients who require temporary interruption of a VKA before surgery, we recommend stopping VKAs approximately 5 days before surgery COMPARED to shorter time before surgery”
“In patients who require temporary interruption of a VKA before surgery, we recommend resuming VKA approximately 12 to 24 hours after surgery when there is adequate hemostasis VERSUS later resumption of VKA”
In patients with a mechanical heart valve, afib, or VTE at high risk for thromboembolism - bridge instead of no bridge
low risk for thromboembolism – no bridge
Minor derm, dental (may stop 2-3 days prior), cataract – continue VKA – utilize local hemostasis, continue ASA
ASA - should be held 7-10 days prior if you want it cleared
Clopidogrel/prasugrel stop 5-7 days prior
Stopping UFH 4 to 6 hours before surgery
Therapeutic lovenox stop 24 hour instead of 12 hours prior resume hours post
Xarelto ½ life hours in elderly

13. Case 3: “I’ve been taking this dose of warfarin longer than you’ve been alive”
59yo M MRSA cellulitis (oral agent to better transition home)
Home medication: Warfarin 5mg daily
Antibiotic to cover MRSA outpatient
Sulfamethoxazole-trimethoprim
Doxycycline
Clindamycin
(polypharm) warfarin
What antibiotic covers MRSA outpatient?
Bactrim
Clindamycin
Doxycycline
(Linezolid)
(Minocycline?)

14. Warfarin Warfarin drug interactions ABC’s A: Antimicrobials in general
B: Bactrim
C: Ciprofloxacin (all flouroquinolones)
D: Diflucan (all azole antifungals)
E: Erythromycin (all macrolides)
F: Flagyl
Avoid NSAIDS
Herbals/Vitamin K intake
CYP Enzymes (Phenytoin, Rifampin, Amiodarone)
Alcohol
Bolded drugs empirically reduce warfarin dose
“G”’s - ginko, ginseng, ginger, green tea

15. Key Points
Anticoagulant agents are adjusted based on weight and renal function
Adjusting and/or holding therapy around surgery is drug specific and procedure specific
Medications and disease states can also influence anticoagulation

16. References
Guyatt GH, Akl EA, Crowther M, et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2 Suppl): 7S-47S
January et al AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary. JACC. 2014; 64(21):
Siegal D, Yudin J, Kaatz S et al. Periprocedural Heparin Bridging in Patients Receiving Vitamin K Antagonists: Systematic Review and Meta-Analysis of Bleeding and Thromboembolic Rates. Circulation. 2012; 126:
Coumadin® (warfarin sodium) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2011.
Pradaxa® (dabigatran)[package insert]. Ridgefield, CT: Boehringer Ingelhein; 2015.
Xarelto ® (rivaroxaban) [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2015
Eliquis ® (apixaban) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2015.
Arixtra ® (fondaparinux injection) [package insert]. Mississauga, ON: GlaxoSmithKline Inc.; 2013
Lovenox (enoxaparin) [package insert]. Bridgewater, NJ: Sanofi-Aventis LLC; 2013. 
Savaysa® (edoxaban) [package insert]. Parsippany, NJ: Daiichi Sankyo, Inc.; 2015.
Heparin sodium for injection [package insert]. Kirkland, QC: Pfizer, Inc.; 2014.
Stroke guidelines
Periprocedural heparin bridging in patients receiving vitamin K antagonists : AHA
2014 AHA/ACC/HRS Guideline