D22 CAVHS ANTICOAGULATION THERAPHY MANAGEMENT POLICY.pdf

DEPARTMENT OF VETERANS AFFAIRS MEMORANDUM NO. 11-36

Central Arkansas Veterans Healthcare February 12, 2018 Little Rock/North Little Rock

ANTICOAGULATION THERAPY MANAGEMENT

1. PURPOSE: To establish policy and procedure for the proper management of patients receiving therapeutic anticoagulation therapy and to establish the Anticoagulation Therapy Management Program (ATMP) at Central Arkansas Veterans Healthcare System (CAVHS).

2. POLICY:

a. Definitions:

(1) Ancillary testing is defined as laboratory testing or services performed within a Veterans Administration (VA) Medical Center or its outreach functions (clinic, et al.), but outside the physical facilities of the main clinical laboratory. Specific to anticoagulation, ancillary testing is often done for the prothrombin time/ international normalized ratio (PT/INR) and referred to as point of care testing (POCT).

(2) Anticoagulant is the term for a medication that inhibits blood coagulation and may include warfarin, direct oral anticoagulants (DOACs), unfractionated heparin, (UFH), low molecular weight heparin (LMWH), direct thrombin inhibitor (DTI), or anti-Xa inhibitors.

(3) Bridge therapy is the temporary use of a short and immediate acting injectable anticoagulant during time periods when warfarin or DOACs are intentionally held or when the INR level falls below the therapeutic level.

(4) Therapeutic anticoagulation includes active therapy and long-term prophylaxis where the clinical expectation is for the patient's laboratory value to remain outside normal values. It does not include the use of short-term prophylactic anticoagulation for prevention of thromboembolism where the patient's laboratory value is expected to remain within or close to normal values nor does it include the use of anticoagulants for catheter line maintenance.

b. Patients receiving anticoagulation therapy from this facility will be managed and/or followed through the ATMP. This will include anticoagulation for both inpatients and outpatients treated at the Little Rock and North Little Rock campuses as well as the Community Based Outpatient Clinics (CBOC).

c. The anticoagulation management program will be organized under the direction of the Anticoagulation Therapy Program Director (ATPD).

d. The ATMP will individualize therapy for each patient utilizing established dosing and monitoring protocols.

e. Anticoagulants covered by the policy include UFH, LMWH, anti-Xa inhibitors, DTI, DOACs, and warfarin. This policy does not cover use of anticoagulants for nontherapeutic purposes such as short-term prevention or catheter line maintenance.

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MEMORANDUM NO. 11-36

f. Patients who choose to have their anticoagulant therapy managed by a provider outside the facility or participate in a self-testing program must purchase the medication, monitor and supplies at their own expense. This includes warfarin, direct oral anticoagulants, as well as injectable anticoagulants. This practice is to ensure patient safety regarding these high risk medications by prohibiting co-management and/or self-testing.

g. Patients receiving care from other VA anticoagulation management programs that travel to this area on a temporary basis may have courtesy laboratory monitoring completed at this facility under the direction of the ATMP. The patient will be notified of test results and will be instructed to contact his home facility for instructions for consistency in anticoagulation management. In the event of a critical laboratory result, the ATMP will follow up with the patient to assure appropriate action has been taken.

h. The quality of anticoagulation provided will be monitored consistently throughout the facility in acute care, long term care and ambulatory care settings.

3. RESPONSIBILITIES:

a. Clinical Executives (Chief of Staff and Chief Nurse Executive) are responsible for ensuring:

(1) Programmable infusion pumps are used for the intravenous administration of heparin and DTI therapy.

(2) Mid-level medical and nursing staff involved in managing anticoagulation has successfully completed a specialty training program or is certified as an anticoagulation care provider or complete an on-site anticoagulation training program that includes both a didactic and experiential component.

(3) Anticoagulation education will be provided to providers and staff caring for patients on anticoagulation therapy as needed based on quality assurance and performance improvement activities.

(4) The competency plan for mid-level medical and nursing staff practitioners involved in managing anticoagulation therapy will include a critical element specific for anticoagulation to include ancillary testing if applicable.

b. Chief, Pharmacy Service is responsible for ensuring:

(1) Only oral unit dose products, pre-filled syringes and pre-mixed infusion bags are used for anticoagulant medications in the inpatient setting.

(2) The number of concentrations and quantities of heparin vials stocked in patient and procedural areas is limited to the minimum to meet patient care needs.

(3) When anticoagulants are stored in automated dispensing devices, especially when multiple strengths or concentrations of the same anticoagulant are available, they are clearly labeled as high alert medications and are stored in separate drawers.

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(4) Pharmacy staff involved in managing anticoagulation has successfully completed a specialty training program, is certified as an anticoagulation care provider or completed an on-site anticoagulation training program that includes both a didactic and experiential component.

(5) Anticoagulation education will be provided to providers and staff caring for patients on anticoagulation therapy as needed on quality assurance and performance improvement activities.

(6) The competency plan for mid-level pharmacy staff involved in managing anticoagulation therapy will include a critical element specific for anticoagulation to include ancillary testing if applicable.

c. Chief, Nutrition and Food Service is responsible for ensuring:

(1) Inpatients receiving warfarin have appropriate meal planning to assure a consistent dietary intake of vitamin K.

(2) Patients on warfarin receive education regarding food/medication interaction.

d. Chief, Pathology and Laboratory Medicine Service is responsible for ensuring:

(1) Critical laboratory values are communicated from the laboratory to the provider within 60 minutes of receipt of the specimen in the laboratory per MCM No. 00S-23, Reporting Critical Diagnostic Test Results.

(2) Education and training of staff involved in POCT and assessing the competency of staff involved in ancillary testing.

(3) Assuring that a standardized process is adhered to when documenting laboratory values performed at CBOC facilities. These laboratory values may be entered into the Veterans Health Information Systems and Technology Architecture (VISTA) laboratory package with appropriate verification.

(4) Evaluating the turnaround time of INR results for outpatients on warfarin therapy.

e. Anticoagulation Therapy Program Director is responsible for ensuring:

(1) Communication between the ATMP staff as well as coordination of the day to day operations of the program.

(2) Ongoing monitoring of the facility anticoagulant quality assurance plan and reporting of results to the Quality Management Committee for approval.

(3) Education regarding anticoagulation is provided to patients and families.

(4) Annual education regarding anticoagulation is provided to all staff involved in patient care.

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4. PROCEDURE:

a. Anticoagulation therapy will be initiated in the Computerized Patient Medical Record (CPRS) by the provider using approved, evidence based protocols.

Warfarin:

(1) Initiation of therapy will be accomplished through use of the Coumadin Clinic Consult in CPRS. This includes the measurement of a baseline PT/INR. Initiation of direct oral anticoagulants will be accomplished through use of a drug specific consult, which will include the measurement of baseline INR, liver function tests, CBC, and serum creatinine.

(2) Maintenance of therapy will be based on Guidelines for Warfarin Maintenance (Attachment A) with adjustments made based on clinical judgment of the provider and individual patient characteristics.

(3) Elevations in the INR or bleeding will be managed based on current American College of Chest Physician (ACCP) guidelines (Attachment B) with adjustments made based on clinical judgment of the provider and individual patient characteristics.

(4) Warfarin and direct oral anticoagulant therapy will be managed by the ATMP surrounding invasive procedures via a consult service. Patients will be evaluated for the risk of thrombosis versus bleeding. Risk stratification will be performed to determine if the bridging protocol should be implemented (Attachment C).

(5) The bridging protocol may be implemented when warfarin or direct oral anticoagulant doses are to be intentionally held, when warfarin therapy is initiated or the INR is subtherapeutic (Attachment C).

(6) UFH will be initiated and managed using the weight-based heparin order set (Attachment F).

(7) LMWH therapy will be initiated in CPRS through use of the enoxaparin order set.

(8) Injectable Anti-Xa inhibitors will be initiated in CPRS through use of the fondaparinux order set.

(9) Patients with the diagnosis of heparin induced thrombocytopenia (HIT) will be managed using the HIT Protocol (Attachment G) using injectable DTI therapy.

b. Laboratory monitoring for anticoagulation will include:

(1) UFH

(a) Baseline: Complete Blood Count (CBC) with platelets; activated partial thromboplastin time (aPTT).

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(b) Ongoing: aPTT in 6 hours then at 6 or 12 hours per protocol; CBC with platelets every other day.

(2) LMWH and injectable anti-Xa inhibitors:

(a) Baseline: CBC with platelets; serum creatinine.

(b) Ongoing: CBC with platelets; serum creatinine if a change in patient status is suspected.

(3) Warfarin:

(a) Baseline: CBC with platelets; PT/INR (note that initial PT/INR should not be performed using POCT).

(b) Ongoing: CBC with platelets; A current PT/INR must be available to allow warfarin management. All patients initiated on warfarin must have an INR measurement within 7 days of initiation. In acute care settings, the INR is to be done at least every 3 days. In long term care settings, the INR is to be done at least every 4 weeks. If the INR is greater than or equal to 4 or if no INR has been done within the defined timeframe, the warfarin dose is to be held until the provider can be contacted for instruction. In the outpatient setting, the INR should be checked at no more than 4 week intervals in stable patients. To allow for situations where stable patients are unable to have their INR checked in 4 weeks, a maximum of 6 week intervals may be used at the clinical judgment of the provider.

(4) Direct Oral Anticoagulants:

(a) Baseline: Serum Creatinine (SCr); complete blood count (CBC) with platelets, liver function tests (LFTs), and INR.

(b) Outpatient and Long Term Care Setting Follow-up monitoring; 2 week phone follow then Serum Creatinine (SCr); complete blood count (CBC) with platelets, LFTs, and INR at 3 months or as needed. After the initial 3 month period, the patients will be followed by his/her Primary Care Provider.

(c) Inpatient Follow-up monitoring; Serum Creatinine (SCr) should be monitored at least weekly as changes in renal function may necessitate a change in dose. Changes in complete blood count (CBC) with platelets and LFTs should be monitored periodically for toxicities.

(5) Injectable DTI:

(a) Baseline: CBC with platelets; aPTT; liver function tests (argatroban); PT/INR (argatroban); serum creatinine (lepirudin and bivalirudin).

(b) Ongoing: aPTT in 2 to 4 hours per protocol or activated clotting time (ACT) in 5 to 10 minutes then per protocol based on indication for use; serum creatinine if a change in patient status is suspected (note that argatroban elevates the INR therefore special caution is needed when patients are converted over to warfarin).

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c. In the inpatient setting:

(1) The clinical pharmacist will monitor the anticoagulation therapy and make recommendations to the patient care team. The pharmacist may order testing and adjust medication doses in accordance with their Scope of Practice and the preference of the patient care team.

(2) Patients and their caregivers will be provided education that includes the importance of follow up monitoring, compliance, dietary restrictions and the potential for adverse drug reactions and interactions. In addition, they will be educated regarding oral anticoagulants including tablet identification, indication for therapy, drug, diet and disease interactions, daily dosage, monitoring requirements, the importance of medication adherence, the dangers of using oral anticoagulants from different sources, the management of missed doses, the signs and symptoms of bleeding and thromboembolic events and the risks associated with falling. Patients and their caregivers may also be provided education regarding injection technique if appropriate.

Documentation of education will be made in CPRS using approved progress note templates or clinical reminders.

(3) The clinical pharmacist is responsible for hand off communication regarding anticoagulation to the next provider of care when the patient is transferred within or discharged from the facility.

(4) The clinical dietitian will be notified of all patients receiving warfarin and meal services, then will respond per established food and medication interaction protocols designed to promote steady vitamin K intake. Meal plans and patient dietary education will be individualized to meet overall health needs supporting an adequate dietary Reference Intake for vitamin K.

(5) To reduce the potential for error, only oral unit dose products, pre-filled syringes and pre-mixed infusion bags will be used for anticoagulant medications when these products are available.

(a) Oral unit dose warfarin will be dispensed in the most ready-to-administer dosage forms and package sizes. If tablet splitting is required to achieve the required warfarin dose, the split tablet will be packaged by pharmacy and the package label will note that one-half tablet equals the dose.

(b) Pre-filled syringes will be used for LMWH and anti-Xa inhibitors.

(c) UFH infusion is available only as a pre-mixed bag containing 25,000 units in 250ml D5W. Heparin infusion rates require a double check per Nursing Policy #81.

Heparin infusion must be administered using a programmable infusion pump. No other fluids are to be infused on the same pump as heparin which will be infused via the primary line. Other solutions and medications may be administered through the same site as heparin but must be on a separate infusion pump. The only exceptions to this policy are in the Surgery Intensive Care Unit (SICU), Coronary Care Unit (CCU), Medical Intensive Care (MICU) and 5E Cardiac Step-down units which have been approved to administer heparin on a programmable pump with other infusions if

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no compatibility issue exists. If the patient is transferred out of one of these areas into an area where this exception does not exist, the infusion will be changed so that the heparin is the primary infusion on a separate pump.

(d) Because injectable DTI (e.g. argatroban, lepirudin and bivalirudin) are typically used to replace heparin in patients with HIT, the administration safety precautions for heparin apply. DTI intravenous infusions will be prepared by pharmacy and dispensed in ready-to-administer form. DTI infusion rates require a double check per Nursing Policy #81. DTI infusion must be administered using a programmable infusion pump. No other fluids are to be infused on the same pump as a DTI which will be infused via the primary line. Other solutions and medications may be administered through the same site as a DTI but must be on a separate infusion pump. The only exceptions to this policy are in the SICU, CCU, MICU and 5E Cardiac Step-down units which have been approved to administer a DTI on a programmable pump with other infusions if no compatibility issue exists. If the patient is transferred out of one of these areas into an area where this exception does not exist, the infusion will be changed so that the DTI is the primary infusion on a separate pump.

d. In the outpatient setting:

(1) The AMTP will monitor and adjust the anticoagulation therapy based established dosing and monitoring protocols. The appropriate ICD10 code to indicate warfarin monitoring will be included on the patient's problem list in CPRS (e.g-Z.79.01 Long-term (current) use of anticoagulants).

(2) Interpretation of the laboratory results will be based on the latest ACCP Consensus Conference on Antithrombotic Therapy and the clinical judgment of the pharmacist.

Follow up monitoring will be scheduled in accordance with ACCP recommendations.

For a patient whose INR is within the therapeutic range, repeat follow up should be scheduled at a maximum of 6 weeks at the discretion of the provider and patient preference. Patient's whose INR is outside the target range should be rescheduled more frequently depending on the amount of deviation from the target range and stability of the patient. All none critical INRs should be evaluated in a timely manner by the close of the next business day (or within 48 hours) and in accordance with VHA Directive 1033. Critical INRs must be evaluated and acted upon within 24 hours of the critical INR result with appropriate documentation of actions.

(3) Documentation of laboratory results will be done in CPRS. Patients will be encouraged to have laboratory done at the CAVHS or CBOC laboratories for consistency of testing. Patients who are unable to have routine testing done at either CAVHS or a CBOC laboratory may opt to have laboratory done by a remote or non-VA laboratory with results sent to the ATMP for review and management by the clinic staff.

These tests will be verified for accuracy and documented in the medical record via progress note. Documentation of outside lab will include the name, address and phone number of the lab performing the test, the date the test was drawn and the reference range of the test.

(4) The ATMP or Primary Care Provider will perform an assessment of the risk to benefit of anticoagulation at least annually, and will document this assessment in the

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patient's medical record. At any time, the risk of warfarin outweighs the benefit, the pharmacist will collaborate with the patient's primary care provider to determine appropriate course of action. Risk factors may include compliance issues as well as concomitant disease states.

(5) When a patient has completed the predetermined anticoagulation treatment duration or the risk of anticoagulation is determined to outweigh the benefit, the clinical pharmacist will collaborate with the patient's primary care provider to discontinue therapy. At such time, appropriate documentation will be made in CPRS and the ICD10 code indicating current anticoagulation will be removed.

(6) Patients and their caregivers will be provided education that includes the importance of follow up monitoring, compliance, dietary restrictions and the potential for adverse drug reactions and interactions. In addition, they will be educated regarding warfarin tablet identification, indication for therapy, drug, diet and disease interactions, daily dosage, monitoring requirements, the importance of medication adherence, the dangers of using warfarin from different sources, the management of missed doses, the signs and symptoms of bleeding and thromboembolic events and the risks associated with falling. Patients and their caregivers may also be provided education regarding injection technique if appropriate. Documentation of education will be made in CPRS using approved progress note templates or clinical reminders.

(7) The clinical dietitian will respond according to established food and medication interaction protocols designed to promote steady vitamin K intake in patients on warfarin who receive meal services. Meal plans and patient dietary education will be individualized to meet overall health needs supporting an adequate dietary Reference Intake for vitamin K.

(8) The clinical dietitian will be responsible for developing and implementing warfarin education material that follows requirements outlined in MCM 142A-2 Selection of Educational Resources for Patient and Family Health Education.

(9) The ATMP will develop and communicate a plan to the patient and next provider of care as well as provide follow up for bridge therapy when warfarin is intentionally held as when a patient is scheduled for an invasive procedure or when the INR level falls below the therapeutic level (Attachment C). Referrals for bridge therapy may be made to the ATMP through the consult process. The anticoagulation therapy provider completing the consult is responsible for suspending and restarting anticoagulation therapy with input from surgery and or primary care provider as needed.

(10) To reduce the potential for error, unless clinically inappropriate:

(a) Warfarin and direct oral anticoagulant prescriptions will be limited to a 90-day supply to prevent patients from continuing to obtain either of these medications without proper monitoring.

(b) Patients will be supplied only one tablet strength of warfarin.

(c) Patients will be provided written instructions whenever a dose change is made and the warfarin prescription will be updated accordingly.

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(d) Prescriptions for anticoagulant medications will not be written for patients who choose to have their anticoagulant therapy managed by providers outside the VA or choose to participate in self-monitoring programs.

(11) The potential for patient harm when a critically interacting drug is added to a patient stabilized on warfarin therapy is high. To reduce this risk, the ATMP will print a list of these critical interactions for review and development of an appropriate action plan. This review will occur no less often than every 96 hours on an ongoing basis. As the effects of interacting drugs are often delayed, are unpredictable and patient specific, typical management strategies include temporary alteration of the warfarin dose, increased INR monitoring or both. Documentation of communication between the ordering provider and the anticoagulant clinic provider will be through progress note.

(a) Anticoagulation safety practices are evaluated through a comprehensive, continuous quality assurance and improvement process administered by the ATMP.

Actions to improve practice are implemented and evaluated with follow up measures to determine the effectiveness of these actions on a regular basis. Ongoing monitors include INRs above the critical value including appropriate action within 24 hours, bleeding events, thromboembolic events unintentional sub therapeutic INRs and incident reports to include near miss and close calls.

(b) Documentation of patient education and management will be made in the patient medical record using approved progress note templates and clinical reminders.

5. REFERENCES:

a. Nursing Policy and Procedure #81.

b. The Joint Commission Accreditation Manuals for Hospitals, Ambulatory Care, Behavioral

Health Care and Home Care 2017.

c. Consensus Guidance to Insure the Safe Use of Anticoagulants. July 2008. National VA Hi-Alert Anticoagulant Workgroup, VHA Pharmacy Benefits Management Services, and the Medical Advisory Panel.

d. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report.

2016;149(2):315-352.

e. Guyatt GH, et al. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST.

2012;141(2_suppl):1S-801S.

f. Gage BF, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864-70.

g. Douketis JD, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation.

NEJM. 2015; 373:823-833.

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h. Clark NP, et al. Bleeding, recurrent venous thromboembolism, and mortality risks during warfarin interruption for invasive procedures. JAMA Intern Med. 2015;175(7):1163-68.

i. Ansell J. Hirsh J. Hylek E. et. al. Pharmacology and management of vitamin K antagonists: the American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008; 133:160-198.

j. Anticoagulation Therapy Management, VHA Directive 1033, July 2015 (replaces VHA

Directive 2010-020. May, 2010) Department of Veterans Affairs, Veterans Health Administration.

k. Guidance for the Oversight and Monitoring of Direct Oral Anticoagulants (DOACs)

(formerly called TSOACs). VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacists Executives. December 2016.

l. Medical Center Memorandum 142A-2, Selection of Educational Resources for Patient and Family Health Education.

m. Blood.2012;120(15):2954-2962)

/s/

MARGIE A. SCOTT, M.D.

Medical Center Director

Attachments

A-1

MEMORANDUM NO. 11-36 – ATTACHMENT A

B-1

MEMORANDUM NO. 11-36 – ATTACHMENT B

Recommendations for Managing Elevated INRs or Bleeding in Patients Receiving Warfarin

(Based on 2012 CHEST Guidelines):

INR Action

INR < 4.5 -Reduce dose or omit warfarin dose

-May or may not need to decrease weekly dose

INR 4.5-10 with no evidence of bleeding

-Hold warfarin

-No vitamin K necessary

-May or may not need to decrease weekly dose

INR > 10 with no evidence of bleeding -Hold warfarin

- Administer oral vitamin K (phytonadione) 5mg

Warfarin-associated major bleeding at any INR value

-Hold warfarin

-Vitamin K 5-10mg slow IV infusion with four-factor prothrombin complex concentrate (PCC), recombinant factor VIIa, or fresh frozen plasma

If continuing warfarin therapy is indicated after high doses of vitamin K, then heparin or low molecular weight heparin may be given until the effects of vitamin K have been reversed (see

Warfarin Interruption Guidelines, Attachment C), and the patient becomes responsive to warfarin therapy.

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MEMORANDUM NO. 11-36 – ATTACHMENT C

CAVHS Enoxaparin Bridging Protocol

A. Patients on anticoagulant therapy who require normalization or a reduction in intensity of anticoagulant effect prior to surgery or a procedure will need to withhold warfarin or other oral anticoagulant therapy for 5 days prior to the surgery or procedure. In addition, an evaluation to determine if peri-procedural bridging anticoagulation is required must be done.

B. Determination of thrombosis risk is accomplished using the following table:

Risk Stratification for Peri-Procedural Interruptions of Warfarin

“Bridging” with parenteral anticoagulants significantly increases the risk of bleeding, but has not been shown to reduce thromboembolic events. Given the lack of data indicating a net clinical benefit of bridging, we suggest NOT bridging most patients. Bridging would generally not be recommended for low-moderate risk patients, as defined in the table below. Clinicians may consider bridging for high-risk patients, but bridging should not be considered automatic even for high-risk patients, and should always be decided on a case-by-case basis. When selecting a parenteral agent for patients with decreased renal function or ESRD, use clinical judgement (heparin versus enoxaparin).

Indication for Anti-thrombotic Bridging Therapy

TE Risk

Level

Mechanical Heart

Valve

AF VTE1

High (>10% annual risk for

TE)

• Any mitral mechanical valve

• Any mechanical valve with history of stroke, TIA, systemic embolism, or valve thrombosis occurring with prior interruption, or while on therapy

• Any Older (caged ball or tilting disc) valve prosthesis

• CHADS2 score2 5 or 6, if prior stroke was cardioembolic

• Prior stroke, TIA, or systemic embolus in the last 3 months

• History of stroke, TIA, or systemic embolus occurring with prior interruption, or while on therapy

• Recent VTE

(within last 3 months)

• VTE with anti-phospholipid antibody syndrome

• VTE with active cancer3 for the following high thrombotic risk cancer types: pancreatic, CNS, GI, lung, endocrine, head/neck4

• History of recurrent VTE during short-term interruption of anticoagulant therapy, in a patient planning to undergo a high thrombotic risk procedure

1 Prophylactic-dose LMWH is a reasonable choice for preventing venous thromboembolism in some patients, especially those whose risk-benefit balance is a close call. Prophylactic-dose LMWH would be an ineffective strategy to prevent arterial TE, and is not recommended in that context.

2 CHADS2 score is used over CHA2DS2-VASC as there is no data to support its use for perioperative risk stratification regarding bridge therapy. It is up to the discretion of providers to use CHA2DS2-VASC for risk stratification.

3 Active cancer is defined as ongoing treatment, treatment completed within the past 6 months, or palliative intent.

4 Thromb Haemost 2010; 103: 338–343.

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MEMORANDUM NO. 11-95 – ATTACHMENT C

Risk Stratification for Peri-Procedural Interruptions of Warfarin

“Bridging” with parenteral anticoagulants significantly increases the risk of bleeding, but has not been shown to reduce thromboembolic events. Given the lack of data indicating a net clinical benefit of bridging, we suggest NOT bridging most patients. Bridging would generally not be recommended for low-moderate risk patients, as defined in the table below. Clinicians may consider bridging for high-risk patients, but bridging should not be considered automatic even for high-risk patients, and should always be decided on a case-by-case basis. When selecting a parenteral agent for patients with decreased renal function or ESRD, use clinical judgement (heparin versus enoxaparin).

Indication for Anti-thrombotic Bridging Therapy

TE Risk

Level

Mechanical Heart

Valve

AF VTE1

Low-

Moderate

(<10% annual risk of TE)

• Any patient with mechanical heart valve, AF, or VTE not specified above.5

C. Presence of a history of heparin induced thrombocytopenia (HIT) and bleeding risk must be ruled out.

D. Estimate patient's Creatinine Clearance in patients at high risk for thrombosis.

E. The following guidelines are recommended but should be modified to individualized therapy taking into account the overall risk of bleeding from the procedure with the underlying risk for thrombosis as well as patient preferences and renal function:

5 While treatment-dose bridging is generally not recommended in this category, prophylactic-dose LMWH may be considered for patients who experienced unprovoked VTE between 3-12 months ago, depending on clinical judgment. Prophylactic-dose LMWH would be an ineffective strategy to prevent arterial TE, and is not recommended in that context.

C-3

HIGH Moderate Low

Continue dual antiplatelet therapy around time of surgery instead of stopping 7-10 days prior (caution for high bleeding risk procedure/pts) [Grade 2C]

Continue dual antiplatelet therapy around time of surgery instead of stopping 7-10 days prior (caution for high bleeding risk procedure/pts) [Grade 2C]

Continue dual antiplatelet therapy around time of surgery instead of stopping 7-10 days prior (caution for high bleeding risk procedure/pts) [Grade 2C]

Stop warfarin 5 days prior

[Grade 1C]

Stop warfarin 5 days prior

[Grade 1C]

Bridging/No bridging is based upon individual pt and surgery related factors

Stop warfarin 5 days prior

[Grade 1C]

Enoxaparin 1mg/kg twice daily starting 4 days prior in patient with CrCl >30ml/min (round up to nearest whole syringe). In pts with reduced renal function

(CrCl < 30ml/min) dose reduction is required with a

1mg/kg daily dose as an option.

[Grade 2C]

Enoxaparin 1mg/kg twice or

40mg daily starting 4 days prior in pt w/CrCl >30ml/min (round down to nearest whole syringe).

In pts with reduced renal function (CrCl < 30ml/min) dose reduction is required with a

1mg/kg daily dose as an option or fixed dose 40mg daily

No bridging or enoxaparin 40mg daily [Grade 2C]

Draw INR 1-2 days prior and give Vitamin K 1-2.5mg if

INR≥1.5

Draw INR 1-2 days prior and give Vitamin K 1-2.5mg if

INR≥1.5

Draw INR 1-2 days prior and give Vitamin K 1-2mg if INR≥1.5

Administer last dose of enoxaparin 24 hours prior to procedure

Administer last dose of enoxaparin 24 hours prior to procedure

Resume enoxaparin 12-24 hours after a minor surgical procedure; 48 to 72 hours after major surgery when post-op hemostasis is adequate

Resume enoxaparin 12-24 hours after a minor surgical procedure; 48 to 72 hours after major surgery when postop hemostasis is adequate

Resume antiplatelets 24 hours after procedure if stopped.

Resume antiplatelets 24 hours after procedure if stopped.

Resume antiplatelets 24 hours after procedure if stopped.

C-4

Resume warfarin 12 to 24 hours after at previous dose

Resume warfarin 12 to 24 hours after at previous dose

Resume warfarin 12 to 24 hours after at previous dose

Check INR at 4 to 7 days after restarting warfarin to determine if enoxaparin can be discontinued

Check INR at 4 to 7 days after restarting warfarin to determine if enoxaparin can be discontinued

Check INR at 4-7 days after restarting warfarin

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MEMORANDUM NO. 11-36 – ATTACHMENT D

Preoperative interruption of new oral anticoagulants: a suggested management approach Adapted from Table 4, Blood.2012;120(15):2954-2962.

Drug (dose) * Patient renal function Low bleeding risk surgery (2 or 3 drug half-lives between last dose and surgery)

High bleeding risk surgery ++ (4 or 5 drug half-lives between last dose and surgery)

Dabigatran (150mg twice daily) t 1/2 = 14-17 hours Normal or mild impairment (CrCl >50 mL/min)

Last dose: 2 days before surgery (Skip 2 doses)

Last dose 3 days before surgery (skip 4 doses) t 1/2 = 16-18 hours Moderate impairment (CrCl 30-50 mL/min)

Last dose: 3 days before surgery (Skip 4 doses)

Last dose 4-5 days before surgery (skip 6-8 doses)

Rivaroxaban (20 mg once daily) t 1/2 = 8-9 hours Normal or mild

(CrCl >50 mL/min)

Last dose: 2 days before surgery (Skip 1 dose)

Last dose 3 days before surgery (skip 2 doses) t 1/2 = 9 hours Moderate impairment (CrCl 30-50 mL/min)

Last dose: 3 days before surgery (Skip 1 dose)

Last dose 3 days before surgery (skip 2 doses) t 1/2 = 9-10 hours Severe impairment $ (CrCl 15-29.9 mL/min)

Last dose: 3 days before surgery (skip 2 doses)

Last dose: 4 days before surgery (skip 3 doses)

Apixaban (5 mg twice daily) t 1/2 = 7-8 hours Normal or mild

(CrCl >50 mL/min)

Last dose: 2 days before surgery (Skip 2 doses)

Last dose 3 days before surgery (skip 4 doses) t 1/2 = 17-18 hours Moderate impairment (CrCl 30-50 mL/min)

Last dose: 3 days before surgery (Skip 4 doses)

Last dose 4-5 days before surgery (skip 6 doses)

* Estimated t 1/2 based on renal clearance

+ Aiming for mild or moderate residual anticoagulant effect at surgery (<12%-25%)

++ Aiming for no or minimal residual anticoagulant effect (<3%-6%) at surgery.

$ Patients receiving rivaroxaban, 15 mg once daily

D-2

MEMORANDUM NO. 11-36 – ATTACHMENT D

Postoperative resumption of New Oral Anticoagulants: A suggested management approach Adapted from Table 5, Blood.2012;120(15):2954-2962.

Drug Low Bleeding Risk Surgery High Bleeding Risk Surgery

Dabigatran Resume on day after surgery (24 hour postoperative), 150 mg twice daily

Resume 2-3 days after surgery (48-72 hours postoperative), 150mg twice daily*

Rivaroxaban Resume on day after surgery (24 hour postoperative) , 20 mg daily

Resume 2-3 days after surgery (48-72 hours postoperative), 20mg daily +

Apixaban Resume on day after surgery (24 hour postoperative), 5 mg twice daily

Resume 2-3 days after surgery (48-72 hours postoperative), 5 mg twice daily +

* For patients at high risk for thromboembolism, consider administering a reduced dose of dabigatran (eg, 110-150 mg once daily) on the evening after surgery and on the following day (first postoperative day) after surgery + Consider a reduced dose (ie, rivaroxaban 10mg once a day or apixaban 2.5 mg twice a day) in patients at high risk for thromboembolism.

Recommended Laboratory Testing on ER Admission8

• Hemoglobin

• Platelet count

• Serum creatinine

• LFTs

• aPTT

• INR

• Fibrinogen activity

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MEMORANDUM NO. 11-36 – ATTACHMENT E

Table 1: Reversal of ORAL anticoagulants

Rivaroxaban (Xarelto®)

• Stop medication

• General supportive measures

Considerations if no contraindication present:

1. Activated charcoal if within 2 hours of ingestion

PT (reagent dependent) aPTT (reagent dependent) Xa

Medication Available Treatment Coagulation Assay

Apixaban (Eliquis®)

• Stop medication

• General supportive measures

Considerations if no contraindication present:

1. Activated charcoal if within 2 hours of ingestion

• 10:1 ratio (activated charcoal:apixaban dose)

2. 4-factor PCC (Kcentra)

• 50 units/kg

• Limited evidence to support efficacy; weigh risk of increased thrombosis vs benefit of treatment

3. Activated PCC (FEIBA)

• 50 units/kg IV; may require repeat dose after 6 hours if bleeding persists

4. rfVIIa (Novoseven)

• 20 International units/kg; may repeat every 2 hours

• Limited and conflicting data to support use; weigh risk of increased thrombosis versus benefit of treatment

5. Hemodialysis not studied

6. FFP NOT recommended

PT (reagent dependent) aPTT (reagent dependent) Xa

Dabigitran (Pradaxa®)

• Stop medication

• General supportive measures

Considerations if no contraindication present:

1. Idarucizumab, (Praxbind)

• 5 grams (two doses of 2.5 grams/50 mL)

• Manufacturer recommends monitoring aPTT, or ecarin clotting time (ECT)

2. Activated charcoal if 2 hours of ingestion

• 10:1 (activated charcoal:dabigatran dose)

3. Hemodialysis may be considered for reversal

4. Activated PCC (FEIBA) units/kg IV once; may repeat 50 units/kg in 6-12 hours if bleeding persists

5. 4-factor PCC (Kcentra)

• 50 units/kg

• Limited evidence to support efficacy; weight risk of increase thrombosis vs benefit of treatment

6. rfVIIa (consider for refractory bleeding)

• 90 mcg/kg once aPTT (reagent dependent)

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Rivaroxaban (Xarelto®) continued

• 10:1 (activated charcoal:rivaroxaban dose)

2. 4-factor PCC (Kcentra): limited evidence to support efficacy;

weigh risk of increase thrombosis vs benefit of treatment

• 50 units/kg

3. Activated PCC (FEIBA)

• 20 - 40 units/kg IV; may require repeat dose after 6 hours if bleeding persists

4. rfVIIa (Novoseven)

• 20 International units/kg; may repeat every 2 hours

• Limited and conflicting data to support use; weigh risk of increased thrombosis versus benefit of treatment

5. Hemodialysis not studied

6. FFP NOT recommended

Limited evidence to support efficacy; weigh risk of increased thrombosis versus benefit of treatment

*PCC: Prothrombin complex concentrates, rfVIIa: recombinant factor VIIa, FFP: fresh frozen plasma

Table 2: Protamine dose for reversal of heparin and LMWH

Agent Half-life Protamine sulfate dosing for reversal

Heparin 1 – 2 hours 1 mg per 100 units heparin in previous 2 – 3 hours

Enoxaparin 4.5 hours 1 mg per 1 mg enoxaparin in previous ≤ 8 hours

0.5 mg per 1 mg enoxaparin in previous 8 – 12 hours Not effective if >12 hours

A second infusion of 0.5 mg protamine sulfate per 1 mg of enoxaparin may be administered if the aPTT measured 2 to 4 hours after first infusion remains prolonged.

Dalteparin 2.2 hours 1 mg per 100 units dalteparin in previous 8 hours

Tinzaparin 3.9 hours 1 mg per 100 units tinzaparin in previous 8 hours

Maximum protamine dose is 50 mg

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Table 3: Reversal of parenteral anticoagulants

Agent Treatment/Reversal Agent Coagulation Assay

Argatroban aPTT; will elevate INR

Bivalirudin aPTT

Dalteparin3 Protamine (see Table 3) aFXa

Enoxaparin4 Protamine (See Table 3) aFXa

Fondaparinux5 Consider hemodialysis aFXa

UFH Protamine aPTT

REFERENCES

1. Ray B and Keyrouz SG. Management of anticoagulant-related intracranial hemorrhage:

an evidence-based review Critical Care 2014;18:223.

2. Siegal DM and Crowther MA. Acute management of bleeding in patients on novel oral anticoagulants Eur Heart J 2013;34:489-500.

3. FEIBA NF® (anti-inhibitor coagulant complex) [package insert]. Westlake Village, CA;

Baxter; Revised February 2011.

4. Kcentra® (Prothrombin complex concentrate) [package insert]. Kanakee, IL;Behring LLC;

Revised 2013.

5. Miller, M. et. al. (2014). Practical Considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants. American Journal of Emergency

Medicine 32: 375-382.

6. Gonsalves WI, Gupta V, Patnaik MM. Management of bleeding complications in patients on new anticoagulants. J Hematol Transfus 2014:2(1):1-6.

7. Kreuziger LM, Keenan JC, Morton CT, et al. Management of the bleeding patient receiving new oral anticoagulants: a role for prothrombin complex concentrates. Biomed

Research International 2014;1-7.

8. Riley TT, Sanchez CK, Riley TR. Reversal of new anticoagulants in acute hemorrhagic stroke. US Pharm. 2014;39(1):HS2-HS.

9. Fragmin® (dalteparin) [prescribing information]. Eisai and Pfizer. 2010.

10. Lovenox® (enoxaparin) [prescribing information]. Sanofi‐Aventis US. 2011.

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11. Arixtra® (fondaparinux) [prescribing information]. 2011 https://www.gsksource.com/gskprm/htdocs/documents/ARIXTRA‐PI‐PIL.PDF

12. Idarucizumab (Praxbind) prescribing information

13. Practice guide on anticoagulant dosing and management of anticoagulant associated bleeding complications in adults. American Society of Hematology 2011.

www.hematology.org https://www.gsksource.com/gskprm/htdocs/documents/ARIXTRA‐PI‐PIL.PDF http://www.hematology.org/

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Guidelines for anticoagulation reversal and management of bleeding complications:

Table 1: Available agents and pharmacokinetic properties

ORAL

Medication Class Route Half-Life (t 1/2) Metabolism Excretion

Apixiban (Eliquis®)

Xa inhibitor

PO 8 - 15 hours

Hepatic/CYP450/P-gp substrate

Partially renal/fecal

Dabigatran (Pradaxa®)

DTI PO 12 – 17 hours

Elderly: 14 - 17 hours Mild-moderate RI: 15

- 18 hours Severe RI: 28 hours

N/A Renal (80%)

Rivaroxaban (Xarelto®)

Xa inhibitor

PO 5 – 9 hours

Elderly 11 – 13 hours

Hepatic/CYP450 Partially renal/hepatobiliary

Warfarin (Coumadin®)

VKA PO 24 – 72 hours Hepatic/CYP450 Renal (92%)

PARENTERAL

Argatroban DTI IV 30 – 51 minutes HI: < 181 min

Hepatic Fecal/biliary/partially renal

Bivalirudin (Angiomax®)

DTI IV 25 minutes (in normal renal function – CrCl > 90ml/min)

Proteolytic cleavage Renal/proteolytic cleavage

Dalteparin (Fragmin®)

LMWH SQ

3 – 5 hours

Chronic RI: 3.7 – 7.7 hours

N/A Renal

Enoxaparin (Lovenox®)

LMWH IV/SQ

(IV:

STEMI/PCI

use only)

3 – 7 hours

Hepatic (minor) Renal

Fondaparinux (Arixtra®)

Xa inhibitor

SQ 17 – 21 hours (Prolonged in RI)

N/A Renal (77%)

Heparin

Heparin IV 30 – 60 minutes

Dose dependent:

25 units/kg: 30 min 100 units/kg: 60 min 400 units/kg: 150 min Mean: 1.5 hours

Hepatic/partially reticuloendothelial

Non-renal (at therapeutic doses, high doses renal elimination more significant)

*RI: renal impairment, HI: hepatic impairment, CYP450: cytochrome P450 enzyme system, DTI:

direct thrombin inhibitor, LMWH: low molecular weight heparin, VKA: vitamin K antagonist

F-1

MEMORANDUM NO. 11-36 – ATTACHMENT F

WEIGHT BASED HEPARIN PROTOCOLS

The following guidelines are recommended but should be modified to individual therapy taking into account the overall risk of bleeding from the procedure with the underlying risk for thrombosis as well as patient preference. Nursing titration orders will be used in the Critical Care and Step-down units. Providers must enter heparin orders for all other units.

IMPORTANT: if the patient needs hypercoaguable work-up the blood should be drawn before the warfarin or heparin bolus is administered Baseline Platelet count____________ Baseline aPTT ____________ patient weight _______________Kg (actual)

1. Draw INR, aPTT, Platelet count and CBC stat (prior to bolus dose if not done in prior 24 hours)

2. aPTT 6 hours after heparin bolus (run results stat)

3. Draw aPTT at frequency based on heparin dosage adjustment chart

4. Based on aPTT results, adjust heparin administration rate according to heparin dosage adjustment chart

5. Document heparin rates, changes and aPTT times in the medical record

6. CBC and check platelet count every other day. If platelet count drops to <50% of baseline or drops to < 150,000/mcL notify physician Immediately for suspected HIT.

7. Assess for signs of bleeding; urine, stool, skin, emesis, change in mental status. If signs of bleeding, notify physician.

8. If a aPTT is within therapeutic range for 2 consecutive draws, draw a aPTT every 24 hours until out of therapeutic range, or as deemed appropriate by provider.

60units/kg bolus; 12units/kg/hr (max bolus 4000units; max rate 1000units/hr) Cardiology Heparin 25000units/D5W 250ml (100units/ml) Heparin 1000units/ml 10ml vial for bolus doses

Weight (kg)

Initial Bolus

Initial Rate aPTT < 35 aPTT 35-49.9 aPTT 50-75 aPTT 75.1-100 aPTT >100

Bolus Dose

Increase Rate by

Bolus Dose

Increase Rate by

Hold For

Decrease Rate by

Hold for

Decrease Rate by

50 3000units 600units/hr 3000units 150units/hr 1500units 50units/hr No change --- 50units/hr 60min 100units/hr

55 3500units 650units/hr 3500units 150units/hr 1650units 50units/hr No change --- 50units/hr 60min 100units/hr

60 3500units 700units/hr 3500units 200units/hr 1800units 50units/hr No change --- 50units/hr 60min 100units/hr

65 4000units 800units/hr 4000units 200units/hr 1950units 50units/hr No change --- 50units/hr 60min 150units/hr

70 4000units 850units/hr 4000units 200units/hr 2000units 50units/hr No change --- 50units/hr 60min 150units/hr

75 4000units 900units/hr 4000units 250units/hr 2250units 100units/hr No change --- 100units/hr 60min 150units/hr

80 4000units 950units/hr 4000units 250units/hr 2400units 100units/hr No change --- 100units/hr 60min 150units/hr

85 4000units 1000units/hr 4000units 250units/hr 2500units 100units/hr No change --- 100units/hr 60min 150units/hr

90 4000units 1000units/hr 4000units 250units/hr 2500units 100units/hr No change --- 100units/hr 60min 150units/hr

95 4000units 1000units/hr 4000units 300units/hr 2500units 100units/hr No change --- 100units/hr 60min 200units/hr

100 4000units 1000units/hr 4000units 300units/hr 2500units 100units/hr No change --- 100units/hr 60min 200units/hr

105 4000units 1000units/hr 4000units 300units/hr 2500units 100units/hr No change --- 100units/hr 60min 200units/hr

110 4000units 1000units/hr 4000units 350units/hr 2500units 100units/hr No change --- 100units/hr 60min 200units/hr

115 4000units 1000units/hr 4000units 350units/hr 2500units 100units/hr No change --- 100units/hr 60min 250units/hr

120 4000units 1000units/hr 4000units 350units/hr 2500units 100units/hr No change --- 100units/hr 60min 250units/hr

F-2

WEIGHT BASED HEPARIN PROTOCOLS

The following guidelines are recommended but should be modified to individual therapy taking into account the overall risk of bleeding from the procedure with the underlying risk for thrombosis as well as patient preference. Nursing titration orders will be used in the Critical Care and Step-down units. Providers must enter heparin orders for all other units.

IMPORTANT: if the patient needs hypercoaguable work-up the blood should be drawn before the warfarin or heparin bolus is administered Baseline Platelet count____________ Baseline aPTT ____________ patient weight _______________Kg (actual)

1. Draw INR, aPTT, Platelet count and CBC stat (prior to bolus dose if not done in prior 24 hours)

2. aPTT 6 hours after heparin bolus (run results stat)

3. Draw aPTT at frequency based on heparin dosage adjustment chart

4. Based on aPTT results, adjust heparin administration rate according to heparin dosage adjustment chart

5. Document heparin rates, changes and aPTT times in the medical record

6. CBC and check platelet count every other day. If platelet count drops to <50% of baseline or drops to < 150,000/mcL notify physician immediately for suspected HIT.

7. Assess for signs of bleeding; urine, stool, skin, emesis, change in mental status. If signs of bleeding, notify physician.

8. If a aPTT is within therapeutic range for 2 consecutive draws, draw a aPTT every 24 hours until out of therapeutic range, or as deemed appropriate by provider.

80units/kg bolus; 18units/kg/hr (max bolus 10,000units;)

DVT/PE Heparin 25000units/d5w 250ml (100units/ml) Heparin 1000units/ml 10ml vial for bolus doses

Weight (kg)

Initial Bolus

Initial Rate aPTT < 40 aPTT 40-64.9 aPTT 65-100 aPTT 100.1- 120 aPTT > 120

Bolus Dose

Increase Rate by

Bolus dose

Increase Rate by

Hold For

Decrease Rate by

Hold For

Decrease Rate by 50 4000units 900units/hr 4000units 200units/hr 2000units 100units/hr No change --- 100units/hr 60min 150units/hr

55 4500units 1000units/hr 4500units 200units/hr 2000units 100units/hr No change --- 100units/hr 60min 150units/hr

60 5000units 1100units/hr 5000units 250units/hr 2500units 100units/hr No change --- 100units/hr 60min 200units/hr

65 5000units 1150units/hr 5000units 250units/hr 2500units 150units/hr No change --- 150units/hr 60min 200units/hr

70 5500units 1250units/hr 5500units 300units/hr 2500units 150units/hr No change --- 150units/hr 60min 200units/hr

75 6000units 1350units/hr 6000units 300units/hr 3000units 150units/hr No change --- 150units/hr 60min 200units/hr

80 6500units 1450units/hr 6500units 300units/hr 3000units 150units/hr No change --- 150units/hr 60min 250units/hr

85 7000units 1550units/hr 7000units 350units/hr 3500units 150units/hr No change --- 150units/hr 60min 250units/hr

90 7000units 1600units/hr 7000units 350units/hr 3500units 200units/hr No change --- 200units/hr 60min 250units/hr

95 7500units 1700units/hr 7000units 400units/hr 3500units 200units/hr No change --- 200units/hr 60min 300units/hr

100 8000units 1800units/hr 8000units 400units/hr 4000units 200units/hr No change --- 200units/hr 60min 300units/hr

105 8500units 1900units/hr 8500units 400units/hr 4000units 200units/hr No change --- 200units/hr 60min 300units/hr

110 9000units 2000units/hr 9000units 450units/hr 4500units 200units/hr No change --- 200units/hr 60min 350units/hr

115 9000units 2050units/hr 9000units 450units/hr 4500units 250units/hr No change --- 250units/hr 60min 350units/hr

120 9500units 2150units/hr 9500units 500units/hr 5000units 250units/hr No change --- 250units/hr 60min 350units/hr

125 10000units 2250units/hr 9500units 500units/hr 5000units 250units No change --- 250units/hr 60min 400units/hr

130 10000units 2350units/hr 10000units 500units/hr 5000units 250units/hr No change ---…