Anticoagulation Issues at University
Hospitals Case Medical Center
AKA – ALMOST everything you need
to know for successful AC
management
Teresa L. Carman, MD
Director, Vascular Medicine
Case Medical Center
Pager 33515
Office 41261
Discussion
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Use of the heparin protocol
Anti-Xa assay vs. aPTT monitoring
Anticoagulation quality measures
Safe warfarin dosing
Safe discharge of patients
Anticoagulation monitoring service
referrals
Heparin Order Set
IV Heparin Protocol
• Diagnosis / Weight Based Dosing
 Low intensity dosing
• ACS, Stroke

High intensity dosing
• VTE, CVT, Afib
• Nurse Driven Titration
 Titration table based on 4 hr anti-xa lab value
obtained after initial dosing or titration changes
 With the change in monitoring the titration table
will change to reflect a 6 hr interval for required
titrations
IV Heparin Protocol
• Full Protocol Includes:
Initial
Loading Bolus
Titrated
Drip – know the drip rate
Additional
(Repeat) Bolus (as required)
IV Heparin Protocol
Ordering
Choose the “Loading Dose” to order
the initial bolus
IV Heparin Protocol Ordering
Choose “Continuous Infusion” to order
the drip
• Includes standard nurse driven
titration protocol
IV Heparin Protocol Ordering
Choose the “Repeat Bolus” for
nursing to give a bolus based on Q 4
hr aPTT (anti-Xa) lab value
X
IV Heparin Protocol
Why order the full protocol?
Clinical Results:
• If the full protocol is NOT ordered
 39 hr average time to therapeutic
• Full protocol ordered
 11 hr average time to therapeutic
• All patients were either therapeutic or
supratherapeutic within 6 hrs
IV Heparin Protocol
Why the 4 hour dosing change to the protocol?
• With a 6 hour protocol it usually takes 8 hours between
dose adjustments
• The 4 hour protocol should decrease this interval to
approximately 6 hours
• This should allow patients to a reach consistent
therapeutic range sooner thus impact the risk for recurrent
events
aPTT VS. Heparin Assay
Monitoring
Overview of aPTT
• The aPTT is used in most clinical laboratories to monitor
coagulation and specifically monitor anticoagulants ie.
intravenous unfractionated heparin and direct thrombin
inhibitors
• Clinicians have familiarity with assay
• Readily automated
• Current targets were established based on data from a
post-hoc analysis of a 1972 study which suggested 1.52.5 times aPTT control reduced risk the of recurrent
thromboembolism
Eikelboom JW. Thromb Haemost 2006;96:547-52.
Francis JL. Pharmacotherapy 2004;24:108S-19S.
Disadvantages of Using aPTT
to Monitor Heparin
• aPTT has variable a response to heparin determined by
the different coagulometers and the reagents
 There is no aPTT “standard”
 When the tissue thromboplastin lot changes, a new
therapeutic range needs to be established for the new
lot of reagent
• Test may be affected by numerous factors other than
heparin concentration
 Baseline elevated aPTT makes titration difficult and
inaccurate
Eikelboom JW. Thromb Haemost 2006;96:547-52.
Francis JL. Pharmacotherapy 2004;24:108S-19S.
Conditions that May Prolong
the Baseline aPTT
• Lupus anticoagulants
• Other antiphospholipid antibodies
• Prekallikrein, High Molecular Weight
Kininogen Level
• Low levels (<40%) of:
 Fibrinogen
 Prothrombin
 Factors V, VIII, IX, X, XI, and XII
Eikelboom JW. Thromb Haemost 2006;96:547-52.
Francis JL. Pharmacotherapy 2004;24:108S-19S.
Current Recommendations
from CHEST Guidelines
• Each coagulation laboratory determines the
therapeutic range for their aPTT reagent that
correlates with a heparin assay level of 0.3 to 0.7
international units (IU)/mL (by anti-Factor Xa
assay)
• Each laboratory must determine its own
therapeutic range for heparin for the aPTT
whenever the aPTT reagent changes or with a
change in instrumentation
 Therefore, the range changes almost annually
Hirsh J. Chest 2008;133:141-59
Monitoring
Update on Monitoring
• As of summer 2011 the “aPTT” is not available for
monitoring IV unfractionated heparin therapy at University
Hospitals Case Medical Center. (no correlations have been
done; no target range exists)
• The “aPTT” has been replaced by anti-Xa monitoring using
the “heparin assay, UFH”
• The use of the “heparin assay, UFH” will standardize IV
unfractionated heparin monitoring and make the use of the
aPTT inaccurate
Heparin Assay
• Specifically determines anticoagulant activity of IV
unfractionated heparin by measuring ability of heparinbound antithrombin to inhibit a single enzyme
• More specific than aPTT since it measures inhibition of a
single enzyme
• Major advantage is lack of biologic factors that affect its
result
Eikelboom JW. Thromb Haemost 2006;96:547-52.
Francis JL. Pharmacotherapy 2004;24:108S-19S.
Comparison of Monitoring with
aPTT vs. Anti-Factor Xa Assay
• Prospective, single-center study
1.8
P<0.0001
1.6
• 268 patients on IV heparin for
variety of indications
1.4
1.2
P<0.0001
1
• Utilizing anti-Factor Xa assay
led to fewer tests and dose
adjustments
N=
APTT
0.8
0.6
0.4
0.2
• Cost increase of $1.09/day
more using anti-Factor Xa assay
Anti-Factor Xa
Assay
0
Monitoring
Tests/24 hours
Dosage
Changes/24
Rosborough TK. Pharmacotherapy 1999;19:760-66.
Current “High-Intensity Therapeutic Heparin”
Anticoagulation Orders Using Heparin Assay for
Adult Patients (VTE etc)
Current “Low-Intensity Therapeutic Heparin”
Anticoagulation Orders Using Heparin Assay
for Adult Patients (ACS, stroke)
No Changes for the Monitoring of Other
Anticoagulants
• Prothrombin time/INR is still used to
monitor warfarin
• Therapeutic monitoring of direct thrombin
inhibitors (bivalirudin and argatroban) still
use the aPTT
• Special monitoring for enoxaparin
(Lovenox®) is done by Heparin assay,
Lovenox
Summary #1
• UH uses the heparin assay, UFH for monitoring all
intravenous unfractionated heparin therapy.
• The order set will change to reflect the therapeutic
ranges for “High-dose” and “Low-dose” indications
 “high-dose” anti-Xa = 0.3-0.7 IU/ml
 “low-dose” anti-Xa = 0.3-0.6 IU/ml
• The time between adjustments and monitoring will
decrease to 4 hours in an effort to shorten the time to
therapeutic
Anticoagulation Core Quality
Measures
What are Core Measures ?
• Evidence based clinical measures that
assess quality of care
•
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Impact large populations of patients
Tracks outcomes over time
Framework to rate healthcare performance
Publicly reported
Comparison data available
Currently used in pay for performance
initiatives
4/8/2015
University Hospitals Case Medical Center
Quality Assurance/Peer Review Report Privileged Pursuant to O.R.C. Section 2305.24, .251, .252
25
Where is Data Publicly Reported?
• Hospital Compare www.hospitalcompare.hhs.gov/
• The Joint Commission www.qualitycheck.org
• Ohio Department of Health www.odh.ohio.gov
• Leapfrog www.leapfroggroup.org
• Health Grades www.healthgrades.com/
4/8/2015
Quality Assurance/Peer Review Report Privileged Pursuant to O.R.C. Section 2305.24, .251, .252
VTE Core Measure
• New Core Measure for 2013
• Includes:
• VTE prophylaxis within 24 hours of arrival
• ICU VTE
• Incidence of potentially preventable VTE
• Platelet monitoring for unfractionated heparin
• Anticoagulation overlap therapy
• Comprehensive discharge instructions
• Also part of Meaningful Use
Anticoagulation Committee
•Approach
– Fit compliance into current clinician workflow
• No additional resources
• No retrospective chart abstraction
Basic Essentials
1. All patients require DVT prophylaxis screen on
admission
2. The proper prophylaxis is ordered or an
appropriate reason for omission is documented
Hospital acquired VTE is considered a “never event”
3. VTE treatment transition must meet current
guidelines and this is documented and
supported by the discharge orders
VTE Quality Measure
• To meet certain care standards to prevent
and treat DVT/PE
• Must complete the DVT Risk Assessment
Screening on admission
 Helps
determine DVT risk: low, moderate,
high or very high
– Includes orders based on risk score for both
pharmacologic and mechanical prophylaxis
– Be sure to enter omission reason if choosing not to
order prophylaxis
Deep Vein Thrombosis Risk
Screening
Deep Vein Thrombosis Risk
Screening
Deep Vein Thrombosis Risk
Screening
Deep Vein Thrombosis Risk
Screening
Deep Vein Thrombosis Risk
Screening
Deep Vein Thrombosis Risk
Screening
Summary #2
• All patients are risk stratified on admission
• All patients have prophylaxis ordered – or
– a specific indication for not ordering
prophylaxis is required.
UFH, LMWH, Fondaparinux
Overlap with Warfarin to a
Therapeutic INR
Rational for a 5 Day Overlap and
Discharging Patients on Warfarin
Anticoagulation Caveats
• When short-acting parenteral anticoagulants are
chosen as the starting therapy a minimum of 5 days
of overlap between parenteral, short-acting drugs
and warfarin is required to complete anticoagulation


Unfractionated heparin (UFH)
LMWH
• Lovenox/enoxaparin, Fragmin/dalteparin, Innohep/tinzaparin

Fondaparinux (Arixtra)
• The target INR is typically 2.5 (range 2-3)
• The INR must be > 2 on 2 consecutive days before
stopping the parenteral agent
Warfarin
Anticoagulant effect (VII, IX)
vs.
Antithrombotic effect (X, II)
Anticoagulant effect can be seen within 2 days
Antithrombotic effect takes minimum of 4-5 days due
to the t ½ of prothrombin (24-48 hours)
Parenteral Anticoagulant to
Warfarin Conversion
• The anticoagulant effect of warfarin on the INR
can be seen within 2 days of initiating warfarin
therapy.


Laboratory prothrombin time effect due to FVII
depletion
Does not equate to therapeutic anticoagulation
• The antithrombotic effect of warfarin takes
minimum of 5 days overlap between the drugs.

Minimum time required to achieve a therapeutic level
of anticoagulation and reliable thrombin depletion
Warfarin Effects
• Water soluble, readily
absorbed from the GI
tract
• Interferes with Vitamin
K dependent γcarboxylation

Coagulant factors
• II, VII, IX, and X

Anticoagulants
• protein C and S
How Does Warfarin Work?
• Warfarin inhibits the production of active
clotting factors in the body
 Inhibits
the activity of Vitamin K
• Does not effect the activity of clotting factors
that have already been made by the body
 May
take several days to see effects
 Need overlap therapy with an immediate acting
anticoagulant if rapid response is desired
• Heparin, Lovenox, Arixtra
Parenteral Anticoagulant to
Warfarin Conversion
• Due to the long half-life of prothrombin
(60-72 hours) and the need to fully delete
preformed circulating thrombin and
replace it with terminally modified
prothrombin protein the minimum time to
complete anticoagulation is 5 days.
• INR rises before this time DO NOT reflect
therapeutic anticoagulation.
Summary
• FVII is a vitamin K
dependent protein
• It has the shortest t½ of all
the vitamin K dependent
coagulant proteins
• FVII activation initiates the
prothrombin time reaction
• The initial rise in the INR
may be due to rapid depletion
of FVII
• This does not correlate
with depletion of FX and FII
(prothrombin)
FX and prothrombin have long t½ and
take 4-5 days to be adequately
depleted – hence the need for 5 days
of overlap therapy
Parenteral Anticoagulant to
Warfarin Conversion
• In addition, to ensure consistency the INR
must be >2 on 2 consecutive days before
the parenteral agent is stopped.
• Therefore the MINIMUM time to achieve a
therapeutic INR is 5 days.
• Most patients will require approximately 7
days to complete anticoagulant conversion
to a stable INR on warfarin.
Anticoagulation Medication
Reconciliation
• New drop down box specific to
anticoagulant drugs
 Show screen shot of the drop down
• Will include a question about whether the
patient had a DVT or PE confirmed during
this hospital admission. If yes, then you
must enter in the date of the diagnostic
test that gave the confirmation
• May enter up to 2 anticoagulants that the
patient is being discharged on.
Anticoagulation Medication
Reconciliation
New drop down box specific to anticoagulant
drugs
• May enter up to 2 anticoagulants
prescribed at the time of discharge
Anticoagulation Medication
Reconciliation
• Will include a question about whether the
patient had a DVT or PE confirmed during
this hospital admission. If yes, then you
must enter in the date of the diagnostic
test that gave the confirmation.
Question
Date
Summary #3
• Overlap therapy for a MINIMUM of 5 days
and until a stable therapeutic INR > 2 on 2
consecutive days is required for patients
with VTE treated with AC.
• Med reconciliation and documentation is
imperative for success
Safe Discharge on
Anticoagulation
Why do we care about
Warfarin?
• It is the most commonly prescribed
anticoagulant
 >31
Million prescriptions dispensed in 2004
• It is the medication most commonly
responsible for serious & life-threatening
adverse reactions
therapeutic window  fine line
between being helpful & harmful
 Narrow
• Among the top 5 drugs contributing to ER visits
• Among the top 2 drugs causing hospitalization
Warfarin
Anticoagulant effect (VII, IX)
vs.
Antithrombotic effect (X, II)
Anticoagulant effect can be seen within 2 days
Antithrombotic effect takes minimum of 4-5 days due
to the t ½ of prothrombin (24-48 hours)
Dosing Variability
The average warfarin dose
is 5 mg.
Loading doses do not help
achieve a therapeutic INR
more quickly given the
need for a 5 day overlap
From Mol Interventions 6: 223-227
Warfarin
• Current ACCP guidelines recommend 5-10 mg initial
dosing

In the elderly, patients who are debilitated, malnourished, have
CHF, liver disease or recent surgery or who are taking
medications which increase sensitivity to warfarin - initial dose
should be ≤ 5 mg
• Hospital patients should RARELY receive more than 5
mg initial warfarin dosing
• “Loading doses” do not alter the need for overlap and
may increase the risk of bleeding
• Higher initial doses may be suitable for stable, healthy
outpatients
Chest 2008;133(3Suppl):454-545.
Warfarin Follow Up Appointment
All patients discharged on Warfarin:
• Discharge instructions must include an appointment for Warfarin
follow up monitoring.
• Discharging provider enters this information in the follow up section
on patient profile (CMC) which has a new option specific to Warfarin
follow up.
• Includes:
 The clinic or physician that will cover the follow up monitoring
• UH “Coumadin Clinic” is called “Anticoagulation Monitoring
Service”
 Phone number
 Date next PT/INR is due
Summary #4
• Choose warfarin initiation doses based on
patient characteristics
• NOT 5 mg for everyone
• Usually after hospital dc warfarin dose
requirements decrease
 ABX
 Diet
interruption
 Co-morbid/intervening illness
Anticoagulation Monitoring
Service
AKA – Coumadin Clinic
Anticoagulation Monitoring Service
Referral
AMS Referral
Anticoagulation Monitoring Service
Referral
Steps to schedule an initial visit to the Anticoagulation Monitoring Service:
1. An appointment must be scheduled for the patient to be seen; they are not "walk-in" visits.
2. Complete this form and fax to 216-844-1780 along with recent office note or discharge
summary.
(Concord Health Center only fax to (440)358-5481 and Geauga only fax to (440)285-6110).
3. Call 216-844-3800 to notify Anticoagulation Monitoring Service of patient and confirm receipt of
order form; this will ensure transition of patient and help to prevent gaps in care. An initial
appointment can be made for the patient at this time or the scheduling office will contact the
patient to schedule. Our goal is to see your patient within 3-5 business days.
4. Orders cannot be taken from Residents, Fellows, CNP's or PA's; a managing physician
MUST be listed.
5. The referring physician must ensure an interim management plan is in place until the patient
can be seen.
6. The referring physician must ensure that there is a managing physician responsible for the
ongoing needs of the patient. The managing physician will be contacted by the Anticoagulation
Monitoring Service staff for any patient care related issues.
7. Compliance with appointments and/or medication regimen is expected, otherwise patients will
be discharged from the anticoagulation monitoring service with ample warning.
Anticoagulation Monitoring Service
Responsibilities of the Anticoagulation Monitoring Service Staff:
1. If we are unable to schedule the visit within 3-5 business days of
receiving the form or being discharged from the hospital, you will be
contacted by our office.
2. The clinic staff cannot initiate anticoagulant therapy, nor can they bridge
therapy without orders from the managing physician. Furthermore, they will
not assume responsibility for the monitoring of the patient's anticoagulation
until the patient has been seen for the initial visit.
3. Progress notes will be sent to the managing physician's office via fax
after each visit.
Criteria for patient enrollment in the Anticoagulation Monitoring Service:
1. Patient is ambulatory and able to come to the clinic for appointments.
The clinic will not provide anticoagulation monitoring for patients receiving
home health, hospice or those getting venous punctures at a laboratory.
2. Patients without a managing physician will not be enrolled in the
Anticoagulation Monitoring Service.
3. Patients/caregiver should have no previous compliance issues
documented and is a willing, active participant in their care.
Therefore – engage the PCP
early and often
Begin the referral process early
Anticoagulation Management
• Must document and
“manage” all aspects of
anticoagulation
• Minimum of 5 days
overlap required
• INR max 3 days after
starting therapy
• Min every 2 days during
the transition
• Need 2 checks the week
following
Anticoagulation Monitoring Service
SUMMARY
• Monitor anticoagulation for a MANAGING PHYSICIAN

Nurse driven protocol following the orders of the physician
• We ARE NOT responsible for the patient until the first
visit – usually 3-5 days after dc


If the visit is delayed someone else needs to be monitoring
If the visit is missed someone else is responsible
• We do NOT dose adjust without orders
• Expectations are that the orders are followed – any
desirable adjustments may be made and will be followed

ie. shorter or longer intervals for management
• If warfarin or lovenox etc are required the managing
physician must be engaged

We will facilitate referrals for the physician with the pharmacy
Warfarin Follow Up Appointment
All patients discharged on Warfarin:
• Discharge instructions must include an appointment for Warfarin
follow up monitoring.
• Discharging provider enters this information in the follow up section
on patient profile (CMC) which has a new option specific to Warfarin
follow up.
• Includes:
 The clinic or physician that will cover the follow up monitoring
• UH “Coumadin Clinic” is called “Anticoagulation Monitoring
Service”
 Phone number
 Date next PT/INR is due
Referral Numbers
• Phone: 216-286-7010
• Fax: 216-201-6012
SUMMARY #5
• When anticoagulation is going to be
required engage the PCP early and often
• Begin the referral process early
Conclusions
• On admission ALL patients require DVT risk assessment
and prophylaxis orders
• Heparin when required - use the order sets

High dose vs. Low dose
• Anti-Xa monitoring is the UHCMC standard for adult
patients
• Overlap therapydocumented is required AND must be
• Discharge on anticoagulation requires effort

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PCP contact for follow up/monitoring
AMS referral
Interim plan for delays in presenting to the AMS
****LMWH or other anticoagulants may require pre-authorization
so request SW/pharmacy approvals early