D.25 VANTHCS ANTICOAGULATION POLICY.pdf

DEPARTMENT OF VETERANS AFFAIRS

NORTH TEXAS HEALTH CARE SYSTEM

July 26, 2017 549/119

VANTHCS MEMORANDUM NO. 119-18

ANTICOAGULATION POLICY - INPATIENT and OUTPATIENT

1. PURPOSE:

The purpose of this policy is to establish standardized policy, responsibilities, and procedures at VA North Texas Health Care System (VANTHCS) for the inpatient and outpatient monitoring of patients on anticoagulants: warfarin (Coumadin®), low molecular-weight heparin (LMWH), unfractionated heparin (UFH), direct oral anticoagulants (DOACs), and direct thrombin inhibitors (DTIs). Management of patients on anticoagulants is a complex task requiring appropriate monitoring strategies to help prevent adverse events. A standardized protocol for monitoring patients, with proper communication among physicians, mid-level providers, nurses, and pharmacists, can lead to improved patient outcomes and decreased anticoagulant therapy-associated risks.

2. POLICY:

a. It is VANTHCS Pharmacy System policy to provide a defined anticoagulation management program to individualize patient care and to reduce the likelihood of patient harm associated with the use of anticoagulants.

b. Warfarin is used in the prevention and treatment of thrombus formation in patients with atrial fibrillation (AF), pulmonary embolism (PE), deep vein thrombosis (DVT), heart valve replacement, and other conditions. Due to warfarin’s narrow therapeutic index and delayed pharmacologic effect, along with numerous potential drug interactions, therapy will be individualized to each Veteran and adjusted according to his/her responsiveness, as indicated by the International Normalized Ratio (INR) derived from the prothrombin time (PT).

Age and concurrent disease states will be considered when warfarin therapy is initiated and continued.

c. Intravenous (IV) Unfractionated Heparin (UFH), Low Molecular Weight Heparin (LMWH), and direct thrombin inhibitors are also used initially to treat patients with atrial fibrillation, pulmonary embolism, deep vein thrombosis, acute coronary syndrome (ACS), and other conditions. Patients who are prescribed IV heparin will be monitored with appropriate laboratory studies (i.e., Activated Partial Thromboplastin Time (APTT) , hemoglobin/ hematocrit (Hgb/Hct), and platelet count (PLT)).

D.25 RFP: 36C25722R0015

d. Direct Oral Anticoagulants (DOACs) are a class of oral anticoagulants. As compared to warfarin, DOACs are characterized by rapid onset, fewer drug-drug interactions, unaffected by vitamin K consumption, and marketed as not requiring routine monitoring. DOACs mechanism of action is through direct inhibition of thrombin (dabigatran) or inhibition of factor Xa and prothrombinase activity (rivaroxaban, apixaban, and edoxaban). DOACs have been approved for non-valvular atrial fibrillation for stroke prevention, treatment of DVT or PE, and some have indications for post knee or hip surgery for DVT prophylaxis.

3. PROCEDURES:

a. Refer to VANTHCS Pharmacy Service Policy and Procedure No. ADM-12 Anticoagulation Therapy Management Procedures (ATMP).

(1) ADM-12 is available under pharmacy’s service policy intranet with the following link:

ANTICOAGULATION THERAPY MGMT-PROCEDURES (ATMP)

(2) Attachments on ADM-12 include the following:

(a) Warfarin dosing for patients newly initiated on warfarin

(b) Recommendations on therapeutic INR range for patients on warfarin

(c) Reversal of heparin and LMWH effect with protamine sulfate

(d) Approaches for management of supratherapeutic INR in the Anticoagulation Outpatient Clinic

(e) Peri-operative management of anticoagulation-risk assessment

(f) Peri-operative interruption of direct oral anticoagulants: a suggested management approach

(g) Estimated bleeding risk of some surgical procedures

(h) Guidelines for monitoring full intensity LMWH therapy/ fondaparinux

(i) Overview of US-Labeled guidance for DOACs anticoagulant transitions

b. Inpatients:

https://vaww.visn17.portal.va.gov/NTX/services/pharmacy/Policy%20Links/ADM-12-Anticoag%20Therapy%20Mgmt.docx

(1) Warfarin:

(a) Oral unit dose warfarin will be used. No splitting of tablets will be allowed.

(b) Patients already on warfarin therapy:

Clinical Anticoagulation staff (clinical pharmacy specialists, clinical pharmacy technicians) will alert the inpatient provider if patients missed their clinic appointment because of their inpatient admission. The inpatient provider will place a consult to Anticoagulation Outpatient Clinic upon discharge.

(c) Initiating inpatient warfarin therapy:

Warfarin will be dosed based on published guidelines or current literature (Attachment A). PT/INR will be measured at baseline and at least every other day until a stable therapeutic level is achieved.

(d) Concurrent use of warfarin and therapeutic heparin or LMWH (bridging):

1 Initiation of warfarin therapy when a rapid anticoagulant effect is required: bridging therapy will be overlapped with warfarin per guidelines. UFH or LMWH may then be discontinued once therapeutic INR has been obtained

2 Bridging is the use of short acting subcutaneous or intravenous anticoagulant.

(e) For management of supratherapeutic INR, bleeding complications, and the use of vitamin K for excessive anticoagulation, refer to Attachment A or current guidelines.

(2) Unfractionated Heparin (UFH):

(a) Standard concentration of UFH 40 units/ml (20,000 units/500 ml D5W) will be used for continuous intravenous infusion. Bolus intravenous doses, when needed, will be given using 10,000 unit/ml, 1 ml vials.

(b) Heparin 20,000 units/250 mL (80 units/mL) will be restricted to patients in the Intensive Care Unit (ICU) or 5A-telemetry.

“Concentrated” heparin will be reserved for patients with concerns of volume overload.

(c) Continuous heparin infusion will be administered only via a programmable infusion pump.

(d) IV UFH orders:

1 The physician will be responsible for ordering IV UFH using the heparin order set in CPRS and adjusting or discontinuing UFH treatment as appropriate.

2 IV UFH dosing will be based on the patient’s dosing weight per the Heparin Protocol in CPRS (refer to Attachment B).

3 Inpatient pharmacists will review the IV UFH orders and verify dose calculations and instructions.

4 Nurses will manage, monitor, and document IV UFH infusion and adjustment per the heparin order set.

5 The diagnosis of heparin-induced thrombocytopenia (HIT) will be considered and managed by the physician if HIT is clinically suspected. Characteristics of HIT: platelet count decrease by more than 50% from baseline or decline below 150 K/cu mm, typical onset on day 5-10 of receiving heparin therapy, and or new thrombosis.

(e) Heparin Reversal:

Stop heparin infusion. Urgent reversal of heparin effect will be managed using protamine sulfate as outlined in (refer to Attachment C).

(3) Low Molecular Weight Heparin (LMWH):

(a) Pre-filled syringes will be used for LMWH.

(b) Dosing of LMWH for DVT, PE, and ACS will be based on the patient’s actual body weight and renal function.

(c) The patient and/or caregiver will be educated on self-injection technique by pharmacy or nursing staff prior to discharge on subcutaneous LMWH.

(d) Refer to Attachment H in ADM-12

(4) Direct Oral Anticoagulants (DOACs):

(a) Examples include but not limited to: dabigatran, rivaroxaban, apixaban, and edoxaban.

(b) Baseline labs will be determined by facility, VISN, or VHA Pharmacy Benefits Management such as CBC, serum creatinine, and Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT).Dabigatran will be dispensed in manufacturer’s original unit dose packaging. Dabigatran should not be crushed; contents must remain intact prior to administration.

(c) The patient and/or caregiver will be educated by Anticoagulation Clinical Pharmacy Specialist or medicine staff prior to discharge.

(d) For emergency or life-threatening bleeding requiring immediate reversal in the following DOACs:

1 Dabigatran:

Idarucizumab is a humanized monoclonal antibody fragment specific to dabigatran. Idarucizumab is FDA approved for as a reversal agent for dabigatran in the setting of life-threatening bleeding and emergency surgery or urgent procedures.

2 Oral Anti-Xa agents such as rivaroxaban or apixaban:

Consider use of 4-factor Prothrombin Complex Concentrate (4F-PCC) (off label) as approved by Pharmacy and Therapeutics Committee (P&T) until FDA approved reversal agents available.

(e) For guidance on DOACs anticoagulant transition, refer to Attachment I in ADM-12.

(5) Direct Thrombin Inhibitors (DTI):

(a) Examples include argatroban and bivalirudin.

(b) The physician will be responsible for ordering DTI using the DTI order set in CPRS and adjusting or discontinuing DTI treatment as appropriate.

(c) IV DTI dosing will be based on the patient’s dosing weight per the DTI Protocol in CPRS.

(d) Inpatient pharmacists will review the IV DTI orders and verify dose calculations and instructions.

(e) Nurses will manage, monitor, and document IV DTI infusion and adjustment per the DTI order set.

c. Outpatients:

(1) Initiating outpatient warfarin therapy:

(a) Warfarin therapy prescribed by a VA provider will be monitored and managed exclusively by the VA. All patients who receive warfarin prescriptions from VANTHCS will be managed by VANTHCS, except those as outlined in section 3a,(2). Patients who meet criteria for enrollment will require a consult to the Anticoagulation Outpatient Clinic.

(b) Pharmacy Service will act as a dispensary function for co-practice (“dual care”) prescriptions from non-VA, contracted providers. Non-VA, contracted providers will monitor, will adjust dosing on anticoagulation therapy, and will review on-going safety in those patients.

(c) Patients may choose to have warfarin prescribed by a VA provider and filled by a non-VA pharmacy as long as they agree to be monitored by the VA. The VA provider will enter the medication into the non-VA medication package in CPRS with the correct administration directions and clearly stated indications for use.

(d) All PT/INR testing will be processed through VANTHCS

Pathology and Laboratory Medicine Service for all patients receiving warfarin from the VA pharmacy.

(e) Warfarin dosing will be determined per chest guidelines

(Refer to Attachment A and B in ADM-12). PT/INR will be measured at baseline and at intervals deemed safe until a stable therapeutic level is achieved.

(f) Warfarin prescriptions will be limited to a one month supply with two refills. Prescriptions for warfarin will not mix tablet strengths to achieve a dose (e.g. no combination of 5mg and 2.5mg strengths).

(g) Patients will be provided with written instructions whenever a dose change is made.

(h) Patients on stable treatment will have a PT/INR drawn up to every six weeks (42 days). Patients will have an INR checked more frequently after initiation of treatment and after any dose adjustment (refer to attachment A and D in ADM-12).

(2) Long-term outpatient monitoring of warfarin therapy:

(a) All patients monitored by the Anticoagulation Outpatient Clinic for warfarin will be vested in the Anticoagulation Management Tool (AMT) after review of initial consult.

(b) Patients may be scheduled for laboratory appointment and may leave after phlebotomy if there are confirmed conditions for timely telephone communications between Anticoagulation Outpatient Clinic and patient. Patient lab results will be evaluated and reviewed with the patient or designated caregiver within 48 hours. If INR is considered critical per VANTHCS Memorandum No. 11-14, patient will be contacted in a timely manner, and documentation of those actions will occur within 24 hours of laboratory contacting Anticoagulation Outpatient Clinic.

(3) Management of supratherapeutic INRs and bleeding events will be guided by current guidelines.

(a) Patients with significant/life-threatening bleeding (symptoms of active bleeding and/or unstable hemodynamic status) will be sent to the Emergency Department. Emergency Department provider will deem, if necessary, for patient’s admission.

(b) Supratherapeutic INRs without active bleeding will be managed by the anticoagulation provider or Anticoagulation Outpatient Clinic per recommended guidelines. (Refer to attachment D in ADM-12.)

(4) Peri-procedural management and bridge therapy with LMWH or fondaparinux:

(a) Peri-procedural is defined as the period of time prior to, during, and shortly after an invasive procedure.

(b) The peri-procedural management of anti-coagulation therapy is a complex subject and involves patient’s risk of thrombosis, severity of thrombosis consequences, patient’s risk of bleeding and other comorbidities, and bleeding risk of surgery. Therefore, the peri-proceduralmanagement of anticoagulation therapy is frequently a multi-disciplinary decision that involves the surgeon, primary care provider, peri-procedural medical consultant, and Anticoagulation Clinical Pharmacist Specialists. The Anticoagulation Outpatient Clinic may coordinate the peri-procedural management of anticoagulation, which will be guided in general by published guidelines (Refer to attachments E and G in ADM-12.)

(5) Long-term outpatient management of LMWH or fondaparinux:

Refer to attachment H in ADM-12 for management and details

(6) Direct Oral Anticoagulants (DOACs):

(a) Examples include but not limited to: dabigatran, rivaroxaban, apixaban, and edoxaban.

(b) Baseline labs will be determined by facility, VISN, or VHA Pharmacy Benefits Management (e.g., Complete Blood Count (CBC), serum creatinine, and AST/ALT.

4. RESPONSIBILITIES:

a. Director:

(1) A policy exists that meets all standards identified in Appendix A in VA Directive 1033 to ensure safe management of anticoagulation therapy.

(2) An Anticoagulation Program Manager has been designated to lead the VANTHCS Anticoagulation Management Program and has been provided with appropriate time to fulfill these duties consistent with the complexity of the local anticoagulation program.

(3) Adequate staff and resources are allotted for the Anticoagulation Management Program to include anticoagulation providers, nurses, pharmacy technicians, registered dietitian/nutritionists, program administration, and information technology support, as appropriate. This includes ensuring that anticoagulation providers have adequate anticoagulation support staff to work at the top of their license and to maximize operational efficiency.

(4) The Anticoagulation Management Program has an appropriate staff-to-patient ratio to provide safe and appropriate care as defined in Appendix A of the VA Directive 1033.

(5) Care is coordinated for traveling patients on anticoagulants in accordance with VHA Handbook 1101.11, Coordinated Care Policy for Traveling Veterans, or subsequent policy issue.

b. Chief of Staff (COS):

(1) A physician is identified as Anticoagulation Management Champion, to be actively involved in defined components of the anticoagulation management program. This champion will serve collaboratively with the Pharmacy Anticoagulation Management Champion to advocate for and provide guidance on anticoagulation and thrombosis issues, and support anticoagulation initiatives at the VANTHCS.

(2) Quality Assurance (QA) information for the VANTHCS anticoagulation management program reports is reviewed through the Pharmacy and Therapeutics (P&T) Committee.

(3) Competencies of non-pharmacist anticoagulation providers and clinical staff directly involved in caring for patients receiving anticoagulation therapy must include minimum components outlined in paragraph 4.a.(6) of VHA Directive 1033.

c. Chief, Pharmacy Service:

(1) The contents of this memorandum.

(2) Competencies specific for anticoagulant therapy for clinical pharmacy specialists with a scope of practice in anticoagulation who are involved managing therapy.

d. Pharmacy staff members are responsible for knowing the content of and complying with the procedures associated with anticoagulation therapy management relevant to their practice.

e. The Anticoagulation Clinic Program Manager (ACPM) and/or the Anticoagulant Therapy Program Coordinator (ATPC) is responsible for:

(1) Oversight and ongoing monitoring of the VANTHCS individualized anticoagulant therapy quality assurance plan and reporting results to the Pharmacy and Therapeutics and Patient Safety Committees.

(2) Selection of specialty training program in anticoagulation therapy management for physicians, pharmacists, mid-level providers, and other required staff.

f. The VANTHCS Designated Learning Officer is responsible for assuring initial and ongoing annual training and competency in anticoagulation therapy for appropriate staff involved in anticoagulation therapy (physicians, pharmacists, mid-level providers, nurses, and others) through Talent Management System (TMS) or other venues.

g. The Associate Director for Patient Care Services is responsible for:

(1) Programmable infusion pumps are used for the intravenous administration of heparin and direct thrombin inhibitors.

(2) Competencies specific for anticoagulation therapy management are included in the competency plans for mid-level practitioners and nursing staff.

h. Inpatient Anticoagulation Therapy:

(1) Inpatient physician provider will:

(a) Determine the indication and goals for anticoagulant therapy including target International Normalized Ratio (INR) or a Partial Thromboplastin Time (PTT) ranges and duration of treatment based on risks and benefits of treatment and monitor the effect of treatment on their patients. See Attachment B in ADM-12 for INR goals and duration based on indication.

(b) Be responsible for the overall management of the patient as well as the safety and efficacy of the anticoagulation therapy.

(c) Review the patient’s medical record for any potential contraindications to anticoagulation treatment therapy and evaluate risk to benefits for anticoagulation therapy.

(d) Ensure patients are assessed for risk factors for bleeding on heparin prior to administration including but not limited to:

1 Recent surgery

2 Trauma

3 Invasive procedures

4 Concomitant hemostatic defects

(e) Review the patient’s medical record for any potential contraindications to heparin (history of thrombocytopenia, active major bleeding) use extreme caution when using glycoprotein IIb/IIIa inhibitors or fibrinolytic agents concomitantly.

(f) Initiate orders for anticoagulation treatment therapy:

1 Document initiation of heparin in CPRS using the heparin infusion template titled “Heparin Protocol Note” for titration to therapeutic APTT.

2 Document status of anticoagulation therapy in the progress note daily (e.g., “INR at goal - continue warfarin).

3 Order laboratory tests for monitoring of anticoagulation therapy.

4 Monitor for signs and symptoms of bleeding.

5 Discontinue anticoagulation upon completion of therapy or when the risks outweigh the benefit.

6 Arrange appropriate outpatient follow-up when the patient is discharged on anticoagulation therapy, by placing an Anticoagulation Outpatient Clinic Consult.

(g) Monitor inpatient anticoagulation with appropriate laboratory tests:

1 Initiation of warfarin: baseline CBC with PT/INR within 7 days.

2 Initiation of UFH: baseline CBC, and aPTT with the use of the Heparin Protocol Note.

3 Continuation of warfarin – baseline INR on addmission, then INR at least every other day until INR is stable;

CBC at least every two weeks.

4 Continuation UFH intravenous infusion:

a Repeat APTT 6 hours after initial maintenance infusion and at any dosage change b After two consecutive therapeutic APTT, order APTT at least every 24 hours.

c APTTshould be ordered 6 hours after any dosage change or at next scheduled draw time.

Obtain CBC daily for 3 days, then at least every 3rd day while on heparin protocol (special attention to platelets).

5 LMWH (therapeutic dosing) a Obtain baseline CBC, serum creatinine, and weight.

b Review CBC at least every other day for the first week, then at least bi-weekly for inpatient wards, creatinine at least bi-weekly for inpatient wards.

c Review platelet count daily for 3 days, then at least weekly while on LMWH. For post-surgery patients, obtain platelet count at least every other day for post-op days 4-14 or until LMWH is stopped.

d A decline in platelet count of more than 50% below the baseline value or platelets less than 150 µ/ul should prompt clinical investigation for HIT. If suspected, physician will diagnose and manage.

e Measurement of Anti-Xa levels may be considered once steady state is achieved as per Refer to Attachment H in ADM-12. Anti-Xa levels should be drawn exactly 4 hours after injection. (Refer to attachment H in ADM-12 for guidance) f Adjust dose if body weight changes, unless due to anasarca or large ascites.

6 Direct Oral Anticoagulants (DOACs) such as, but not limited to edoxaban, dabigatran, rivaroxaban, apixaban:

a Obtain baseline CBC, serum creatinine, and liver function panel b Enter inpatient order via current RDR or consult processes.

c Enter consult to Anticoagulation Outpatient Clinic upon discharge using current consult processes

7 Direct Thrombin Inhibitors for treatment of HIT:

If used in the setting of HIT, discontinue all heparin and LWMH orders, including heparin flushes, and communicate to nurse taking care of the patient

(2) Inpatient Pharmacy Service will:

(a) Ensure only oral unit dose products, pre-filled syringes, or pre-mixed infusion bags for anticoagulation medications are dispensed for inpatients when these types of products are available.

(b) Ensure multi-dose heparin products more concentrated than 5,000 units per milliliter are not stocked without the prior approval of Chief of Pharmacy.

(3) Inpatient Clinical Pharmacy Specialists will:

(a) Monitor laboratory results, and screen for potential drug/drug or drug/diet interactions and any other relevant factors that may affect safety and efficacy of a patient’s anticoagulant therapy.

(b) Communicate any recommendations to the physician provider and/or Anticoagulation Outpatient Clinic verbally and/or via a progress note for consulted patients in the Computerized Patient Record System (CPRS) to include:

1 Medications started, discontinued, or changed during inpatient status that interact with warfarin.

2 Adjustment of anticoagulation dose, if indicated.

3 Order and follow-up of appropriate laboratory tests.

(c) Assist with coordinating transition from inpatient to outpatient setting for any anticoagulant treatment-related problems.

(d) Complete CPRS documentation to include a summary of treatment plan, patient education, and follow-up for patients newly initiated on warfarin.

(e) Provide comprehensive education and training for patients newly initiated on anticoagulation (Refer to Attachment D in ADM- 12).

(f) Recommend that the inpatient provider has entered an

Anticoagulation Outpatient Consult for the patient at the time of discharge.

(4) Inpatient Nursing Service Staff:

(a) Utilize BCMA to scan the patient’s identification band and medication barcode on warfarin, heparin, direct thrombin inhibitor, or LMWH dose before administering the medication.

(b) Implement the heparin protocol order set.

(c) Monitor/receive APTT results and adjust heparin dose timely according to the heparin protocol.

(d) Use only programmable infusion pumps for intravenous administration of heparin and verify with a second licensed nurse on heparin infusion rate on the infusion pump following dosage adjustments.

(e) Document any changes in therapy in CPRS using the

Heparin Infusion template titled “Heparin <Nur Heparin Note>” including current infusion rate, current APTT, any additional bolus doses, change or hold in infusion rate, and date/time that next APTT is due.

(f) Monitor for signs and symptoms of bleeding, including bleeding from gums or nose, blood in urine or stool, unusual bruising, etc. Notify the provider if bleeding/bruising is identified.

(g) Educate patient/caregiver on self-administration of LMWH as needed.

(5) Nutrition and Food Service will:

(a) Ensure a formal process to identify inpatients on warfarin therapy

(b) Ensure steady Vitamin K content of foods during meal planning for enteral or parenteral nutrition for patients on warfarin therapy.

(c) Provide an option for low vitamin K diet for ordering physician

(6) Pathology & Laboratory Medicine Service (P&LMS) will:

(a) Collect and report Prothromblin Time/ International Ration (PT/INR) and APTTresults timely.

(b) Comply with VANTHCS Memorandum 11-14, Communicating Test Results to Providers and Patients.

(c) Notify clinical and pharmacy services timely when there is a change in the reagents used to determine the Activated Partial Thrombolastin Time (APTT) and when there is a recalibration of target APTT range that will require modification of heparin protocol and order sets.

i. Outpatient Anticoagulation Therapy:

(1) Primary Care Provider (PCP) will:

(a) Review patient risk factors for any potential contraindications to anticoagulation.

(b) Determine and document the indication for anticoagulant therapy, baseline PT/INR, duration of treatment, and goal INR range based on assessment of benefits and risks; discuss plan and monitoring requirements with patient; and initiate treatment (Refer to Attachment B in ADM-12) for INR goal and duration of treatment based on indication).

Initial warfarin prescriptions must be entered by provider initating warfarin/referring patient to Anticoagulation Outpatient Clinic.

(c) Be responsible for the overall anticoagulation management of the patient. Address risk-benefit ratio of continued anticoagulant therapy at every visit and discontinue treatment when appropriate.

(d) Order baseline laboratory tests for initiation of anticoagulation therapy prior to patient’s enrollment into the Anticoagulation Outpatient Clinic.

Baseline labs (PT/INR) must be obtained within the past 30 days or within 7 days in newly initiated warfarin patients

(e) When prescribing a new outpatient drug that critically interacts with an anticoagulant, prescriber will:

1 Asses drug interaction

2 Adjust anticoagulant dose if needed

3 Order and follow-up any needed laboratory tests, communicate results to Anticoagulation Outpatient Clinic for patients enrolled in the clinic by contacting the clinic directly or requesting a co-signature on a designated note in CPRS.

(2) Pharmacy Service will:

(a) Verify warfarin prescription orders for appropriateness, compliance with restrictions regarding allowable days, and number of refills.

(b) Verify that warfarin orders include the phrase, “Adjust dose as directed by physician or provider for blood thinning. After business hours call 1-888-252-9970 for dosing questions.”

(c) Ensure INR documentation within the past 42 days before outpatient pharmacy service can dispense warfarin. Outpatient pharmacy will contact Anticoagulation Outpatient Clinic or prescriber if INR within the past 42 days in unavailable.

(d) Allow only single strength warfarin prescription for individual patients.

(e) Provide an on-going quality assurance plan in compliance with this policy and report data to the Pharmacy and Therapeutics Committee regularly, and or Veterans Integrated Service Network (VISN). Data collection and monitoring will include, but is not limited to:

1 Proportion of patients with pathologic bleeding events.

2 Proportion of patients with thrombotic events.

3 Patient incidents, close calls, and near misses associated with anticoagulant medications.

4 Time in therapeutic range.

5 Patients on warfarin who have not had an INR in the last 42 days.

(f) Verify that dabigatran orders include the phrase, “with glassful of water for prevention of blood clots. Swallow capsules whole and do not break, chew, or open capsules. Store in original packaging until ready for use. Do not place in pill box.

(g) Verify that rivaroxaban 15 and 20 mg patient instructions include the directions to take, “with a meal for blood thinning.”

(h) Act as a dispensing pharmacy for prescriptions for outpatient anticoagulation prescriptions to non-VA providers who are contracted, such as contracted VA state homes.

(3) Anticoagulation Outpatient Clinic will:

(a) Initiate and follow an individualized anticoagulant management program for each patient. Monitor patients who are consulted to Anticoagulation Outpatient Clinic who meet criteria for enrollment on chronic anticoagulation therapy with the goals of minimizing risks associated with this treatment, improving efficacy of treatment, and detecting potential drug interactions.

1 Inclusion criteria for enrollment in anticoagulation therapy:

a Established outpatients of VANTHCS who are receiving chronic anticoagulation from

VANTHCS.

b Patients monitored by a PCP at VANTHCS or scheduled for an appointment with a PCP at

VANTHCS.

2 Exclusion criteria for enrollment in Anticoagulation Outpatient Clinic:

a Patients whose anticoagulation is provided for and monitored by non-VA, contracted health professionals.

b Patients admitted to hospital, community living center (CLC), nursing home, long-term care facility, spinal cord unit, or non-VA facility.

c Patients managed by CPS in domicillary or Home Based Primary Care (HBPC). These patients will be managed similar to Anticoagulation Outpatient Clinic patients.

d VA providers who chose to monitor patient’s anticoagulation, such as patients receiving dialysis at VA Dallas Medical Center.

e Traveling Veterans who are visiting the facility for a courtesy INR.

(b) Document indication for anticoagulation therapy, goal INR, duration of treatment, warfarin dose, and weekly schedule, use of LMWH and DOACs, symptoms of bleeding or thromboembolism, interim hospitalizations/significant events, adequacy of anticoagulation, new drug interactions, therapeutic plan, and follow-up at each visit.

(c) Order warfarin, DOACs, and LMWH and appropriate laboratory tests as indicated for ongoing treatment.

(d) Coordinate peri-procedural LMWH bridging, as directed by the treatment team.

(e) Assist with coordinating transition from outpatient to inpatient setting for any anticoagulant treatment-related problems.

(f) Provide comprehensive education for all patients enrolled in the Anticoagulation Outpatient Clinic (Refer to Attachment D in

ADM-12).

(g) Review all INRs when results are available on CPRS and decide on warfarin dosing plan no later than 1-2 business days unless INR results become available after normal business hours, 4:30pm to 8am, or weekends then emergency department will be contacted from non-Anticoagulation Clinic staff regarding results and treatment plan (refer to VANTHCS Memorandum 11-14, Communicating Test Results to Providers and Patients).

(h) Generate a report of INR values greater than or equal to 4.5 to identify patients with supratherapeutic INRs. The report will be assessed by a Clinical Pharmacy Specialist in the Anticoagulation Outpatient Clinic before the end of the next business day.

(i) Ensure that the use of ICD10-code for “Long-Term (current) use of anticoagulants” is on the problem list in CPRS for patients on anticoagulant therapy.

(j) Provide verbal and written instructions to patients or patients’ caretakers whenever a change in the warfarin dosage occurs.

(k) Anticoagulation providers in conjunction with primary care provider must perform periodic risk-benefit assessments for all patients receiving anticoagulant therapy and managed in the anticoagulation management program. In high complexity patients, may consider involving patient’s primary care provider, or consulting specialty services for recommendation.

(l) Frequency of testing and clinic visits for new anticoagulation clinic patients:

1 Patients discharged after initiation of anticoagulation will be seen within 3-7 days after discharge.

2 For all new patients requiring major dose adjustment, the frequency of testing as determined by clinical judgement.

or as outlined from published clinical guidance.

3 Initial follow-up for patients newly initiated on warfarin and LMWH should be scheduled within 3 days.

(m) Refer to Attachment D in ADM-12 for frequency of testing and clinic visits for established anticoagulation patients such as patient who have been enrolled in the Anticoagulation Outpatient Clinic for more than1 month.

(4) Non-VA providers prescribing chronic oral anticoagulants will:

(a) Provide anticoagulation management to patient including ordering of labs at non-VA certified laboratory facility.

(b) Provide periodic assessment of continued therapy.

(c) Prescribe patient’s anticoagulation therapy.

(5) Medical Administration Service (MAS) will:

(a) Schedule Anticoagulation Outpatient Clinic and outpatient laboratory phlebotomy appointments in consultation with the provider.

(b) Assist with printing and mailing all communications and notifications as requested by Anticoagulation Outpatient Clinic providers.

(c) Receive and relay telephone calls and messages for Anticoagulation Outpatient Clinic providers.

(6) Pathology & Laboratory Medicine Service (P&LMS) will:

(a) Ensure timely phlebotomy and laboratory test results and communicate critical INR results according to VANTHCS Memorandum No. 11-14 (Communicating Test Results to Providers and Patients).

(b) Ensure the correct ISI value for the lot number of thromboplastin in use is entered into the coagulation testing instrumentation.

(c) Monitor and document quality control to ensure that the entered ISI value remains valid and accurate.

(d) Ensure 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 calculation of the INR. The Geometric Mean PT will be recalculated with each change of Thromboplastin reagent lot number.

(e) Ensure accuracy of results and retrievability of information.

4. REFERENCES:

a. VHA Directive 1033, Anticoagulation Therapy Management, dated July 29, 2015 ;

b. VANTHCS Memorandum No. 11-14 Communicating Test Results to Providers and Patientsdated October 2016

c. Guyatt GH, Akl EA, Crowther M, et al. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):7S-47S.

d. Rivera RA, Nguyen MT, Martinez-Osorio JI, McNeill MF, Ali SK, Mansi IA.

Preoperative medical consultation: maximizing its benefits. American journal of surgery. Nov 2012;204(5):787-797.

e. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. The New England journal of medicine. May 30 2013;368(22):2113-2124.

f. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. Jun 2008;133(6 Suppl):160S- 198S.

5. RESCISSION: VANTHCS Memorandum No. 119-18, dated May 14, 2014.

Kendrick Brown Interim Director

Attachments

Distribution: A

Attachment A

Inpatient Management of Supratherapeutic INRs

INR Action/Recommendation Greater than therapeutic, but <5 with no significant bleeding and or no surgical intervention needed

Lower dose or omit dose, monitor more frequently, and resume at a lower dose when INR therapeutic. If only minimally above therapeutic range, no dose reduction may be required.

≥5 to <9 (No significant bleeding) Omit 1 or 2 doses. Monitoring INR more frequently), and resume warfarin at a lower dose when INR is therapeutic. If patient is at increased risk of bleeding (increased creatinine, h/o GI bleed, age>70, uncontrolled HTN, fall risk, dementia), consider Vitamin K 2.5mg to 5 mg PO. Check INR in 24-48 h to assure response to therapy).

≥9 (No significant bleeding) Notify physician for assistance with therapeutic plan.

Hold warfarin therapy and administer Vitamin K 5mg to 10mg PO or 2 to 4 mg IV with expectation that INR will be reduced substantially in 24 to 48 hours.

Monitor INR more frequently, and administer additional Vitamin K if necessary. Resume warfarin therapy at a lower dose when INR is therapeutic.

Serious bleeding or emergent surgery at any elevation of INR

• Consider sending patient to ICU

• Hold warfarin

• Vitamin K 10 mg slow IV infusion (<1 mg/min) and 4-factor prothrombin complex concentrate (4F-PCC)-Kcentra or FFP

INR Prior to Vit K

2 to <4 4 to 6 >6

Dose (units of Factor IX)/kg (actual body weight)

25 35 50

Max dose (max units of Factor

IX)

2500 3500 5000

• Check INR level in 30 min after 4F-PCC infusion is complete

• Consider FFP if INR did not correct to less than 1.4 with 4F-PCC (Kcentra) and Vitamin K.

Retreat with Vitamin K every 6 to 12 hours as needed.

INR Action/Recommendation Life-threatening bleeding on warfarin or severe warfarin overdose

• Admit to ICU

• Hold warfarin therapy

• Vitamin K 10 mg by slow IV infusion

(1mg/min) and 4F-PCC (Kcentra)

• Check INR level in 30 min after 4F-PCC infusion is complete

• Reassess INR in ≤ 6 to 12 hours

• Consider FFP if INR did not correct to less than 1.4 with 4F-PCC (Kcentra) and Vitamin K.

• May repeat Vitamin K every 6 to 12 hours as needed.

Intracerebral Hemorrhage (ICH) on warfarin

• Hold warfarin

• Vitamin K 10 mg slow IV infusion (<1 mg/min)

• 4000 units of 4F-PCC if INR unavailable

• Check INR level in 30 minutes when 4F-PCC infusion is complete Vitamin K1

• Oral (PO) is the recommended route of administration; has predictable response, safe, and convenient compared to other dosage forms.

o Oral Vitamin K1 is available as 5 mg tablets. May spilt 5 mg, if 2.5 mg dose desired.

o Higher doses of Vitamin K1 (10 mg or greater) may cause warfarin resistance for 7 days or more.

• Intravenously (IV) is the preferred route only in severe bleeding due to its risk for anaphylaxis. It should be given via piggyback (1 mg/min).

• Subcutaneous (SUBQ) is not recommended due to unpredictable absorption.

Kcentra (non-activated four-factor Prothrombin Complex Concentrate (4F-PCC))

• Is a PCC replacement product prepared from United States sourced plasma

• Contains varying amounts of Factor II, VII, IX and X, Protein C and S, and heparin.

• Product potency is defined by Factor IX content. The range of Factor IX units per vial is 400 to 620 units, labeling of exact content printed on each vial. Pharmacy may round to nearest half vial to approximate dose.

• Dosing is based on actual body weight. Maximum dosing weight is 100 kg.

• Vitamin K is administered to maintain Vitamin K-dependent clotting factor levels once the effects of Kcentra have diminished.

References:

1. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy:

antithrombotic therapy and prevention of thrombosis, 9th ed: American College of

Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2012;141:e44s-e88S.

2. Hanley JP. Warfarin reversal. J Clin Pathol 2004;57;1132-1139.

3. Sarode R, Milling TJ, Refaai Ma, et al. Efficacy and safety of a four-factor prothrombin complex concentrate (4F-PCC) in patients on Vitamin K antagonists presenting with major bleeding: a randomized, plasma- controlled, Phase IIIb study. Circulation 2013; 113.

4. Kcentra® [package insert], Kankakee, IL: CSL Behring LLC; 2013.

5. Yanamadala V, Brian P. Walcott, Peter E. Fecci, et al. Reversal of warfarin associated coagulopathy with 4-factor prothrombin complex concentrate in traumatic brain injury and intracranial hemorrhage. J Clinc Neuroscience 2014;21:1881-1884.

Attachment B

Initial and Ongoing Patient and Family Education

Education of the patient and the family and/or care giver must include the importance of follow-up monitoring, compliance issues, dietary (Vitamin K) concerns, and the potential for adverse drug reactions and interactions. This education will include:

(1) Indication for therapy;

(2) Interactions (drug, diet, and disease);

(3) Daily dosage;

(4) The importance of medication adherence;

(5) The management of missed doses;

(6) Signs and symptoms of bleeding and thromboembolic events, and what to do if such an event occurs;

(7) The need to inform other health care providers about long-term anticoagulation therapy;

(8) The need to inform the anticoagulation provider when changes in medications occur or upcoming procedures are expected;

(9) Risks associated with falling;

(10) Proper tablet identification (for warfarin);

(11) Need to inform the anticoagulation provider about acute illness, major changes in diet, or upcoming travel (for warfarin);

(12) The dangers of using medication from different sources (especially for warfarin);

(13) Monitoring requirements (specifically for warfarin); and

(14) Proper medication storage (specifically for dabigatran).

Attachment C

No-Show Policy

A patient who does not report to lab without notifying Anticoagulation Outpatient Clinic is considered as a “No-Show.” Below are standard operating procedures on how the Anticoagulation Outpatient Clinic operates:

1. Make an attempt to contact patient via telephone within 24 business hours of the missed appointment.

a. If unable reach patient via telephone a message with the rescheduled appointment date/time will be left on voicemail/answering machine

2. Letter with the new appointment date/time and clinc information will be mailed when appropriate to patient

After 3 consecutive no-shows documented in CPRS patients will not be rescheduled into the Anticoagulation Outpatient Clinic :

1. A letter will be mailed to the patient informing him/her that Anticoagulation Outpatient Clinic appointment will not be rescheduled unless patient contacts the clinic for re-scheduling or their PCP enters a new consult.

2. Patients will be given a grace period of up to 3 months after last missed appointment to contact the clinic and reschedule a follow up appointment. After the grace period, patients will need to contact their PCP’s for an new Anticoagulation Outpatient Clinic consult to schedule an appointment.

3. Active anticoagulant prescriptions will be placed on hold . if no action is taken during the grace period (3 months ) the prescription for blood thinner may be discontinued.

4. PPCP(or referring physician) will be notified when a patient has missed 3 consecutive appointments and will not be reschedule into theAnticoagulation Outpatient Clinic by placing him/her as a cosigner on the no-show/cancellation note. Confirmation of acknowledgment will be completed by means of an electronic signature to the final no-show note.

5. Patients exempt from no show policy include the following

a. Left ventricular assist devices (LVADs)

b. Mechanical heart valve (MHV)

Attachment D

Copy of Heparin Protocol Pocket Card

Heparin pocket card is applicable to inpatient ward areas where heparin infusion is administered and monitored for therapeutic levels.

Heparin is available in the following dosage forms:

• 10,000 units per vial for bolus

• 20,0000 units/500 mL infusion bag for “Standard/ACS” Infusion

• 20,000 units/250 mL infusion for “Concentrated” Infusion o Concentrated infusion is only available for use in the ICU and 5A- Telemetry unit

Instructions for ordering prescriber include:

(1) Select Notes tab, then select New Note

(2) Select “Heparin Protocol Note”

(3) Select Indication and Dosing Weight Range

HEPARIN CARD

https://vaww.visn17.portal.va.gov/NTX/services/pharmacy/Policy%20Links/119-18%20Heparin%20Card.pdf

Appendix

4F-PCC 4 factor Prothrombin Complex Concentrate ACS Acute coronary syndrome (ACS) ACS Acute coronary syndrome AF Atrial fibrillation APLS Antiphospholipid Syndrome

APTT

Activated Partial Thromboplastin Time

(APTT)

ATPC Anticoagulant Therapy Program Coordinator ATPM Anticoagulation Therapy Program Manager CPRS computerized patient record CPS Clinical Pharmacy Specialist DOACs Direct Oral Anticoagulants DTI Direct Thrombin Inhibitor DVT Deep vein thrombosis

ERCP

Endoscopic Retrograde Cholangiopancretomy

HBPC Home Based Primary Care HIT Heparin Induced Thrombocytopenia INR International Normalized Ratio LMWH Low Molecular Weight Heparin (LMWH):

MI Myocardial infarction P&T Pharmacy and Therapeutics PCP primary care provider PE Pulmonary embolism QA Quality assurance SE Systemic embolism TEE Transesophageal echocardiography UH unfractionated heparin VANTHCS VA North Texas Health Care System VTE Venous thromboembolism