S02 ATTACHMENT D.20 - SOP 011-116 MANAGEMENT OF ANTICOAGULATION THERAPY.pdf

Veterans Health Care System of the Ozarks (VHSO)

VHSO Memorandum Number 2018-11-116

March 19, 2019

Management of Anticoagulant Therapy

1. Purpose

To establish a defined anticoagulant management program, managed by providers trained and skilled in managing anticoagulant therapy, and to individualize the care provided to each patient receiving anticoagulant therapy.

2. Policy

It is the policy of this medical center to establish and adhere to criteria for initiation and maintenance of anticoagulation therapy appropriate to the medication used, to the condition being treated, and to the potential for drug interactions. The Veterans Health Care Systems of the Ozarks (VHSO) continuously assesses the safety of the anticoagulation practices and educates patients and their families about the importance of complying with all physician orders and instruction related to their anticoagulant medications, as well as possible side effects, food/drug interactions, and interactions with other medications. The Program consists of the following:

a. Development and implementation of medical center guidelines for treatment, education, and monitoring of anticoagulation patients.

b. Educational outreach efforts for clinical services to enhance compliance with practice guidelines.

c. Ensuring compliance with the safe use of anticoagulation therapy consistent with external oversight agency guidelines and Veterans Affairs (VA) policies such as:

(1) Use of only oral unit dose products, pre-filled syringes, or pre-mixed infusion bags for anticoagulant medications when these types of products are available in the inpatient setting.

(2) Use of programmable infusion pumps for intravenously administered heparin.

(3) Development and implementation of protocols for the initiation and maintenance of appropriate anticoagulation therapy, including, at a minimum (attached as appendices):

(a) Management of oral anticoagulation therapy during invasive procedures and peri-procedure bridge therapy.

(b) Heparin weight-based bolus and infusion dosing.

(c) Initiation and adjustment of warfarin therapy.

VHSO MCM 11-116

(d) Frequency of International Normalized Ratio (INR) testing.

(e) Management of supratherapeutic INRs or bleeding for patients on warfarin therapy.

(4) Use of baseline and ongoing laboratory tests as recommended by nationally published guidelines and as recommended in the product labeling as appropriate for the individual medication and patient. At minimum this should include:

(a) Baseline and Ongoing labs:

1) Heparin: Complete blood count (CBC) with platelets, and Activated Partial Thromboplastin Time (APTT).

2) Low Molecular Weight Heparins (LMWHs) and anti-Xa inhibitors (fondaparinux): CBC with platelets and serum creatinine.

3) Warfarin: CBC with platelets, Prothrombin Time (PT), and International Normalized Ratio (INR).

4) Direct Acting Oral Anticoagulant (DOAC): serum creatine (SCR), Creatine clearance (CrCl)

(5) A baseline INR is available prior to patients starting on anticoagulation therapy.

(6) A current INR is available in the electronic health record for all patients receiving anticoagulation therapy to monitor and adjust therapy, and a standardized process for documenting INR results received from a non-VA laboratory.

(7) A standardized process for documenting INR results received from a non-VA laboratory ensures they are readily retrievable and includes documentation of the name of the laboratory and the date of the test.

(8) Nutrition and Food Services notification and evaluation of all patients receiving warfarin and meal services according to an established food/medication interaction program.

(9) Completion of patient/family education for each patient that includes the importance of follow-up monitoring, compliance issues, dietary restrictions, and potential for adverse drug reactions and interactions. At a minimum, patient education needs to include warfarin tablet identification, indication for therapy, interactions (drug, diet, and disease), daily dosage, monitoring requirements, importance of medication adherence, the dangers of using warfarin from different sources (e.g. VA and community pharmacy), the management of missed doses, signs and symptoms of bleeding and Thromboembolic events, and risks associated with falling.

(10) Provision of education regarding anticoagulation therapy to all prescribers and staff involved in caring for patients receiving anticoagulation therapy. Point of Care supplies will not be provided by the facility. The facility will accept Point of Care test results provided by other agencies (i.e. home health agencies).

(11) On-going quality assurance plan with continuous monitoring of at least:

(a) INRs above the critical value

(b) Appropriate action has been taken on critical INRs within 24 hours of INR testing and documentation of action(s) taken

(c) Bleeding events

(d) Thromboembolic events

(e) Sub-therapeutic INRs

(f) Patient incidents and close-calls/near misses associated with anticoagulation

(12) Individualized care is provided to each inpatient and outpatient receiving anticoagulation therapy and provided for the coordinated transition of the patient from inpatient to outpatient status or outpatient to inpatient status. This process assures patients are followed-up appropriately and that the frequency of INR testing is performed according to the established protocol(s), as well as address patient no-shows for laboratory testing and clinic appointments, and patient non-compliance with the treatment plan.

(13) Mid-level practitioners involved in the management of anticoagulation therapy must have successfully completed a specialty training program in anticoagulation therapy management or be certified as an anticoagulation care provider (CAP), or complete an on-site anticoagulation training program that includes both experiential and didactic learning strategies.

(14) A defined process that ensures appropriate patient follow-up when a new drug that critically interacts with anticoagulants is added to the medication regimen of out-patients on anticoagulant therapy. This process should address adjustment of the anticoagulant dose if needed, order and needed any follow-up lab tests.

(15) The requirement to add Systematized Nomenclature of Medicine – Clinical Terms (SNOMED CT or SCT) 711150003 (International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM): R69) that denotes ‘Long-term (Current) Use of Anticoagulants’ to the problem list of outpatients on anticoagulant therapy.

(16) A defined process to minimize the risk associated with incorrect tablet strength dosing errors, in order that outpatients are supplied only one tablet strength of warfarin. Strategies may include:

(a) Limiting selection of warfarin strengths for outpatient prescriptions to 2 milligrams (mg) or 5mg tablets,

(b) Creating a separate outpatient orderable item for each warfarin tablet strength,

(c) Educating providers to always view the order in the Computerized Patient Record System, as it is built with emphasis on noting the tablet strength the software assigns based on the dose selected,

(d) Providing patient education with written instructions whenever a dosage change is made,

(e) Limiting outpatient warfarin ordering to select providers, and

(f) Using standardized quick order sets that promote uniformity of dosing.

d. Monitoring of quality assurance outcomes with follow-up.

3. Responsibilities

a. Medical Center Director. The facility Director is responsible for:

(1) Ensuring that a process for the safe management of anticoagulation therapy is in place.

(2) The medical center standardizes and limits (via the Pharmacy and Therapeutics Committee) the number of heparin concentrations available to meet patient care needs and no multi-dose heparin product more concentrated than 5,000 Units/ml is stocked without the prior approval of the Chief of Pharmacy.

b. Clinical Executives

Clinical Executives (Chief of Staff and Associate Director, Patient Care Services) are responsible for ensuring:

(1) A Scope of Practice and/or medical staff approved protocols are established for each anticoagulation provider that is not a Licensed Independent Practitioner (LIP).

(2) Programmable infusion pumps are in use for the intravenous administration of heparin.

(3) Inclusion of competencies specific for anticoagulation therapy management in the competency plans for clinical pharmacists, registered nurses, physician assistants, Advanced practice registered nurses involved in managing anticoagulation therapy. At minimum, competencies will include knowledge of the standard terminology, monitoring requirements, dose calculations, common side effects, dietary considerations, and drug/drug interactions associated with anticoagulation therapy.

(4) Assessment of the competency of mid-level medical and nursing staff practitioners involved in managing anticoagulation therapy.

(5) The Chief of Staff will serve as the Anticoagulation Program Manager Champion to lead the medical facility’s anticoagulation management program. This champion will serve collaboratively with the pharmacy anticoagulation champion to advocate for, provide consultation on anticoagulation issues and support anticoagulation initiatives at the facility level.

c. Chief Pharmacy Service

The Chief, Pharmacy Service is responsible for:

(1) Only oral unit dose products, pre-filled syringes, or pre-mixed infusion bags for anticoagulant medications are dispensed for inpatients when these types of products are available.

(2) The number of concentrations and quantities of heparin dosage forms stocked in patient care and procedural areas are limited to the minimum needed to meet patient care needs and no multi-dose heparin product more concentrated than 5,000 Units/ml is stocked without the prior approval of the Chief of Pharmacy.

(3) The safe storage of anticoagulants in automated dispensing devices. When multiple strengths or concentrations of the same anticoagulant are stored in the same automated dispensing device they should be stored in separate areas and clearly labeled as high alert medications.

(4) Anticoagulants are included on the medical center’s list of high-alert medications.

(5) Competencies specific for anticoagulation therapy management are included in the competency plans for mid-level pharmacy practitioners involved in managing anticoagulation therapy. At minimum, competencies will include knowledge of the standard terminology, monitoring requirements, dose calculations, common side effects, dietary considerations, and drug/drug interactions associated with anticoagulation therapy.

(6) Assessment of the competency of mid-level pharmacy practitioners involved in managing anticoagulation therapy.

(7) Pharmacy staff provides reviews (intervention) all critical drug interactions and appropriate indication.

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

(1) Warfarin is included in Nutrition and Food Service’s established food/medication interaction program.

(2) A process is established to notify Nutrition and Food Service of patients receiving meal services that are also receiving warfarin.

(3) Nutrition and Food Service responds according to its established food/medication interaction program to patients receiving meal services AND warfarin therapy. Meal planning and educational efforts are focused on steady vitamin K intake, individualized to meet the overall health needs, and supportive of an adequate dietary reference intake for Vitamin K.

e. Chief Pathology and Laboratory Medicine Service: The Chief, Pathology and Laboratory Medicine Service is responsible for:

(1) Evaluation of methods to document INRs done at non-VA labs in the electronic medical record and collaborating with outpatient anticoagulation therapy providers to identify and implement the safest method.

(2) A critical INR value being listed in the Laboratory Veterans Health Information Systems and Technology Architecture (Vista) software package.

(3) A Standard Operating Procedure for the communication of critical INR results from the laboratory to the provider.

(4) The correct International Sensitivity Index (ISI) value for the lot number of thromboplastin currently in use is entered into the coagulation testing instrumentation and there is documentation of periodic monitoring to assure the entered value remains accurate.

(5) The correct Geometric Mean PT is calculated for the current lot number of thromboplastin and is entered into the coagulation testing instrumentation as required for the calculation of the INR. The geometric mean PT should be recalculated with each change of lot number of thromboplastin reagent.

(6) Ensure the availability of appropriate laboratory tests for DOACs formerly known as Target Specific Oral Anticoagulants (TSOAC) in special situations (e.g.

suspected overdose, bleeding, urgent procedure, etc.).

f. Facility Anticoagulation Program Manager: The facility anticoagulation program manager is responsible for the following functions related to the anticoagulation program at the facility level:

(1) Serving as a leader or co-leader and subject matter expert in the oversight, design, implementation, and function of the anticoagulation management program.

(2) Developing medical facility policy related to use of anticoagulants. This encompasses policies to govern practice within the anticoagulation management program, but may also include policies relating to the use of anticoagulants in other areas (e.g., surgical or specialty areas), as directed by the Medical Executive Council.

(MEC) A multidisciplinary approach to policy development should be employed to include meeting with all disciplines involved in caring for patients receiving anticoagulants to assist with unified practice and education to patients.

(3) Promoting learning and unified practice for the anticoagulation management program through a variety of educational activities.

(4) Coordinating and reporting quality assurance activities and results for the anticoagulation management program through the Pharmacy and Therapeutics (P&T) Committee (or appropriate facility governing body) and MEC, as appropriate.

(5) Coordinating the facility educational program for clinical staff directly involved in caring for patients receiving anticoagulation therapy (e.g. clinical pharmacists, pharmacy technicians, registered dietitians/nutritionists, nurses, Advanced Practice Registered Nurse (APRN)s, physician assistants, and physicians).

(6) Ensuring availability of appropriate patient education materials and classes, as applicable.

g. Facility Providers with prescribing privileges: The facility providers with prescribing privileges are responsible for:

(1) Managing anticoagulation patients in accordance with facility and Veterans Health Administration (VHA) policy including, but not limited to, coordination of anticoagulation management for patients transitioning between care settings (e.g., inpatient to outpatient), peri-procedural anticoagulation, and traveling Veterans.

(2) Delivering initial and ongoing patient and family education that includes the importance of follow-up monitoring, compliance issues, dietary restrictions, and potential for adverse drug reactions and interactions.

(3) Conducting appropriate and periodic risk-benefit assessments for all patients receiving anticoagulant therapy and communicating recommendations to the original referring provider and/or Patient Aligned Care Team (PACT) provider as appropriate as established by the Facility Program Anticoagulation Manager.

(4) Performing and/or facilitating the day-to-day operations of the anticoagulation management program.

(5) Reporting, as per local policy, adverse drug events (ADE), close calls, and any unsafe conditions of which they are aware, even though the conditions have not yet resulted in an adverse event or close call to the facility Patient Safety Manager (PSM) in accordance with VHA Directive 1070, Adverse Drug Event Reporting and Monitoring, or subsequent policy issue.

h. Quality Assurance: An ongoing quality assurance must be in place to evaluate the anticoagulation management program. This provides the opportunity to identify practice improvements, ensures appropriate action is taken to improve the practice, and measures the effectiveness of those actions on a regular basis. The plan should include:

(1) Reports for tracking and trending of INR values at the National, Veterans Integrated Service Network (VISN), and facility levels;

Note: Reports should include those such as time in therapeutic range (TTR), proportion of patients on warfarin that have not had an INR in the last 42 days, or other reports that assess the quality of care provided at the facility level.

(2) Proportion of patients with pathologic bleeding events;

(3) Proportion of patients with thromboembolic events; and

(4) Patient incidents, close calls, and near misses associated with an anticoagulant. Adverse drug events (ADEs) involving anticoagulants should be assessed and analyzed in accordance with the facility P&T Committee and VHA Directive 1070, Adverse Drug Event Reporting and Monitoring, or subsequent policy issue.

Note: Appropriate capture of non-VA INR values and non-VA warfarin prescriptions, will greatly improve the accuracy of the quality assurance plan. The use of a health factor to capture such information is highly recommended.

i. Any identified issues found in the quality assurance program should be tracked and trended by the facility Anticoagulation Program Manager, or designee and reported through the Pharmacy & Therapeutics Committee to the MEC as appropriate.

4. References

a. VHA Directive 1108.06, Inpatient Pharmacy Services, dated 2/8/17

b. VHA Handbook 1108.05, Outpatient Pharmacy Services, dated 6/16/16

c. VHA Handbook 1106.01, Pathology and Laboratory Medicine Service Procedures, dated 1/29/16

d. Hospital National Patient Safety Goals - Joint Commission

e. VHA Directive 1033, Anticoagulation Therapy Management, dated 7/29/2015

f. Antithrombotic Therapy and Prevention of Thrombosis, 9th Education, Published:

February 2012.

g. Department of Veterans Affairs Pharmacy Benefits Management Services Criteria for Use of Fondaparinux

h. Department of Veterans Affairs Pharmacy Benefits Management Services Target Specific Oral Anticoagulants: Dabigatran, Rivaroxaban, and Apixaban Criteria for Use for Stroke Prevention in Nonvalvular Atrial Fibrillation (AF)

5. Rescissions: Medical Center Memorandum (MCM) 11-116 dated July 7, 2015.

http://www.jointcommission.org/standards_information/npsgs.aspx http://www.chestnet.org/Guidelines-and-Resources/CHEST-Guideline-Topic-Areas/Pulmonary-Vascular http://www.chestnet.org/Guidelines-and-Resources/CHEST-Guideline-Topic-Areas/Pulmonary-Vascular https://vaww.cmopnational.va.gov/cmop/PBM/Clinical%20Guidance/Forms/AllItems.aspx?RootFolder=%2Fcmop%2FPBM%2FClinical%20Guidance%2FCriteria%20For%20Use&FolderCTID=0x0120006BA3B2280F536A41A2C5A1B0F4AFC943&View=%7b43999405-C9A2-47A4-AE17-15518717FA3E%7d https://vaww.cmopnational.va.gov/cmop/PBM/Clinical%20Guidance/Forms/AllItems.aspx?RootFolder=%2Fcmop%2FPBM%2FClinical%20Guidance%2FCriteria%20For%20Use&FolderCTID=0x0120006BA3B2280F536A41A2C5A1B0F4AFC943&View=%7b43999405-C9A2-47A4-AE17-15518717FA3E%7d https://vaww.cmopnational.va.gov/cmop/PBM/Clinical%20Guidance/Forms/AllItems.aspx?RootFolder=%2Fcmop%2FPBM%2FClinical%20Guidance%2FCriteria%20For%20Use&FolderCTID=0x0120006BA3B2280F536A41A2C5A1B0F4AFC943&View=%7b43999405-C9A2-47A4-AE17-15518717FA3E%7d https://vaww.cmopnational.va.gov/cmop/PBM/Clinical%20Guidance/Forms/AllItems.aspx?RootFolder=%2Fcmop%2FPBM%2FClinical%20Guidance%2FCriteria%20For%20Use&FolderCTID=0x0120006BA3B2280F536A41A2C5A1B0F4AFC943&View=%7b43999405-C9A2-47A4-AE17-15518717FA3E%7d https://vaww.cmopnational.va.gov/cmop/PBM/Clinical%20Guidance/Forms/AllItems.aspx?RootFolder=%2Fcmop%2FPBM%2FClinical%20Guidance%2FCriteria%20For%20Use&FolderCTID=0x0120006BA3B2280F536A41A2C5A1B0F4AFC943&View=%7b43999405-C9A2-47A4-AE17-15518717FA3E%7d

6. Rescission: This VHSO Memorandum will expire on, or before the last working day of March 2024.

5/16/2019

X

Medical Center Director

Signed by: people

Attachments

1. Attachment A – Heparin Protocol

2. Attachment B – Heparin Infusion

3. Attachment C – Inpatient Warfarin Initiation Protocol

4. Attachment D – Outpatient Warfarin Initiation Protocol

5. Attachment E – Nomogram for Adjusting Warfarin Therapy Based on Total Weekly Dose

6. Attachment F – Recommendation for the Management of Subtherapeutic INRs and Bleeding Complications for Patients Receiving Oral Anticoagulation Therapy

7. Attachment G – Guidelines for Perioperative and Peri Procedure Management of Antithrombotic Therapy

8. Attachment H – Perioperative Management of Antithrombotic Therapy

9. Attachment I – Low Molecular Weight Heparin LMWH Treatment Use Guidelines

10. Attachment J – Direct Acting Anticoagulants Use Guidelines

Distribution: Via Intranet

Attachment A

Heparin Protocol

1. Weigh and record in kilograms

2. CBC, PT, Partial Thromboplastin Time (PTT), Liver, Renal Profile and prior to administering Heparin

3. CBC 24 hours after initiation of therapy, and every other day until day 14 or Heparin Therapy discontinued.

4. PT/PTT every morning x 3 days

5. Urinalysis

6. Heparin loading dose 65 units/Kg IV push (Round to nearest 1000 units) or alternate dose per MD.

7. Maintenance infusion to begin at 15 units/Kg/hr (round to nearest 100 units) continuous IV infusion or alternate dose as ordered by physician.

a. Adjust per sliding scale.

b. Check PTT 6 hrs after change.

c. If active bleeding occurs, stop Heparin, draw STAT CBC, PT, PTT and call Medical Doctor (MD).

8. Heparin sliding scale

a. Adjust Heparin infusion using sliding scale.

b. Check PTT 6 hours after any re-bolus or change in Heparin infusion until PTT is therapeutic, then PTT every morning.

PTT Re-bolus Change in Infusion Rate

Less than 40 80 units/kg Increase by 4 units/kg/hour

41-50 40 units/kg Increase by 2 units/kg/hour

51-80 No change

81-100 Decrease by 2 units/kg/hour

Greater than 100

Stop Heparin infusion for 1 hour. Resume after 1 hour and decrease rate by 3 units/Kg/Hour.

Attachment A

9. Warfarin mg PO daily to start on (date)

10. PT every AM beginning day 2 of Warfarin therapy

11. Call physician if infusion exceeds 2000 units per hour at any time. Physician will decide if rate can be increased above 2000 units/hr.

Signature/Title

Attachment B

Heparin Infusion

1. Purpose: To assure safe, accurate administration and consistent documentation of heparin by continuous infusion.

2. Policy: To provide a safe and efficient method of administering and titrating intravenous (IV) heparin via weight-based protocols. The Heparin Infusion Policy is implemented to ensure that staff follows the same process when delivering and documenting heparin infusions at VHSO. An initial verification of the dosage and pump setting, and each change of the heparin infusion bag or rate of infusion, will be performed by two Registered Nurses (RNs) before administering IV heparin.

3. Responsibility: RNs

4. Equipment: Manufacturer- premixed IV infusion bag of heparin, IV tubing set with free flow lock-out, and infusion pump.

a. Procedure: Licensed independent practitioners (LIPs) will order heparin infusion by using the Heparin Weight-based Protocol in Computerized Patient Record System

(CPRS).

b. Nursing staff is responsible for weighing the patient. The initial weight is used for all heparin dosing calculations.

c. The RN will ensure that baseline lab tests (i.e. Prothrombin Time (PT)/Partial Thromboplastin Time (PTT), Complete Blood Count (CBC)) are drawn prior to initiating the infusion except in the Emergency Department.

d. The RN will obtain the heparin pre-mixed infusion bag and scan it into Bar Code Medication Administration (BCMA). Using standard IV tubing and infusion pump guardrail system, two RNs will verify the patient, order, heparin dosage, and rate prior to attaching the tubing to the IV site as a primary infusion. A dedicated site is preferred.

5. Documentation

a. The RN initiating the infusion will enter a Heparin Infusion Note in the Computerized Patient Record System (CPRS). The verifying RN will sign the note as an additional signer. Heparin Worksheet may be utilized to assist with documentation and quality improvement monitoring.

b. A new Heparin Infusion Note will be entered at least daily and for any rate changes, after PTT draws or bolus doses ordered. The verifying RN will be named in the body of the note and added as an additional signer.

Attachment C

Inpatient Warfarin Initiation Protocol

These practice parameters are designed as guidelines and as such are not a substitute for the best professional judgment of physicians or other health professionals taking into consideration the individual circumstances presented by the patient. Acceptable medical practice may include a variety of responses to a particular clinical problem.

Warfarin Initiation

1. Obtain baseline laboratory values prior to starting warfarin, including:

a. CBC with platelets

b. Prothrombin time (PT)

c. International normalized ratio (INR)

2. Determine Appropriate Starting Dose of Warfarin

a. Consider patient-specific hemorrhagic risks vs. thrombotic risks.

b. The key to choosing the initial warfarin dose is evaluating patient factors that may affect warfarin sensitivity and responding appropriately to changes in INR. Select an initial dose that represents the maintenance dose the patient is most likely to require.

c. In patients beginning warfarin therapy, initiation may begin with doses between 5 and 10mg (5mg for most patients) for the first 1 or 2 doses with subsequent dosing based on the INR response (Grade 1B). In patients considered healthy enough to be treated as outpatients, 10mg daily for 2 days can be considered (Grade 2C). Loading (first) doses of > 10mg of warfarin are Not recommended.

d. A starting routine dose of ≤ 5mg (i.e. 2.5mg) is recommended in some populations (Grade 1C), among which include the following:

(1) Elderly (age > 60) or patients who are debilitated

(2) Elevated baseline INR

(3) High risk of bleeding

(4) Recent illness, including diarrhea &/or fever

(5) Recent major surgery

(6) Malnutrition, low albumin, or decreased oral intake (NPO > 3 days)

(7) Taking medications known to increase sensitivity to warfarin (i.e. amiodarone)

(8) Malignancy

(9) Congestive heart failure

(10) Liver dysfunction or renal failure

(11) Hyperthyroidism

(12) Low body weight (< 50 kg)

e. Younger patients with certain indications (i.e. deep vein thrombosis or pulmonary embolism) and less co-morbidity may receive larger starting routine doses as indicated.

3. Ongoing Monitoring and Education

a. INR daily until INR is within desired range for at least 2 consecutive days, then 2 to 3 times weekly for first 1-2 weeks, then less often depending on the stability of the INR results.

b. Monitor for signs of bleeding (at IV site, melena, hematuria, ecchymosis, hematemesis, and epistaxis).

c. Monitor patient for bleeding risks, necrosis and/or gangrene of skin & other tissues, “purple toe syndrome” and drug/herbal interaction.

4. Warfarin dose titration

a. Give warfarin daily at 1800. When applicable, start warfarin within 24 hours of beginning intravenous heparin infusion, LMWH, or fondaparinux and overlap warfarin + heparin/LMWH/fondaparinux for 5 days and until desired INR achieved for 2 consecutive days.

b. Due to half-life of clotting factors affected by warfarin, a desirable INR may not be achieved for 5 to 7 days.

c. If INR rises less than 0.6 increments in 24 hours consider waiting 2 to 3 days to adjust dose to avoid excessive anticoagulation.

d. If INR rises 0.6 to under 0.9 increments in 24 hours, reduce warfarin dose up to 50% of the previous dose to avoid excessive anticoagulation.

e. If INR rises 0.9 and above increment in 24 hours, order a stat INR within 6 to 12 hours after the previous INR before choosing an action.

f. The following chart is provided for guidance and should not replace clinical judgment.

Day

INR

[Designed for INR goal 2.0 – 3.0, For

2.5 – 3.5 use with caution]

Warfarin Adjustment

Day 1 (Baseline) 2.5 to 4mg or 5mg 10mg

Day 2

Under 1.5 2.5 to 4mg or 5mg 7.5 to 10 mg

1.5 to 1.9 2.5mg 2.5mg

2 to 2.5 1 to 2.5mg 1 to 2.5mg

Over 2.5 Hold Dose Hold Dose

Day 3

Under 1.5 5 to 10mg 5 to 10mg

1.5 to 1.9 2.5 to 5mg 2.5 to 5mg

2 to 3 0 to 2.5mg 0 to 2.5mg

Over 3 Hold Dose Hold Dose

Day 4

Under 1.5 10 mg 10 mg

1.5 to 1.9 5 to 7.5 mg 5 to 7.5 mg

2 to 3 [up to 3.5] 0 to 5mg 0 to 5mg

Over 3.5 Hold Dose Hold Dose

Day 5

Under 1.5 10mg 10mg

1.5 to 1.9 7.5 to 10mg 7.5 to 10mg

2 to 3 [up to 3.5] 2.5 to 5mg 2.5 to 7.5mg

Over 3.5 Hold Dose Hold Dose

Day 6

Under 1.5 7.5 to 12.5mg 7.5 to 12.5mg

1.5 to 1.9 5 to 10 mg 5 to 10 mg

2 to 3 [up to 3.5] 2.5 to 5 mg 2.5 to 7.5mg

Over 3.5 Hold Dose Hold Dose

5. Discharge Considerations

a. Recommended warfarin tablet strengths for outpatient warfarin prescriptions are 2mg or 5mg tablets.

b. INR following hospital discharge.

(1) If INR stable – schedule INR within 3-5 days

(2) If INR not stable – schedule INR within 1-3 days

c. Provide warfarin patient education booklet – document education in electronic medical record.

Attachment D

Outpatient Warfarin Initiation Protocol

1. Obtain baseline laboratory values prior to starting warfarin, including:

a. CBC with platelets

b. Prothrombin time (PT)

c. International normalized ratio (INR)

2. Determine Appropriate Starting Dose of Warfarin

a. Consider patient-specific hemorrhagic risks vs. thrombotic risks

b. The key to choosing the initial warfarin dose is evaluating patient factors that may affect warfarin sensitivity and responding appropriately to changes in INR. Select an initial dose that represents the maintenance dose the patient is most likely to require.

c. In patients sufficiently healthy to be treated as outpatients, initiation may begin with 10mg for the first 2 doses with subsequent dosing based on the INR response (Grade 2C). Loading (first) doses of > 10mg of warfarin are Not recommended.

d. A starting routine dose of ≤ 5mg is recommended in some populations (Grade 1C), among which include the following:

(1) Taking medications known to increase sensitivity to warfarin (i.e. amiodarone)

(2) Elderly (age > 60) or patients who are debilitated

(3) Low body weight (< 50kg)

(4) Elevated baseline INR

(5) High risk of bleeding

(6) Recent illness, including diarrhea and/or fever

(7) Recent major surgery

(8) Malnutrition, low albumin, or decreased oral intake (NPO > 3 days)

(9) Malignancy

(10) Congestive heart failure

(11) Renal failure

(12) Liver dysfunction

(13) Hyperthyroidism

Attachment E

e. Younger patients with certain indications (i.e. deep vein thrombosis or pulmonary embolism) and less co-morbidity may receive larger starting routine doses as indicated

3. INR monitoring

a. INR after the initial 2 – 3 doses of warfarin (Grade 2C) – If INR is therapeutic or above desired range after 2 – 3 doses, then consider holding or reducing warfarin dose

b. Repeat INR every 2 – 4 days until a stable dose has been achieved (typically occurs at 10-14 days)

c. Once INR response is consistently stable, frequency of monitoring can be up to 12 weeks rather than every 4 weeks (Grade 2B).

d. If dose adjustments are required, then more frequent monitoring should be repeated until stable dose is achieved.

4. When immediate anticoagulation is needed and patient qualifies for unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), UFH or LMWH should be continued for at least 4-5 days while initiating warfarin and may be discontinued when the INR has been therapeutic on two measurements approximately 24-48 hours apart.

Note: These practice parameters are designed as guidelines and as such are not a substitute for the best professional judgment of physicians or other health professionals taking into consideration the individual circumstances presented by the patient.

Acceptable medical practice may include a variety of responses to a clinical problem

Nomogram for Adjusting Warfarin Therapy Based on Total Weekly Dose*

(This Table Is for Established Warfarin Patients and Should Not Be Used for Warfarin Initiation)

INR Goal

2.0 – 3.0

Recommendation INR Goal

2.5 – 3.5

< 1.4 May add 10 – 20% of total weekly dose today

Consider increase in total weekly dose by 10 – 20%

Return in 1 week

< 2.0

1.5 – 1.9 May add 5 – 10 % of total weekly dose today

Consider increase in total weekly dose by 5 – 10%

Return in 2 weeks

2.1 – 2.4

2.0 – 3.0 No Change

Return in 4 weeks (no longer than 42 days)

2.5 – 3.5

3.1 – 3.9 May subtract 5 – 10% of total weekly dose today (tomorrow if dose already taken today)

(OR) hold today’s dose (tomorrow if dose already taken today)

Consider decrease in total weekly dose by 5 – 10%

Return in 2 weeks

3.6 – 4.6

4.0 – 5.0 Verify INR with Laboratory results if ancillary test being used

May subtract 5 – 10% of total weekly dose today (tomorrow if dose already taken today) (OR) hold 1 – 2 doses

Consider decrease in total weekly dose by 10 – 20%

Return in 1 week

4.7 – 5.2

INR Goal

2.0 – 3.0

Recommendation INR Goal

2.5 – 3.5

> 5.0 Verify INR with Laboratory results if ancillary test being used

Visit with primary care provider

Monitor INR every 1 – 3 days until 3 or less

Consider restarting with total weekly dose decreased by 20

– 50%

Return every 1 – 5 days until controlled

> 5.2

1. If INR is out of range, strong consideration should be given for adjusting the total weekly dose as described in the above chart unless any of the following apply:

a. The INR is within 0.1 of the goal INR

b. The patient missed one or more doses in the past week

c. The patient took one or more extra doses in the past week

d. The patient took an interacting drug that has now been discontinued

e. The patient recently started an interacting drug and the INR is expected to change

f. The patient had a significant change in dietary vitamin K intake (no change in weekly dose if patient plans to return to previous diet – consider change in weekly dose if patient plans to continue with new diet)

g. The INR is being checked before a procedure or warfarin is currently being held

h. The warfarin is being held because of a recent supratherapeutic INR.

i. The warfarin was started or adjusted less than 5 days ago

j. Any other reason based on the clinical judgment of the anticoagulation provider or physician

Note: These practice parameters are designed as guidelines and as such are not a substitute for the best professional judgment of physicians or other health professionals taking into consideration the individual circumstances presented by the patient.

Acceptable medical practice may include a variety of responses to a clinical problem.

Warfarin Dose Adjustment Steps for Established Patients

1. Calculate weekly dose – this should reflect the last 7 days not including the day of INR draw

Examples

a. 7.5mg daily = 7.5 x 7 = 52.5 mg per week

b. 5mg daily except 2.5mg Monday/Wednesday/Friday (MWF) = (5mg x 4) + (2.5mg x 3)

c. = 27.5 mg per week

2. Determine the smallest increment of change that can be made with the tablet strength the patient is currently taking.

Examples

a. 2mg tablet = 1mg increments

b. 5mg tablet = 2.5mg increments

3. Decide how much of a change in warfarin regimen is desired

a. Small dose adjustment is ~ 5 – 10 %

b. Medium dose adjustment is ~ 10 – 15 %

c. Large dose adjustment is ~ 15 – 20 %

d. Aggressive dose adjustment is greater than 25 %

4. Determine if the incremental changes available with the current tablet strength allow for the targeted change. Do this by calculating: Increment of change + weekly dose X 100%

Examples

a. 5mg daily – 35mg per week with 5mg tablets

Smallest increment of change would be 2.5mg

2.5 / 35 = 0.07 x 100 = 7.1 % change (this is a small dose change)

b. A small increase in regimen would be 37.5mg per week (increase 1 day of the week by 2.5mg) – 5mg daily except 7.5mg Wed

Warfarin Dose Adjustment Steps for Established Patients

c. A small decrease in regimen would be 32.5mg per week

(decrease 1 day of the week by 2.5mg) – 5mg daily except 2.5mg Wed

Other Dosing Considerations

a. Recommended warfarin tablet strengths are 2mg and 5mg tablets

b. Patients should be prescribed only one warfarin tablet strength whenever possible

c. Avoid weekly warfarin dose schedules that involve skipped doses (this may result in wide fluctuations in the INR outside the desired target range. A skipped warfarin dose may result in a full point drop in the INR in some patients over a 24-hour period)

d. Avoid alternating doses (i.e. alternate 1mg and 1.5mg every other day) this results in varying weekly doses and can be confusing for patients. Set weekly doses the same from week to week (i.e. 1mg daily except 1.5mg M, W, F)

e. Provide patients with written warfarin dosing instructions at every visit

f. Encourage patients to use a separate small pillbox for warfarin to allow for ease in changing the pillbox to reflect dosing changes and avoid medication errors.

Attachment F

Recommendations for the Management of Supratherapeutic INRs and Bleeding Complications for Patients Receiving Oral Anticoagulation Therapy

This policy provides guidelines for the management of supratherapeutic INRs and bleeding complications in patients receiving oral anticoagulation therapy. It provides recommendations from the most current Antithrombotic and Thrombolytic Therapy:

American College of Chest Physicians Evidenced-Based Clinical Practice Guidelines, 9th edition, 2012.

Condition Intervention

INR between 4.5 and 10

No evidence of bleeding

Lower dose or omit dose(s) depending on INR; monitor more frequently and resume at lower dose when INR therapeutic; if only minimally above therapeutic range or associated with a transient causative factor, dose reduction may not be required (Grade 2B)

Routine use of vitamin K is not recommended (Grade 2B)

INR > 10

No evidence of bleeding

Omit next dose and give vitamin K (1-2.5 mg po), particularly if at increased risk of bleeding (Grade 2C). If more rapid reversal is required because the patient requires urgent surgery, vitamin K (≤ 5.0 mg po) can be given with the expectation that a reduction of the INR will occur in 24h.If the INR is still high, additional vitamin K (1-2 mg po) can be given (Grade 2C).

Evidence of bleeding at any INR

Hold warfarin therapy and give higher dose of vitamin K (2.5-

5.0 mg po) with the expectation that the INR will be reduced substantially in 24 – 48 h (Grade 1B). Monitor more frequently and use additional vitamin K if necessary. Resume therapy at an appropriately adjusted dose when INR is therapeutic.

Rapid reversal for procedure/surgery

Vitamin K (≤ 5 mg po) can be given with the expectation that a reduction of the INR will occur in 24h. If the INR is still high, additional vitamin K (1-2 mg po) can be given (Grade 2C).

Serious bleeding (at any elevation of INR)

(e.g. noncerebral bleeding requiring transfusion)

Hold warfarin therapy and give vitamin K (5-10 mg by slow IV infusion-minimum of 20minutes), supplemented with FFP, PCC, or rVIIa, depending on the urgency of the situation; vitamin K can be repeated q12h (Grade 1C). Four-factor prothrombin complex concentrate is preferred over plasma (Grade 2C)

Life-threatening bleeding

(e.g. intracranial hemorrhage)

Hold warfarin therapy and give FFP, PCC, or rVIIa supplemented with vitamin K (10mg by slow IV infusion), repeated if necessary depending on INR. (Grade 1C). Four-factor prothrombin complex concentrate is preferred over plasma (Grade 2C)

Attachment F

FFP = fresh frozen plasma; rVIIa = recombinant factor VIIa; PCC = prothrombin complex concentrate; Four-factor prothrombin complex = factors II, IV, IX, X, proteins C and S

†If continuing warfarin therapy is indicated after high doses of vitamin K1, then heparin or low-molecular-weight heparin can be given until the effects of vitamin K1 have been reversed, and the patient becomes responsive to warfarin therapy. It should be noted that INR values > 4.5 are less reliable than values in or near the therapeutic range.

Thus, these guidelines represent an approximate guide for high INRs.

Attachment G

Guidelines for Perioperative and Peri-procedure Management of Antithrombotic Therapy

From Antithrombotic and Thrombolytic Therapy: American College of Clinical Pharmacy (ACCP) Evidence Based Clinical Practice Guidelines, 8th edition, 2008

Bridging Anticoagulation for Patients on Warfarin Therapy

1. Should oral anticoagulant therapy be interrupted?

2. Should the patient have perioperative bridging therapy?

3. What dose of bridging therapy should be used – prophylactic vs. treatment dose?

Thromboembolic risk should be used to determine if bridging therapy should be used.

Post-operative bleeding risk should be used to determine how bridging therapy should be used.

Bleeding Risk

(Perioperative)

Thromboembolism Risk

Examples

(These are not all inclusive examples)

Recommendations for Anticoagulant Therapy

Low

Examples: Dermatologic procedures, Diagnostic EGD’s without biopsy, Eye procedures [except blepharoplasty], diagnostic GI procedures without biopsy)

Low to High See below

INR Normalization prior to Symptoms: Not necessary in many circumstances

Pre-Operative

Hold warfarin (optional†): 2-3 days pre-op or

Reduce dose of warfarin by 50% 4-5 days prior to surgery (procedure performed at an INR of 1.3 to 1.5

† - Holding warfarin not recommended if HIGH TE risk.

Bridging: not recommended.

Post-Operative

Restart Warfarin: At full dose following procedure.

Optional: Postoperatively, prophylactic* dose LMWH may be administered for 5 days when needed. (*See Dosing Guide Below)

Bleeding Risk

(Perioperative)

Thromboembolism Risk

Examples

(These are not all inclusive examples)

Recommendations for Anticoagulant Therapy

Moderate to High

Examples:

Abdominal surgery;

Orthopedic surgery;

Thoracic surgery;

Urologic [including TURP, prostatectomy, bladder] procedures

Vascular surgery;

Intracranial; Spinal;

Aortic aneurysm repair;

Peripheral artery bypass; Reconstructive plastic surgery; Major cancer surgery

(For patients undergoing surgery or procedure

Low

Afib: CHADS2 score 0-2 and no prior stroke or TIA

Venous Thromboembolism (VTE):

single VTE occurred > 12 months ago and no other risk factors

Mechanical Heart Valve:

Bileaflet aortic valve prosthesis without Afib and no other risk factors for stroke

INR Normalization prior to Symptoms:

Recommended

Pre-Operative

Hold warfarin: 5 days before procedure.

Bridging: not recommended. If decision to bridge is made, consider prophylactic dose LMWH bridging started 2 days after d/c warfarin. Last Dose of LMWH: Give 24 hour prior to symptoms and use half of the total daily dose. (See Dosing Guide Below)

Post-Operative – when hemostasis secured – individualize

Restart Warfarin: at full dose 12-24 hours after procedure.

Resume Bridging Therapy: 48-72 hours post-op, adequate hemostasis

Recommended Duration Bridging Therapy: 3-5 days post op associated with very high risk of post-OP bleeding, it may be reasonable to NOT administer LMWH after surgery and to simply resume warfarin)

Intermediate or Moderate

Afib: Congestion Heart Failure, Hypertension, Age Diabetes, prior Stroke (CHADS2) score 3-4

VTE: VTE within past 3-12 mo;

Non-severe thrombophilic conditions (e.g., heterozygous factor V Leiden mutation, heterozygous factor II mutation);

Recurrent VTE;

Active cancer (treated within 6 months or palliative)

Mechanical Heart Valve:

Bileaflet aortic valve prosthesis and one of the following: Afib, prior stroke or Transient Ischemic Attack (TIA), hypertension, diabetes, Congestive Heart Failure (CHF), age > 75 yr.

INR Normalization prior to Symptoms:

Recommended

Pre-Operative

Hold Warfarin: 5 days before procedure

Bridging (Recommended): Full dose OR prophylactic LMWH started 2 days after d/c warfarin. Last Dose of LMWH: Give 24 hour prior to symptoms and use half of the total daily dose. (See Dosing Guide Below)

Post-Operative – when hemostasis secured – individualize restart Warfarin: at full dose 12-24 hours after procedure

Resume Bridging Therapy: 48-72 hours post-op, hemostasis secured

Recommended Duration Bridging Therapy: 5-7 days post op

High/Very High Afib: CHADS2 score 5-6;

Recent (within 3 mos.)

stroke or TIA

Rheumatic valvular heart disease

VTE: Recent VTE within past 3 mos.

Severe thrombophilia (e.g., deficiency of protein C, protein S or antithrombin, antiphospholipid antibodies, or multiple abnormalities)

Mechanical Heart Valve:

Any mitral valve prosthesis;

Older (caged-ball or tilting disc) aortic valve prosthesis;

Recent (within 6 mos.)

stroke or TIA

INR Normalization prior to Symptoms:

Recommended

Pre-Operative

Hold warfarin: 5 days before procedure

Bridging (Recommended): Full dose LMWH started 2 days after d/c of warfarin. Last Dose of LMWH:

Give 24 hour prior to symptoms and use half of the total daily dose.

Post-Operative – when hemostasis secured – individualize

Restart Warfarin: at full dose 12-24 hours after procedure

Resume Bridging Therapy: 48-72 hours post op

Recommended Duration Bridging Therapy: 5-7 days post operatively

TE = thromboembolism, VTE = venous thromboembolism (DVT or PE), d/c = discontinue, LMWH = low molecular weight heparin, Afib = atrial fibrillation, symptoms = surgery or procedure, TIA = transient ischemic attack

Perioperative Management of Antiplatelet Therapy When Interruption in Antiplatelet Therapy Is Necessary and Appropriate

CHADS2 TE Risk Factors for Atrial Fibrillation:

Recent CHF = 1

HTN (treated/untreated) = 1

Age > 75 years = 1

DM = 1

Prior CVA/TIA (Stroke) = 2

LMWH Dosing Guide:

Prophylactic LMWH Dose = enoxaparin 30mg subcutaneously q12 hours (or 40mg subcutaneously q24 hours for ortho procedures)

Treatment (FULL) LMWH Dose = enoxaparin 1mg/kg subcutaneously q12 hours up to 150 mg/dose (alternative = enoxaparin 1.5mg/kg subcutaneously q 24 hours)

Renal dose LMWH for CrCl <30mL/min→ for treatment dose 1mg/kg q 24hr and prophylactic dose 30mg q24 hours - Last dose 36 hours prior to symptoms OR consider use of UFH if renal impairment is severe

Time for Reversal of Anticoagulant Effect: Antithrombotic Effect Following Resumption:

1. Warfarin – takes 2-3 days for anticoagulant effect to begin.

2. LMWH – 3-5 h for peak anticoagulant effect.

3. Aspirin – minutes for antiplatelet effect4) Clopidogrel – 3-7 days for peak inhibition of platelet aggregation after start of 75mg maintenance dose.

Medication Elimination Half- Life

Last Dose Prior to Procedure

Unfractionated Heparin

30 – 60 minutes 4 hour (Grade 1C)

LMWH 4 – 5 hours 24 hours (Grade 1C) Use ½ dose for once-daily dose (Grade 1C)

Fondaparinux 17 – 21 hours 4 – 5 days (Not a good option for Pre-procedure anticoagulation)

These practice parameters are designed as guidelines and as such are not a substitute for the best professional judgment of physicians or other health professionals taking into consideration the individual circumstances presented by the patient.

Acceptable medical practice may include a variety of responses to a clinical problem. Anticoagulation therapy should be individualized.

Drug Stop Prior to Procedure Half-life (t½)

Aspirin (ASA) 7 – 10 days 15-20 min (irreversibly inhibits platelets)

Clopidogrel 7 – 10 days 10 hr (irreversibly affects platelets)

Dipyridamole + ASA 7 – 10 days (due to aspirin) 10 hr (aspirin component irreversibly inhibits platelets)

Cilostazol 2 – 3 days 10 hr (reversibly affects platelets)

Prasugrel 7 days 2-15 hrs (irreversibly affects platelets)

Ticagrelor 5 days 7-9 hrs (reversibly affects platelets)

Short t½ non-steroidal anti-inflammatory drugs (NSAID): ibuprofen, indomethacin, diclofenac, ketoprofen

1 day 2 – 6 hrs

Intermediate t½ NSAID or Cyclooxygenase (Cox)-2 inhibitor: naproxen, sulindac, diflunisal, celecoxibb

2 – 3 days 7 – 15 hrs

Long t½ NSAID: piroxicam, Meloxicam, nabumetone 10 days > 20 hrs

Attachment H

Perioperative Management of Antithrombotic Therapy

Summary of Antithrombotic and Thrombolytic Therapy: ACCP Evidence Based Clinical Practice Guidelines, 9th edition, 2012

2.0 Perioperative Management of Patients Who Are Receiving VKAs

2.1 In patients who require temporary interruption of a Vitamin K Antagonists (VKA) before surgery or procedure, recommend:

Stop VKA 5 days before surgery instead of stopping VKAs within a shorter time interval before surgery, to allow adequate time for the INR to normalize (Grade 1C) [warfarin half-life 36-42hr; VKA may need to be stopped more than 5 days prior to surgery in patients with higher INR target ranges and with advanced age]

2.2 In patients who have had temporary interruption of a VKA before surgery or a procedure:

Resume VKAs approximately 12 to 24 hours (the evening of or the next morning) after surgery and when there is adequate hemostasis instead of later resumption of VKA’s (Grade 2C)

2.3 In patients who require temporary interruption of a VKA before surgery or a procedure and whose INR is still elevated (i.e., > 1.5) 1 to 2 days before surgery, recommend:

Administer low-dose (i.e., 1 to 2 mg) oral vit K to normalize the INR (instead of not) (Grade 2C)

Summary of Antithrombotic and Thrombolytic Therapy: ACCP Evidence Based Clinical Practice Guidelines, 9th edition, 2012

2.4 Mechanical heart valve or atrial fibrillation or VTE patients at:

High risk for thromboembolism:

Bridge with therapeutic-dose SC LMWH or IV UFH instead of no bridging during temporary interruption therapy (Grade 2C)

Therapeutic-dose SC LMWH over IV UFH (Grade 2C)

Moderate risk for thromboembolism:

Either bridging or not-bridging approach may be chosen and should be based on an assessment of individual patient and surgery-related factors.

Patients undergoing procedures associated with a low risk for bleeding in whom bridging may be considered include:

1. Pts. w/ mechanical bileaflet aortic valve and additional stroke risk factors comprising prior stroke or systemic embolism or TIA, hypertension, diabetes, CHF, or age > 75 yrs.

2. Pts. w/ a. fib. And a CHADS2 score of 3 or 4 or prior TE during interruption of warfarin.

3. Pts. w/ VTE within the past 3 to 12 months, non-severe thrombophilia, active cancer, and recurrent VTE.

Patients undergoing the following high-bleeding risk procedures in whom no bridging therapy may be considered include:

1. Major cardiac surgery

2. Carotid endarterectomy surgery

Low risk for thromboembolism:

Suggest…