DIFFICULT CASES: CRACKING THE CODE:

CASE IN POINT: DILEMMAS IN ANTICOAGULATION

MANAGEMENT
SATURDAY/11:30AM-12:30PM

ACPE UAN: 0107-9999-16-038-L01-P 0.1 CEU/1 hr

Activity Type: Application-Based

Learning Objectives for Pharmacists: Upon completion of this CPE activity participants should be able to:
1. Identify situations where anticoagulation management is challenging, such as treatment failure
2. Optimize bridging therapy in patients at high-risk for a bleeding or clotting event
3. Discuss situations where it may be appropriate to extend anticoagulation beyond the
recommended period following a venous thromboembolic event
4. Discuss the available literature surrounding anticoagulant treatment in complex clinical situations
5. Formulate a treatment plan for anticoagulant therapy in a patient with confounding issues

Speaker: Brian Roland, PharmD, BCACP

Brian Roland graduated from Wilkes Universitys Nesbitt School of Pharmacy in 2010. Following
graduation, he pursued his residency training at the Bay Pines Veterans Affairs Healthcare System in
Sarasota, FL. Brians residency training had an emphasis in primary care pharmacy. After completing
his residency, Brian pursued a career in academic pharmacy by accepting a position at Notre Dame
of Marylands School of Pharmacy where he taught cardiovascular medication management in the
ambulatory care setting. In addition to his position at Notre Dame of Maryland, Brian practiced at the
Baltimore Veterans Affairs Healthcare System in a primary care clinic. His disease state management
clinic focused on treating chronic disease such as dyslipidemia, hypertension, diabetes, and heart
failure. He also co-managed an anticoagulation clinic during his time at the Baltimore VA. Following
his time at the school and the VA, Brian pursued a position as a lead clinical pharmacist for Aetna
Medicare. His position at Aetna allows him the opportunity to manage populations to improve
medication adherence and lower risk of high risk medication use in our elderly population. He works
closely with provider groups and hospital systems to help improve these measures through different
clinical interventions.

Speaker Disclosure: Brian Roland reports no actual or potential conflicts of interest in relation to this
CPE activity. Off-label use of medications will not be discussed during this presentation.

FEBRUARY 13, 2016 | IOWA EVENTS CENTER | DES MOINES, IOWA

 "Case: in Point" Dilemmas in
Anticoagulation Management
Brian Roland, PharmD, BCACP

Disclosure
Brian Roland reports no actual or potential conflicts of interest
associated with this presentation

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Learning Objectives
Upon successful completion of this activity, pharmacists
should be able to:
Identify situations where anticoagulation management is
challenging, such as treatment failure
Optimize bridging therapy in patients at high-risk for a bleeding or
clotting event
Discuss situations where it may be appropriate to extend
anticoagulation beyond the recommended period following a
venous thromboembolic event
Discuss the available literature surrounding anticoagulant treatment
in complex clinical situations
Formulate a treatment plan for anticoagulant therapy in a patient
with confounding issues

Case 1 To treat or not to treat

Mr. Jones is a 92 year old WWII
veteran who comes to your
primary care clinic with his wife
for his initial visit. The only
medical records that he has with
him today is a list of his
medications along with all of his
medication bottles. The treating
primary care physician has
asked you to see Mr. Jones to
review his medications and offer
your recommendations.

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Case 1 To treat or not to treat
Physical Exam
No pertinent findings except moderate bruising on right arm
Vitals
BP: 110/65mmHg P: 68bpm Ht: 66in Wt: 110lbs
Medications
Dabigatran 75mg twice daily for atrial fibrillation
Metoprolol tartrate 25mg twice daily for blood pressure/pulse
Atorvastatin 40mg daily for cholesterol
Lisinopril 10mg daily for blood pressure
Memantine XR 28mg daily for memory
OTC Fish Oil 1000mg daily for heart (per patient report)
B-Complex Vitamin daily for energy (per patient report)

Case 1 To treat or not to treat

Questions for the patient:
History of:
Heart or vascular disease (CHF, MI, PAD)
Diabetes
Liver or Kidney Disease
Falls
Major bleeding
Blood Clots or Stroke
Alcohol use
Warfarin use
Chest pain, palpitations, shortness of breath, dizziness, lightheadedness
How does he remember to take his medications?

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Case 1 To treat or not to treat
How did we end up here?
CHADS2 Score: 1 (HTN) + 1 (Age) = 2
CHEST Recommendation: Start anticoagulation therapy

CHA2DS2VASc Score: 1(HTN) + 2 (Age>75) = 3

CHEST Recommendation: Start anticoagulation therapy

HAS-BLED Score: 1 (HTN) + 1 (renal function) + 1 (age>65) = 3

High risk of bleeding

HEMORR2HAGES Score: 1 (HTN) + 1 (renal function) + 1

(Age>75) +/- 1 (Excessive Fall Risk) = 3-4
Moderate to high risk of bleeding

Case 1 To treat or not to treat

How did we end up here?
CHEST Guidelines:
For patients with AF, including those with paroxysmal AF, for
recommendations in favor of oral anticoagulation (including 2.1.9,
2.1.10, and excluding 2.2, 3.1, 3.2, 3.3), we suggest dabigatran 150 mg
twice daily rather than adjusted-dose vitamin K antagonist ( VKA)
therapy (target INR range, 2.0-3.0)
Prescribing Info:
Non-valvular Atrial Fibrillation:
For patients with CrCl 15-30 mL/min: 75 mg orally, twice daily (2.1)

Result: Dabigatran 75mg twice daily for stroke prevention

Chest. 2012;141(2_suppl):e531S-e575S

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Case 1 To treat or not to treat
To treat
Atrial Fibrillation (controlled)
Age (92 years old)
Hypertension (well controlled)

Not to treat
Fall history
Age (92 years old)
Decreased Renal Function (assumed from dabigatran dose)
Memory (evidenced by memantine and forgetting to take
medications)

Case 1 To treat or not to treat

Advanced Age
Increases stroke risk, bleed risk, and fall risk
Controlled Hypertension
Impact on stroke risk varies with control of blood pressure status
Memory
Missed doses may increase risk of thrombosis with NOACs and will
result in difficult to control INR if warfarin chosen
History of Fall
Happened while being active, no other occurrences

Stroke. 2008;39( 5):1482 -1486.

Stroke. 2005;36 (10):2164 -2169.
Eur Heart J . 2007;28(6):752 - 759 .

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 Case 1 To treat or not to treat
Obtain Labs
All labs WNL except:
Hgb: 9.8
SCr: 1.6mg/dL (CrCL: 21mL/min)
Following lab draw, team is unable to stop bleeding from
venopuncture site. Required transfer to acute care facility for
treatment.
EKG: Normal Sinus Rhythm
Plan
Stop dabigatran
Obtain full documentation of atrial fibrillation diagnosis/status
Monitor for signs/symptoms of stroke and report to acute care
facility if any occur

Case 2 A shaky bridge

Mr. Dalio is a 75year old male who is
enrolled in your anticoagulation clinic. He
has been a patient for several years and
is well maintained on warfarin therapy for
atrial fibrillation. He has had a stroke in
the past while subtherapeutic on warfarin
(INR 1.4). His INR in clinic today is 2.7
(Goal:2-3) and has no acute complaints
or changes. He says that he will be going
to get an endoscopy due to severe reflux
and other symptoms in the next month
and wants your help planning his peri-
procedural anticoagulation.

6
Case 2 A shaky bridge
Medications
Rosuvastatin 20mg daily
Metoprolol tartrate 50mg twice daily
Omeprazole 20mg twice daily
Citalopram 20mg daily
Warfarin 5mg daily except 7.5mg Mon/Wed/Fri
Aspirin 81mg daily

Labs: All WNL

Case 2 A shaky bridge

Considerations/Barriers
Renal Function
Normal
Weight
80kg
Ability to inject medications
Wife is on insulin for diabetes, he is caregiver and injects for her daily
Adherence history
Stable on warfarin with good INR history, most likely adherent
Cost
Has prescription insurance, able to afford copay

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Case 2 A shaky bridge
Enoxaparin 1.5mg/kg once daily or 1mg/kg twice daily
Dalteparin 200units/kg once daily or 100units/kg twice
daily
Tinzaparin 175units/kg once daily

Warfarin Enoxaparin Enoxaparin Procedure Enoxaparin Enoxaparin

2/18/16 and warfarin

Case 2 A shaky bridge

Three days following the procedure, you receive a phone
call from the patient updating you on his status:

Had no complications with surgery, but they did remove several

specimens for analysis during the procedure

Started both warfarin and enoxaparin 24 hours after procedure

Report coughing up a dark red substance yesterday and again

today
Describes as dark red, almost brown
Reports no stool discoloration or consistency changes
Worse today than yesterday
Am J Cardio. 2014; 113(4): 662-668.

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Case 2 A shaky bridge
Risk Stratification
Risk of stroke
CHADS2, CHA2DS2VASc Annual estimates of stroke

Risk of bleed
No score needed, patient is actively experiencing post surgical GI bleed
that is worsening

Case 2 A shaky bridge

Risk Stratification
Risk of stroke
CHADS2, CHA2DS2VASc Annual estimates of stroke

Risk of bleed
No score needed, patient is actively experiencing post surgical GI bleed
that is worsening

Short Term Long Term

Clotting Bleeding
Risk Risk
Bleeding Clotting
Risk Risk

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Case 2 A shaky bridge
Stop warfarin, enoxaparin, and aspirin
Consider holding citalopram

When do we restart?

As soon as bleeding stops

One week after bleeding stops
One month after bleeding stops
Three months after bleeding stops

What do we restart?
Warfarin, enoxaparin+warfarin, NOAC

Case 2 A shaky bridge

One month later the member calls you to inform that he
has been switched to rivaroxaban by his primary care
provider. He reports that all has been going well with the
change, but he has to undergo another upper GI
procedure and would like your assistance in planning his
anticoagulation around his procedure.

What do we do different this time around?

Pre-procedure

Post-procedure

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Case 3 INR Roulette
Mrs. Fairfield is a 37 year old
woman who had a DVT 3 months
ago. Upon initial diagnosis, she was
started on enoxaparin and bridged
over to warfarin. This was her first
diagnosed thrombosis, possibly
attributed to estrogen therapy for
birth control, which has since been
stopped. You have been following
her closely in your anticoagulation
clinic. She is excited for todays visit
because she knows it has been 3
months since her DVT.

Case 3 INR Roulette

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Case 3 INR Roulette
Medications
Warfarin 5mg dose adjusted based on INR
Amlodipine 5mg daily for blood pressure
Drosperinone/Ethinyl Estradiol Stopped after VTE event
Physical Exam
Residual swelling in LLE (site of DVT) with minor (3/10) pain and
redness
Ultrasound shows residual venous obstruction
No bleeding/bruising present
Review of Systems
Patient reports nausea/vomiting daily for past week in AM
Labs
All WNL except elevated D-Dimer and HcG (+)

Case 3 INR Roulette

Considerations for continued VTE treatment/prophylaxis
Repeated subtherapeutic INRs during treatment phase
Elevated D-Dimer
Increased risk for recurrent VTE when elevated at time of anticoagulant
discontinuation
Residual Venous Obstruction
Conflicting data
Increased risk for recurrent VTE when present at time of discontinuation
No increase risk for recurrent VTE when present at time of discontinuation
Pregnancy
Increased risk of recurrent VTE

J Thromb Haemost. 2011; 105(5): 837-45

J Thromb Haemost. 2011; 9(6):1119-25.
Blood . 2002; 100 (3:1060-1062

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Case 3 INR Roulette
Therapy Options
Warfarin
Low Molecular Weight Heparin
NOACs

CHEST Recommendations
For pregnant patients, we recommend LMWH for the prevention
and treatment of VTE, instead of UFH (Grade 1B)
For pregnant women, we recommend avoiding the use of oral
direct thrombin (eg,dabigatran) and anti-Xa (eg, rivaroxaban,
apixaban) inhibitors (Grade 1C)

Chest. 2016. doi:10.1016/j.chest.2015.12.005

Case 3 INR Roulette

LWMH Options
Treatment or Prophylaxis
Enoxaparin
40mg every 24 hours
1.5mg/kg every 24 hours or 1mg/kg every 12 hours
Dalteparin
5,000 units every 24 hours
200 units/kg every 24 hours or 100 units/kg every 12 hours
Tinzaparin
175 units/kg every 24 hours
Dose adjusted LMWH to achieve anti-Xa level of 0.2-0.6 units/mL

Data is limited and conflicting in this area

Chest. 2016. doi:10.1016/j.chest.2015.12.005

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Case 4 Cross Check
Mrs. Robinson is a 78 year old female who is a new
patient to your pharmacy. Today is her first visit into the
pharmacy and she asks you to transfer all of her
medications over from the store across town as a result of
her pharmacy network changing. You call the pharmacy
and get the following medications for this patient:
Lisinopril 40mg daily Zolpidem10mg at bedtime
Diltiazem 240mg daily Pantoprazole 40mg daily
Simvastatin 40mg daily Vitamin D 50,000units weekly
Furosemide 40mg daily
Amiodarone 200mg daily
Alendronate 70mg weekly

Case 4 Cross Check

Prior to dispensing the medications, you decide to sit
down and talk with Mrs. Robinson about her medications
and get some more information.
OTC Medications Takes aspirin 325mg daily (self prescribed)

Amiodarone started while she was in the hospital for her fall
Diltiazem started while she was in the hospital for her fall
Fosamax started while she was in the hospital for her fall
Pantoprazole started while she was in the hospital for her fall

Zolpidem has been taking every day for several years

Simvastatin has been taking for over 10 years, no dose changes

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Case 4 Cross Check
Hospitalization
Reports to you that she was walking at the mall and felt like her
heart was beating through her chest. She reports feeling
lightheaded and went to sit down and missed the chair, resulting in
her fall. She states she broke her arm, which is why the hospital
started her on all of these new medications.

Interventions
Simvastatin/Diltiazem drug interaction
Pantoprazole use
Zolpidem use
Aspirin
Need for anticoagulation?

Case 4 Cross Check

Call to the PCP to review interventions
Tells you that episode of atrial fibrillation is what caused her
symptoms leading to her fall. While in hospital, diltiazem and
amiodarone controlled atrial fibrillation and patient back into NSR
upon discharge, so does not want to change diltiazem, but will
change simvastatin to atorvastatin 40mg daily.

Is open to trial of trazodone in place of zolpidem to lower risk of

falls

Agrees to stop pantoprazole

Did not know that patient was taking aspirin 325mg, decrease dose
to 81mg

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Case 4 Cross Check
Need for Anticoagulation
CHF Yes
Hypertension No
Age >75 Yes (78yo)
Diabetes: No
Previous Stroke/TIA: No

Total: 2 = High risk of stroke

Recommend to start anticoagulation, provider agrees and would

like your assistance in choosing the most appropriate agent.

Case 4 Cross Check

Considerations for choosing
Drug Interactions
P-glycoprotein and CYP interactions

Age

Comorbid Conditions

Renal Function

Patient Preference

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Case 4 Cross Check
Dabigatran Rivaroxaban Apixaban Edoxaban Warfarin

Plus

Minus

Summary
The answer is not always written in black and white

There may be more than one correct option for patients

Ideal therapy for patients will change over the span of life

Include the patient in the decision!

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