Unique Anticoagulation Issues at
University Hospitals Case
Medical Center
Teresa L. Carman, MD
Director, Vascular Medicine
Case Medical Center
Pager 33515
Discussion
•
•
•
•
Use of the heparin protocol
Anti-Xa assay vs. aPTT
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
Additional
(Repeat) Bolus
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:
• Full protocol 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 use of the “aPTT, heparin”
is not available for monitoring IV unfractionated
heparin therapy at University Hospitals Case
Medical Center. (no correlations have been done)
• The “aPTT, heparin” 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.
Limitations of Heparin
Assay
• Clinical data examining outcomes is
limited
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.
“High-Intensity Therapeutic Heparin”
Anticoagulation Orders for Adult Patients
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 be used to
monitor warfarin
• Therapeutic monitoring of direct thrombin
inhibitors (bivaliruding and argatroban)
still use the aPTT
• Special monitoring for enoxaparin
(Lovenox®) is done by Heparin assay,
Lovenox
Summary Order Set
Changes
Heparin assay, UFH will be done after initiation and dose changes as well as
each morning. Timing will be changed to a 4 hour response time for all dose
adjustments.
Summary
• 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
Summary
• No changes will occur related to warfarin
monitoring
Prothrombin
time/INR is the
standard
• No changes will occur related to direct
thrombin inhibitor monitoring, aPTT
• Enoxaparin (Lovenox®) is monitored by
the Heparin assay, Lovenox.
Overview of the Trends In VTE
Management
• Prevention** - to decrease the incidence of VTE

ALL PATIENTS REQUIRE PROPHYLAXIS**
• Improved sensitivity/specificity and ease of
diagnosis
• Improve treatment – increased efficacy and
reliability of pharmaceuticals
• Improve outcomes - decrease risk of recurrence
• Decrease longterm morbidity from VTE


Post-thrombotic syndrome (PTS)
Chronic thromboembolic disease (CTED)
Anticoagulation Committee
• Meaningful Use VTE quality measure
– VTE prophylaxis within 24 hours of arrival
– ICU VTE
– Anticoagulation overlap therapy
– Platelet monitoring for unfractionated heparin
– Comprehensive discharge instructions
– Incidence of potentially preventable VTE
• Approach
– Fit compliance into current clinician workflow
• No additional resources
• No retrospective chart abstraction
Essentials
1. All patients require DVT prophylaxis screen on
admission
2. The proper prophylaxis is ordered or an
appropriate reason of ommission 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
– Includes orders based on risk score for both
pharmacologic and mechanical
– 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
Safe Discharge on
Anticoagulation
Anticoagulation Medication
Reconciliation
• New drop down box specific to
anticoagulant drugs
 Show screen shot of the drop down
• May enter up to 2 anticoagulants that the
patient is being discharged on
• 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.
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)
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
• Hospitals patients should RARELY receive more than 5
mg initial coumadin dosing
• Higher initial doses may be suitable for stable, healthy
outpatients
• Monitoring should begin after 2-3 doses
• 5 mg vs. 10 mg initial dose debate


Early INR changes are due to FVII depletion
Minimum of 4-5 days are required to deplete FX and FII
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 Clinics” are now called “Anticoagulation
Monitoring Services”
 Phone number
 Date next PT/INR is due
Anticoagulation Monitoring
Service
AKA – Coumadin Clinic
Anticoagulation Monitoring Service
Referral
AMS
Referral
Anticoagulation Monitoring Service
Referral
Anticoagulation Monitoring Service
Therefore – engage the PCP
early and often
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
• 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 Clinics” are now called “Anticoagulation
Monitoring Services”
 Phone number
 Date next PT/INR is due
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
• Discharge on anticoagulation requires effort




PCP contact for follow up
AMS referral
Interim plan for delays in presentation to the AMS
****LMWH or other anticoagulants may require preauthorization so request SW/pharmacy approvals
early