1. Director, Vascular Medicine
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

2. 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

3. Heparin Order Set

4. 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 Initial Loading Bolus
Full Protocol Includes:
Initial Loading Bolus
Titrated Drip – know the drip rate
Additional (Repeat) Bolus (as required)

6. 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:
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

10. 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

11. aPTT VS. Heparin Assay Monitoring

12. 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 times aPTT control reduced risk the of recurrent thromboembolism
Eikelboom JW. Thromb Haemost 2006;96:
Francis JL. Pharmacotherapy 2004;24:108S-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 2006;96:
Francis JL. Pharmacotherapy 2004;24:108S-19S.

14. 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:
Francis JL. Pharmacotherapy 2004;24:108S-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 2008;133:141-59

16. Monitoring

17. 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

18. 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 2006;96:
Francis JL. Pharmacotherapy 2004;24:108S-19S.

19. 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
P<0.0001
P<0.0001
Rosborough TK. Pharmacotherapy 1999;19:

20. Current “High-Intensity Therapeutic Heparin” Anticoagulation Orders Using Heparin Assay for Adult Patients (VTE etc)

21. Current “Low-Intensity Therapeutic Heparin” Anticoagulation Orders Using Heparin Assay for Adult Patients (ACS, stroke)

22. 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

23. 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 = IU/ml
“low-dose” anti-Xa = IU/ml
The time between adjustments and monitoring will decrease to 4 hours in an effort to shorten the time to therapeutic

24. Anticoagulation Core Quality Measures

25. 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
A and C
4/13/2017
University Hospitals Case Medical Center
Quality Assurance/Peer Review Report Privileged Pursuant to O.R.C. Section , .251, .252 25 25

26. Where is Data Publicly Reported?
Hospital Compare
The Joint Commission
Ohio Department of Health
Leapfrog
Health Grades
A and C
4/13/2017
Quality Assurance/Peer Review Report Privileged Pursuant to O.R.C. Section , .251, .252 26

27. 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

28. Anticoagulation Committee
Approach
Fit compliance into current clinician workflow
No additional resources
No retrospective chart abstraction
Susan

29. 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

30. 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

31. Deep Vein Thrombosis Risk Screening
Carman

32. Deep Vein Thrombosis Risk Screening
Carman

33. Deep Vein Thrombosis Risk Screening
Carman - 2 mandatory parts of the screening

34. Deep Vein Thrombosis Risk Screening
Carman

35. Deep Vein Thrombosis Risk Screening
Carman

36. Deep Vein Thrombosis Risk Screening
Carman

37. Summary #2 All patients are risk stratified on admission
All patients have prophylaxis ordered – or – a specific indication for not ordering prophylaxis is required.

38. UFH, LMWH, Fondaparinux Overlap with Warfarin to a Therapeutic INR
Rational for a 5 Day Overlap and Discharging Patients on Warfarin

39. 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

40. 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)

41. 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

42. Warfarin Effects Water soluble, readily absorbed from the GI tract
Interferes with Vitamin K dependent γ-carboxylation
Coagulant factors
II, VII, IX, and X
Anticoagulants
protein C and S

43. 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

44. 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.

45. 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

46. 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.

47. 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.

48. Anticoagulation Medication Reconciliation
New drop down box specific to anticoagulant drugs
May enter up to 2 anticoagulants prescribed at the time of discharge

49. 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

50. 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

51. Safe Discharge on Anticoagulation

52. 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
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

53. 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)

54. 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:

55. 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):

56. 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

57. 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

58. Anticoagulation Monitoring Service AKA – Coumadin Clinic

59. Anticoagulation Monitoring Service Referral

60. AMS Referral

61. 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 along with recent office note or discharge summary.
(Concord Health Center only fax to (440) and Geauga only fax to (440) ).
3. Call 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.

62. 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.

63. Therefore – engage the PCP early and often Begin the referral process early

64. 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

65. 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

66. 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

67. Referral Numbers
Phone:
Fax:

68. SUMMARY #5
When anticoagulation is going to be required engage the PCP early and often
Begin the referral process early

69. 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