Anticoagulant Safety and National Patient Safety Goal 3E

1
Anticoagulant Safety and National Patient Safety
Goal 3E

• Reduce the Likelihood of Patient Harm Associated
  With the Use of Anticoagulant Therapy

2
Objectives

• Discuss National Patient Safety Goal 3E.
• Identify important information relating to
  Heparin usage.
• Recognize important information relating to LMWH
  and fondaparinux usage.
• Describe important aspects of warfarin usage.
• Discuss the role of patient/family education
  relating to NPSG 3E.
• Identify key actions relating to deep vein
  thrombosis prevention.

3
Authors/Editors

• The content of the course was provided by Carl
  Peterson, Pharm. D. He has been affiliated with
  Cardinal Health since 1995 and is currently
  Clinical Director of Cardiovascular Diseases for
  the Center for Safety and Clinical
  Excellence. Dr. Peterson has also served as a
  consultant on advisory panels for
  Sanofi-AventisTM, which is the manufacturer of
  Lovenox. Dr. Peterson does not have any actual
  conflicts of interest in relation to this
  program.
• The course was edited by Curt W. Quap, M.S.,
  R.Ph, Director of Clinical Affairs and Angela
  Gomez, Ph.D., Manager of Clinical Education and
  Training.

4
Outline

• NPSG 3E
• Heparin essentials
• LMWH and fondaparinux essentials
• Warfarin essentials
• Patient/family education
• DVT prevention

5
Improving Anticoagulant Safety

• National Patient Safety Goals
• Purposepromote specific improvements in patient
  safety.
• Goals, requirements, implementation expectations
  recommended to Joint Commission Board by expert
  Advisory Group.
• Compliance assessed via on-site surveys and
  Periodic Performance Review.
• Failure to comply can lead to loss of
  accreditation

6
Improving Anticoagulant Safety

• National Patient Safety Goal 3E
• Reduce the likelihood of patient harm associated
  with the use of anticoagulation therapy
• Anticoagulation is a high risk treatment, which
  commonly leads to adverse drug events due to the
  complexity of dosing these medications,
  monitoring their effects, and ensuring patient
  compliance with outpatient therapy.
• The use of standardized practices that include
  patient involvement can reduce the risk of
  adverse drug events associated with the use of
  heparin (unfractionated), low molecular weight
  heparin (LMWH), warfarin, and other
  anticoagulants.

7
NPSG 3E Implementation Timeline

• 4/1/08 Organization leadership assigns
  responsibility for oversight and coordination of
• Development
• Testing
• Implementation
• 7/1/08 Implementation work plan in place that
  identifies
• Adequate resources
• Assigned accountabilities
• Time line for full implementation
• 10/1/08 Pilot testing in at least one clinical
  unit is underway
• 1/1/09 Process fully implemented across the
  organization

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NPSG 3E Implementation Expectations

• A 1. The organization implements a defined
  anticoagulant management program to individualize
  the care provided to each patient receiving
  anticoagulant therapy.
• A 2. To reduce compounding and labeling errors,
  the organization uses ONLY oral unit dose
  products and pre-mixed infusions, when these
  products are available.
• C 3. When pharmacy services are provided by the
  organization, warfarin is dispensed to each
  patient in accordance with established monitoring
  procedures.

9
NPSG 3E Implementation Expectations

• C 4. The organization uses approved protocols
  for the initiation and maintenance of
  anticoagulation therapy appropriate to the
  medication used, to the condition being treated,
  and to the potential for drug interactions.
• C 5. For patients being started on warfarin, a
  baseline International Normalized Ratio (INR) is
  available, and for all patients receiving
  warfarin therapy, a current INR is available and
  is used to monitor and adjust therapy.
• C 6. When dietary services are provided by the
  organization, the service is notified of all
  patients receiving warfarin and responds
  according to its established food/drug
  interaction program.

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NPSG 3E Implementation Expectations

• A 7. When heparin is administered intravenously
  and continuously, the organization uses
  programmable infusion pumps.
• C 8. The organization has a policy that
  addresses baseline and ongoing laboratory tests
  that are required for heparin and low molecular
  weight heparin therapies.
• C 9. The organization provides education
  regarding anticoagulation therapy to staff,
  patients, and families.

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NPSG 3E Implementation Expectations

• C 10. Patient/family education includes the
  importance of follow-up monitoring, compliance
  issues, dietary restrictions, and potential for
  adverse drug reactions and interactions.
• A11. The organization evaluates anticoagulation
  safety practices.

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Outline

• NPSG 3E
• Heparin essentials
• LMWH and fondaparinux essentials
• Warfarin essentials
• Patient/family education
• DVT prevention

13
Sites of Action
12
12a
tissue thromboplastin
11
11a
7
7a
9a
9
10a
10
10
thrombin
prothrombin
fibrinogen
fibrin
heparin
14
Heparin aPTT Therapeutic Range
aPTT Variation by Reagent Manufacturer
Solid 1.5-2.5 x control Hatched 0.2-0.4 u/ml
Brill-Edwards et al. Ann Int Med 1993119104-9.
15
Example Heparin Curve
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Starting Heparin

• Patient information
• Indication for treatment
• Goals of therapy
• Target aPTT
• Bleeding risk
• Baseline lab values
• aPTT or anti-10a activity
• CBC, platelets
• Basic chemistries

IE 8-- policy addresses baseline and ongoing
lab tests
17
Weight-Based Heparin Dosing
IE 4-- organization uses approved protocols
18
Monitoring Heparin

• aPTT
• Q6 hrs until stable therapeutic aPTT
• aPTT at least daily
• Resume 6 hourly monitoring after dose adjustments
• Platelet count
• Treatmentat least every other day
• Prophylaxisevery 2-3 days
• Continue until at least day 14
• CBC every 2-4 days as indicated
• Serum chemistry as indicated
• Hyperkalemia infrequently in diabetics
• Signs and symptoms of thromboembolic events
• Signs and symptoms of bleeding

IE 8-- policy addresses baseline and ongoing
lab tests
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Heparin-Induced Thrombocytopenia

• Immune response
• Heparin-dependent anti-platelet factor 4
  antibodies
• React with PF4/heparin complex
• Induce platelet aggregation
• Incidence and onset
• Varies with disease and dose, approx. 1-5
• Very rare lt5 days onset
• Rare delayed onset (gt 2 weeks)
• LMWH
• Less likely to form antibodies
• Lower incidence of clinical HIT
• Significant cross reactivity with formed
  antibodies

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Heparin-Induced Thrombocytopenia

• Clinical suspicion
• Sudden heparin resistance
• Disease recurrence in the presence of adequate
  anticoagulation
• Timing gt 5-7 days into therapy
• Laboratory suspicion
• Platelet count decrease to lt 150,000/mm3
• Decrease gt 50 from baseline regardless of
  absolute count
• Laboratory confirmation (should not delay
  treatment)
• HIT is a thrombotic disorder
• Venous and/or arterial thromboembolism
• Not associated with bleeding despite low platelet
  counts

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HIT Management

• Discontinue ALL heparin
• Is stopping heparin enough?

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HIT Management

• Discontinue ALL heparin
• Treatment options
• Direct thrombin inhibitor
• Lepirudinfirst line
• Argatrobanfirst line
• Bivalirudinsecond line (first line in cardiac
  cath lab)
• Discontinue warfarin, start or resume
• With platelet count recovery
• Full overlap with parenteral agent
• LMWH contraindicated
• Fondaparinux--no data

23
Outline

• NPSG 3E
• Heparin essentials
• LMWH and fondaparinux essentials
• Warfarin essentials
• Patient/family education
• DVT prevention

24
Sites of Action
12
12a
tissue thromboplastin
11
11a
7
7a
LMWH
9a
9
10a
10
10
prothrombin
thrombin
fibrinogen
fibrin
25
LMWH/Fondaparinux Monitoring

• Same baseline labs
• SCr important for dosing
• Same regular testing/clinical monitoring except
• No routine anticoagulation testing
• Examine for significant injection site hematoma
• Platelet counts
• LMWH--every 2-3 days
• Fondaparinuxspecific need or frequency not
  established

IE 8-- policy addresses baseline and ongoing
lab tests
26
Enoxaparin/Fondaparinux Dosing

• Enoxaparin
• Treatment--1 mg/kg Q12h (DVT only 1.5 mg/kg QD)
• ClCr lt 30 ml/min 1 mg/kg daily
• DVT prevention--40 mg daily or 30 mg BID
• ClCr lt 30 ml/min 30 mg daily
• Fondaparinux
• Treatment
• DVT/PE 5 mg, 7.5 mg or 10 mg daily by body weight
• ACS 2.5 mg daily (unapproved use)
• DVT prevention2.5 mg daily
• Not recommended for ClCr lt 30 ml/min

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LMWH Anti-10a Activity Monitoring

• Special populations (e.g., renal dysfunction with
  ClCr lt 30 ml/min, extreme obesity, pregnancy)
• When
• 2nd or 3rd dose
• Peak level 4 hours post SC dose
• If indicated, at the time of a clinical event
• Target range
• Every 12h dosing 0.6-1.0 Units/ml
• Every day dosing 1.0-2.0 Units/ml
• Dose adjustment
• Rough proportion
• Fondaparinux monitoringno data, not recommended

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Outline

• NPSG 3E
• Heparin essentials
• LMWH and fondaparinux essentials
• Warfarin essentials
• Patient/family education
• DVT prevention

29
Sites of Action
12
12a
tissue thromboplastin
11
11a
7
7a
t 1/2 6 hrs
9a
9
10a
10
10
t 1/2 40-60 hrs
prothrombin
thrombin
t 1/2 60-96 hrs
fibrinogen
fibrin
Protein C t 1/2 6 hrs
warfarin
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Starting warfarin

• Patient information
• Indication for treatment
• Goals of therapy
• Target INR
• Concurrent drugs
• Bleeding risk
• Baseline lab values
• INR
• CBC, platelets
• Basic chemistries

IE 5-- baseline INR Is available
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Typical Warfarin Dosing Nomogram
Crowther M et al. Ann Int Med 1997127333.
IE 4-- organization uses approved protocols
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Transitioning to Warfarin

• aPTT may increase as warfarin kicks in
• Do not discontinue parenteral agent until
• Minimum 4-5 day overlap regardless of INR
  response
• Two consecutive therapeutic INRs
• No strong direction of INR change

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Secrets to Warfarin Success

• Start early
• Avoid starting doses gt 5 mg unless dose
  requirement is already known
• lt 4 mg for elderly, frail, liver disease
• PM drug, AM INR
• Maximum single dose INR effect approx. 36 hrs
• INR is algebraic sum of 2-3 previous doses
• Patience is a virtuebig dose changes big
  problems
• Dose requirement often changes after discharge

34
Warfarin Drug/Drug and Food/Drug Interactions

• Drug/Drug
• Metabolism
• ? Enzyme induction
• ? Enzyme competition
• Protein binding
• ? Displacement
• Absorption
• ? Short gut
• Vitamin K
• ? Broad spectrum antibiotics

• Food/Drug
• Drug-like interactions
• Herbal remedies
• Increased vitamin K intake
• Rapid ?
• Decreased vitamin K intake
• Delayed ?

Arrows indicate direction of INR change
IE 6-- established food/drug Interaction program
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Outline

• NPSG 3E
• Heparin essentials
• LMWH and fondaparinux essentials
• Warfarin essentials
• Patient/family education
• DVT prevention

36
Warfarin Patient Education

• Why you are taking warfarin
• How warfarin works and how it will benefit you
• How and when to take warfarin
• Monitoring, dose-adjusting, and the INR
• Your role in your therapy including medication
  and blood testing compliance
• Communicating with all health care providers
• Diet
• Lifestyle considerations
• Potential for drug interactions including OTC and
  herbal products
• Address aspirin
• Signs and symptoms of thromboembolism and what to
  do
• Signs and symptoms of bleeding and what to do

IE 9, 10-- organization provides education to
staff, patients, families
37
LMWH/Fondaparinux Patient Education

• Why you are taking this drug
• How the drug works and how it will benefit you
• How and when to administer doses including
  aseptic technique
• Storage
• Monitoring
• Your role in your therapy including medication
  and blood testing compliance
• Communicating with all health care providers
• Lifestyle considerations
• Signs and symptoms of thromboembolism and what to
  do
• Signs and symptoms of bleeding and what to do

IE 9, 10-- organization provides education to
staff, patients, families
38
Outline

• NPSG 3E
• Heparin essentials
• LMWH and fondaparinux essentials
• Warfarin essentials
• Patient/family education
• DVT prevention

39
DVT Incidence by Surgery
DVT Incidence Without Prophylaxis
Chest 2001119 Suppl 1132S-75S
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DVT Incidence in Medical Patients

• Incidence by condition
• Ischemic stroke with paralysis 55
• MI 24
• General 16
• Mostly CHF, COPD, infectious diseases
• Proximal/symptomatic DVT approx. 5
• Why so little information?
• Wide range of medical conditions
• Wide variation in level of sickness
• Few trials compared to surgery

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DVT Risk Factors

• Other risk factors
• Obesity
• Pregnancy
• Estrogen use
• Venous insufficiency
• General immobility
• Nephrotic syndrome
• Indwelling venous catheter
• Medical conditions--e.g., CHF, respiratory,
  inflammatory bowel disease, pneumonia
• Cancer

• Major Risk Factors
• Age gt40 gt 60
• Surgery--minor vs major
• Anesthesia--type, duration
• Prior VTE
• Hypercoagulable state, inherited or acquired
• Hip/knee arthroplasty
• Hip fracture
• Major trauma
• Spinal cord injury
• Stroke with paralysis
• Cancer

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Selecting a DVT Prevention Regimen
Lowest DVT Risk Highest
lt 40
40-60
gt 60
Age
Minor
Nonmajor
Major
Surgery
Risk Factors
some
none
many
Heparin Q12 LMWH ES or IPC
Aggressive ambulation
Heparin Q8 LMWH IPC
LMWH Fondaparinux Warfarin
1st Line Tx
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DVT Risk Factor Assessment
44
Selecting a DVT Prevention Regimen
45
QA