Anticoagulation Issues at University Hospitals Case Medical Center AKA

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Anticoagulation Issues at University Hospitals
Case Medical CenterAKA ALMOST everything you
need to know for successful AC management

• Teresa L. Carman, MD
• Director, Vascular Medicine
• Case Medical Center
• Pager 33515
• Office 41261

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Discussion

• 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

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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

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IV Heparin Protocol

• Full Protocol Includes
• Initial Loading Bolus
• Titrated Drip know the drip rate
• Additional (Repeat) Bolus (as required)

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

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

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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
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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

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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.
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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.
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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.
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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 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

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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.
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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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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 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

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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

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Anticoagulation Core Quality Measures
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What are Core Measures ?

• Evidence based clinical measures that assess
  quality of care
• 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

University Hospitals Case Medical Center
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9/21/2013
Quality Assurance/Peer Review Report Privileged
Pursuant to O.R.C. Section 2305.24, .251, .252
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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/

9/21/2013
Quality Assurance/Peer Review Report Privileged
Pursuant to O.R.C. Section 2305.24, .251, .252
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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

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Anticoagulation Committee

• Approach
• Fit compliance into current clinician workflow
• No additional resources
• No retrospective chart abstraction

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Basic Essentials

• All patients require DVT prophylaxis screen on
  admission
• The proper prophylaxis is ordered or an
  appropriate reason for omission 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
• 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

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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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Summary 2

• All patients are risk stratified on admission
• All patients have prophylaxis ordered or a
  specific indication for not ordering prophylaxis
  is required.

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UFH, LMWH, Fondaparinux Overlap with Warfarin to
a Therapeutic INR

• Rational for a 5 Day Overlap and Discharging
  Patients on Warfarin

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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 gt 2 on 2 consecutive days before
  stopping the parenteral agent

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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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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

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Warfarin Effects

• Water soluble, readily absorbed from the GI tract
• Interferes with Vitamin K dependent
  ?-carboxylation
• Coagulant factors
• II, VII, IX, and X
• Anticoagulants
• protein C and S

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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

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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.

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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
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Parenteral Anticoagulant to Warfarin Conversion

• In addition, to ensure consistency the INR must
  be gt2 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.

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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.

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Anticoagulation Medication Reconciliation

• New drop down box specific to anticoagulant drugs
• May enter up to 2 anticoagulants prescribed at
  the time of discharge

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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
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Summary 3

• Overlap therapy for a MINIMUM of 5 days and until
  a stable therapeutic INR gt 2 on 2 consecutive
  days is required for patients with VTE treated
  with AC.
• Med reconciliation and documentation is
  imperative for success

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Safe Discharge on Anticoagulation
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Why do we care about Warfarin?

• It is the most commonly prescribed anticoagulant
• gt31 Million prescriptions dispensed in 2004
• It is the medication most commonly responsible
  for serious life-threatening adverse reactions
• Narrow therapeutic window ? fine line between
  being helpful harmful
• Among the top 5 drugs contributing to ER visits
• Among the top 2 drugs causing hospitalization

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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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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
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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
• 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 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 Clinic is called Anticoagulation
  Monitoring Service
• Phone number
• Date next PT/INR is due

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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

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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

• 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 [phone]
  and Geauga only fax to [phone]).
• 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.

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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.

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Therefore engage the PCP early and oftenBegin
the referral process early
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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 ServiceSUMMARY

• 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 Clinic is called Anticoagulation
  Monitoring Service
• Phone number
• Date next PT/INR is due

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Referral Numbers

• Phone [phone]
• Fax [phone]

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SUMMARY 5

• When anticoagulation is going to be required
  engage the PCP early and often
• Begin the referral process early

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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
• Overlap therapydocumented is required AND must be
• Discharge on anticoagulation requires effort
• 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