Unique Anticoagulation Issues at University Hospitals Case Medical Center

1
Unique Anticoagulation Issues at University
Hospitals Case Medical Center

• Teresa L. Carman, MD
• Director, Vascular Medicine
• Case Medical Center
• Pager 33515

2
Discussion

• Use of the heparin protocol
• Anti-Xa assay vs. aPTT
• Safe discharge of patients
• Anticoagulation monitoring service referrals

3
Heparin Order Set
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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

5
IV Heparin Protocol

• Full Protocol Includes
• Initial Loading Bolus
• Titrated Drip
• Additional (Repeat) Bolus

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IV Heparin Protocol Ordering
Choose the Loading Dose to order the initial
bolus
7
IV Heparin Protocol Ordering

• Choose Continuous Infusion to order the drip
• Includes standard nurse driven titration protocol

8
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
9
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

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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

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aPTT VS. Heparin Assay Monitoring
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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 1.5-2.5 times aPTT control reduced risk
  the of recurrent thromboembolism

Eikelboom JW. Thromb Haemost 200696547-52. Franc
is JL. Pharmacotherapy 200424108S-19S.
13
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 200696547-52. Franc
is JL. Pharmacotherapy 200424108S-19S.
14
Conditions that May Prolong the Baseline aPTT

• Lupus anticoagulants
• Other antiphospholipid antibodies
• Prekallikrein, High Molecular Weight Kininogen
  Level
• Low levels (lt40) of
• Fibrinogen
• Prothrombin
• Factors V, VIII, IX, X, XI, and XII

Eikelboom JW. Thromb Haemost 200696547-52. Franc
is JL. Pharmacotherapy 200424108S-19S.
15
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 2008133141-59
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Monitoring
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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

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Heparin Assay

• Specifically determines anticoagulant activity of
  IV unfractionated heparin by measuring ability of
  heparin-bound 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 200696547-52. Franc
is JL. Pharmacotherapy 200424108S-19S.
19
Limitations of Heparin Assay

• Clinical data examining outcomes is limited

Eikelboom JW. Thromb Haemost 200696547-52. Franc
is JL. Pharmacotherapy 200424108S-19S.
20
Comparison of Monitoring with aPTT vs.
Anti-Factor Xa Assay

• Prospective, single-center study
• 268 patients on IV heparin for variety of
  indications
• Utilizing anti-Factor Xa assay led to fewer tests
  and dose adjustments
• Cost increase of 1.09/day more using anti-Factor
  Xa assay

Plt0.0001
Plt0.0001
Rosborough TK. Pharmacotherapy 199919760-66.
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High-Intensity Therapeutic Heparin
Anticoagulation Orders for Adult Patients
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Current High-Intensity Therapeutic Heparin
Anticoagulation Orders Using Heparin Assay for
Adult Patients (VTE etc)
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Current Low-Intensity Therapeutic Heparin
Anticoagulation Orders Using Heparin Assay for
Adult Patients (ACS, stroke)
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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

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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.
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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

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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.

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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)

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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

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Essentials

• All patients require DVT prophylaxis screen on
  admission
• The proper prophylaxis is ordered or an
  appropriate reason of ommission is documented
• Hospital acquired VTE is considered a never
  event
• VTE treatment transition must meet current
  guidelines and this is documented and supported
  by the discharge orders

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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

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Deep Vein Thrombosis Risk Screening
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Deep Vein Thrombosis Risk Screening
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Deep Vein Thrombosis Risk Screening
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Deep Vein Thrombosis Risk Screening
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Deep Vein Thrombosis Risk Screening
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Deep Vein Thrombosis Risk Screening
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Safe Discharge on Anticoagulation
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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.

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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)

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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 2008133(3Suppl)454-545.
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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

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Anticoagulation Monitoring ServiceAKA Coumadin
Clinic
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Anticoagulation Monitoring Service Referral
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AMS Referral
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Anticoagulation Monitoring Service Referral
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Anticoagulation Monitoring Service
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Therefore engage the PCP early and often
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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

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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

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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

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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
  pre-authorization so request SW/pharmacy
  approvals early