Objective: the Purpose of These Modules Is to Facilitate and Assess New Provider S Knowledge

William W Backus Hospital Anticoagulation Clinic Learning Modules for the New Anticoagulation Care Provider

Objective: The purpose of these modules is to facilitate and assess new provider’s knowledge in managing and monitoring anticoagulation therapies including but not limited to warfarin. Each module must be completed followed by a competency evaluation. Competency assessment will be thru examination, observed patient interviews and testing. The modules, in addition to the training process which will be ongoing, should assist in the completion of the assignments. The references suggested to complete these assignments include Managing Oral Anticoagulation Therapy, Ansell and the CHEST Guidelines, 2008 edition. The references listed below are intended to assist the provider in learning about anticoagulation therapy and management and assessment will not include every topic or chapter.

Module I: VKA Therapy - Ansell, part 2. Chapters 16, 25, 27, 29, 30, 31, 41 - CHEST 2008; 160S - Thrombosis Research 125 (2010) 393–397. Single-dose adjustment versus no adjustment of warfarin in stably anticoagulated patients with an occasional international normalized ratio (INR) out of range - Journal of Thrombosis and Haemostasis, 7: 94–101. Warfarin dose management affects INR control o Provider can formulate appropriate dosing and monitoring regimens for VKA o Provider appropriately communicates plan(s) to patient/caregiver - Competency Assessment for this module should be completed prior to or by the start of day one of training in the anticoagulation clinic.

Module II: Interactions: Drug and Dietary - Ansell, part 2. Chapters 35, 36 - Circulation 2009, 120:1115-1122. Improved Oral Anticoagulation After a Dietary Vitamin K- Guided Strategy : A Randomized Controlled Trial. o Identifies types of drug interactions o Identifies monitoring for drug interactions - Competency Assessment for this module should be completed during the first week of training. Module III: Management of critical values and/or bleeding for VKA - Ansell, part 2. Chapters 32, 33 - CHEST 2008; 257S - Ann Intern Med. 2009;150:293-300. Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin A Randomized Trial. - Bleeding risk tools: HAS-BLED, Hemorr2hages. o Identifies risk factors for bleeding - Competency assessment for this module should be completed during the first week of of training.

Module IV: Disease states for VKA therapy - Ansell, Part 2. Chapters 17, 18, 19, 20, 22 - CHEST 2008; 454S, 546S, 593S, 630S, 670S, 708S, 776S, 815S o Identifying indications for warfarin therapy and INR ranges. o Identify risk factors for thrombosis - Competency Assessment for this module should be completed within 30 days of training.

Module V: Perioperative management and bridging - Ansell, part 2. Chapter 37 - CHEST 2008; 299S - Arterioscler Thromb Vasc Biol. 2010;30:442-448. Periprocedural Anticoagulation Management of Patients With Venous Thromboembolism. o Provider demonstrates ability to implement bridging instructions as per protocol o Provider manages LMWH therapy - Competency Assessment for this module should be completed within 30 days of training. William W Backus Hospital Anticoagulation Clinic Module I: VKA Therapy Competency Assessment for New Anticoagulation Care Provider

Employee Name: ______Date: ______

- Module one to be completed prior to training in the anticoagulation clinic or by the start of day one of training in the anticoagulation clinic.

1) Warfarin works by: a) blocking all the blood clotting factors b) enzymatically converting factors II, VII, X into inactive factors c) blocking the action of vitamin K and prevents phospholipid binding of clotting factors II, VII, IX, X. d) enhancing the effects of protein C and S

2) Which statement about the clotting cascade is correct? a) The extrinsic pathway is activated by tissue factor/VII complex and occurs rapidly. b) The intrinsic pathway occurs more slowly compared to the extrinsic pathway and is started by the activation of Factor XII c) The common pathway is the final pathway in the coagulation cascade and results in the fibrin clot. d) All of the above are true

3) The monitoring of warfarin therapy is based on: a) PT b) antiXa level c) APTT d) INR

4) Which vitamin K dependent clotting factor has the longest t1/2? a) Factor II b) Factor VII c) Factor IX d) Factor X

5) The following is true regarding warfarin pharmacokinetics, except: a) R-warfarin is the more relevant enantiomer regarding drug interactions b) S-warfarin is up to 5 times more potent than R-warfarin c) Warfarin is rapidly and completely absorbed in GI tract e) Warfarin is highly protein bound, up to 99%, mostly by albumin 6) A normal INR for a patient not yet started on warfarin is: a) 1 b) 1.5 c) 1.3 d) 2

7) The best approach to initiating warfarin in a naïve patient is to: a) Initiate all patients at 5mg daily b) Obtain baseline INR and initiate at 10mg daily c) Obtain baseline INR, review patients age and medication profile first d) Order CBC, Chem 7 and PT/INR

8) Following warfarin initiation, the first INR check should be performed: a) after 3 doses b) one week after starting therapy c) after 5 doses d) after 1 dose

9) The following factors increase warfarin sensitivity a) age 50 or greater b) elevated baseline INR c) clinical CHF d) all of the above e) b and c

10) _____ True or False: The anticoagulant effect and antithrombotic effect is the same thing. Explain your answer in the space below.

11) The best time of day to take warfarin is: a) on an empty stomach before breakfast b) with the evening meal c) at bedtime d) anytime of day, 24 hours apart

12) Which if the following is not a contraindication for warfarin therapy? a) Pregnancy b) Major surgery or trauma c) Active bleeding d) Spinal puncture e) Asymptomatic PE 13) JA is a 68 year old female on warfarin for idiopathic DVT which occurred 7 months ago. She has been fairly stable on warfarin 6mg daily, however INR one week ago was 1.9 and today it is 1.7. There is no identifiable reason for the subtherapeutic INR. What is the best management option in this scenario? a) continue current regimen for another week b) increase warfarin ~7% c) increase warfarin ~14% d) increase warfarin ~21%

Evaluated by: ______Date: ______

Actions taken if competency test not completed with 70% or greater: ______

Module I competency test: VKA Therapy Employee Name: ______Date: ______

- Module two to be completed during the first week of training.

1) The more significant drug interactions with warfarin occur because of what? a. Inhibition of CYP 2C9 and S-warfarin metabolism b. Inhibition of CYP 3A4 and S-warfarin metabolism c. Inhibition of CYP 2D6 and R-warfarin metabolism

2) Anitibiotics may affect warfarin sensitivity through which mechanisms: a. Inhibition of warfarin metabolism b. Inhibition of Vit K recycling in the liver c. Decrease Vit K production by enteric flora e. A+B f. All of the above

3) A patient newly started on levothyroxine will likely need… a. A warfarin dose increase. b. A warfarin dose decrease. c. No change.

4) Nafcillin and rifampin are enzyme inducers which: a. Are not likely to effect warfarin b. Are likely to increase the patient’s INR c. Are likely to increase the patient’s resistance to warfarin

5) Which of the following drugs or supplements can enhance the anticoagulant effect of warfarin? a) sulfamethoxasole/trimethoprim b) amiodarone c) ginkgo biloba d) all the above

6) All of the following drugs can inhibit the effects of warfarin except: a) carbamazepine b) griseofulvin c) rifampin d) erythromycin e) sucralfate 7) RF is a 32 yr. old female who is receiving warfarin therapy for a recent DVT. While on therapy, RF developed urinary tract infection. The physician wants to use Septra DS for 10 days and asks your opinion of how to manage RFs warfarin therapy. INR 2.2 today. You respond: a) No dose adjustment is necessary since RFs INR is therapeutic, but recheck INR in 3 days due to possible drug interaction b) 75% dose reduction of warfarin is suggested due to the predictable interaction that will more that likely cause an elevation in the INR. c) 25-50% dose increase of warfarin is suggested due to the predictable interaction that will cause a decrease in therapeutic effect of the warfarin. d) Stop the Coumadin, recheck the INR in 3 days and resume at a lower dose.

8) List five foods which contain a high content of vitamin K. Should patients avoid eating foods containing vitamin K while taking warfarin? If the patient has a garden and tells you he/she is feasting on its bounty, how do you respond?

9) What issue often arises when a patient receives more than an adequate dose of Vitamin K for INR reversal?

10) It’s Thanksgiving and your patient really wants cranberry. He tells you he was told to avoid it. How do you respond?

11) Acute alcohol consumption can affect INR by: a) Decreasing INR due to increased liver metabolism b) Elevate INR due to increased catabolism of vitamin k clotting factors c) Have no affect on INR d) Decreased warfarin metabolism due to cyp enzyme competition between acute alcohol consumption and warfarin.

12) ER is on warfarin for atrial fibrillation. He has been on a stable dose of warfarin. He presents for routine INR check with INR of 2.2 (range 2-3) and states that his cardiologist started amiodarone about 3 days ago. The best approach to this medication addition is: a) there is no drug drug interaction b) reduce the warfarin dose by 25% c) continue current warfarin regimen and have patient return in 1 month d) continue current warfarin regimen and have patient return in 1 week

Module II competency test: Drug and Dietary William W Backus Hospital Anticoagulation Clinic Module III: Management of critical values and/or bleeding for VKA for New Anticoagulation Care Provider

- Module three to be completed during the first week of training

1. Major determinants for anticoagulant related bleeding include: a) anticoagulant intensity b) patient characteristics c) concomitant use of drugs affecting hemostasis d) all of the above e) a & c only

2. The frequency of major bleeding is noted to: a) decrease during the first several months of warfarin therapy b) increase over time c) bleeding risk remains the same over time despite duration of warfarin therapy

3. The most common sites of anticoagulant-related bleeding is/are: a) gastrointestinal b) nasal c) subconjuctival d) genitourinary tract e) a & b f) a & d

4. _____ True or False: The use of oral vitamin K in the outpatient setting is never indicated.

5. The best approach to manage an INR of 4.6 in a patient without bleeding is: a) administer Vitamin K 1.25mg po x 1 dose b) hold warfarin x 1 dose c) hold warfarin x 2 doses d) continue current regimen and increase greens

6. The best approach to manage an INR of 9.1 in a patient without bleeding is: a. Hold warfarin and administer 10mg vitamin k po b. Send patient to emergency room c. Hold warfarin x 1 dose, administer 2.5mg vitamin K po, resume warfarin at usual dose the following day d. Hold warfarin x 1 dose, administer 2.5mg vitamin K po, recheck INR the next day. 7. TD is an 80 year old gentleman who has been on warfarin for chronic atrial fibrillation for 5 years. Monthly INR checks have been stable for the last 6 months. He has required very little adjustment in his Coumadin dose in the last 2 years. You see him in your clinic today and his INR is 8.0. There is no indication of bleeding. His current dose of warfarin is 5 mg every day. What would be your recommendation? When would you have TD recheck his INR and how often thereafter?

8. RW is a 75 year old male that was discharged 5 days ago with a Carpentier Edwards bioprosthetic valve in the aortic position. RW has a history of Type II diabetes, chronic atrial fibrillation, and hypertension. Warfarin was begun on day 1 (10mg every day) and the patient was discharged on Day 7 with a prescription for Coumadin 10mg every day with a follow-up visit in the office in two weeks. The INR history of the patient is as follows:

Day 1 Warfarin Dose INR 1 10mg 1.0 3 10mg 1.8 5 10mg 2.4 7 10mg 3.0

Please answer the following question regarding this case.

A. Would it be reasonable to have the patient wait until the follow-up appointment in two weeks to have the INR checked?

B. Based on your response in question A, what would be your recommendations (s) to dosing and/or followup?

9. In patients with variable INR’s, multiple resources suggest the use of low dose daily vitamin K to assist in stabilizing INR’s. Would you implement this plan and if so, what dose of vitamin K would you use? 10. VL presents to clinic for routine followup. She denies med changes or diet changes. INR is therapeutic at 2.4. During continued conversation, you notice she looks pale. Upon further questioning she said she has been very tired lately for no apparent reason. You ask her about signs of bleeding which she denies, but then mentions stools are darker than usual recently. Select the best response. a) You complete her visit with dosing instructions and followup and tell her to contact her PCP within the next week. b) You tell her not to worry about it since you notice she is still taking iron now c) You encourage her to see her PCP promptly or go to ER due to concern of GI bleed. d) You order an H + H and hold the warfarin.

Module III: Management of critical values and/or bleeding for VKA

Module III: Management of critical values and/or bleeding for VKA William W Backus Hospital Anticoagulation Clinic Module IV: Disease states for VKA Therapy for New Anticoagulation Care Provider

- Module four to be completed within 30 days of training.

1. The following is/are risk factors for developing thrombosis: a) Obesity b) Congestive Heart Failure c) Age >35 d) Orthopedic surgery e) A + B f) A + B + D

2. The following is/are hereditary defects which are associated with the risk of developing thrombosis: a) Factor V Leiden b) Protein C Deficiency c) Prothrombin Gene Mutation G20210a d) all of the above

3. DE is a 60 year old male being referred to your anticoagulation clinic with a diagnosis of new onset atrial fibrillation. DE’s past medical history is significant for hypertension, hypercholesterolemia, rheumatoid arthritis, and type 2 diabetes mellitus. Based on the CHEST guidelines, what duration of warfarin therapy do you recommend for DE? Why? a) 3 months to indefinite, CHADS score of 2 b) Indefinite, CHADS score of 4 c) Indefinite, CHADS score of 2 d) Aspirin therapy preferred over warfarin in this patient e) Cardioversion then warfarin for 1 week

4. PA is a 65 yo female with a recent history of breast cancer (receiving tamoxifen), hypertension (well controlled with a diuretic and ACEI), osteoarthritis (takes ibuprofen PRN) and angina (on Imdur and baby ASA). What are her risk factors for a thrombosis?

5. What signs or symptoms below are suggestive of DVT? a) redness, swelling, discoloration of affected limb b) sudden onset of visual changes c) limb warmth to touch d) all of the above e) A + C 6. The recommended INR range for a patient with acute DVT is: a) 1.5 - 2 b) 2-3 c) 2.5 – 3.5 d) Variable pending patient comorbidities

7. The anticipated duration of warfarin therapy for a patient with acute DVT and Prothrombin Gene 20210a mutation is: a) 3 months b) Indefinite c) 6 months d) 12 months

8. CJ is on warfarin for mechanical mitral valve; INR range 3-3.5. She is admitted for acute CVA. INR on admission is 3.1. What is the recommendation for anticoagulation therapy with warfarin?

a) Continue warfarin at a range of 3-3.5 b) Increase range to 3.5-4 c) Reduce the range to 2-3 due to concern of CVA transition to hemorrhagic stroke d) Stop warfarin and continue LMWH indefinitely

9. Which is the correct description of CHADS2 scoring? a) CHF, hypertension, age >65, DM, prior history of stroke b) Cardiomyopathy, hypertension, age >75, DM, prior history of stroke c) CHF, hypertension, age > 75, DM, prior history of stroke d) CHF, hyperlipidemia, age >75, DM, prior history of stroke

10. Inferior vena cava filter is indicated for: a) A patient with acute TE who is contraindicated for warfarin b) A patient at high risk of recurrent PE c) A patient who has TE event while adequately anticoagulated d) All of the above

11. During acute DVT or PE treatment, when transitioning from heparin or enoxaparin to warfarin, what is the minimum that should take place before the heparin/LMWH is stopped: a) INR >2 b) INR > 2 on 2 consecutive days c) At least 5 days of heparin/LMWH treatment d) All of the above should occur before safely discontinuing heparin/LMWH

12. The correct dose of enoxaparin for acute DVT or PE is: a) 1.5mg/kg sc bid Module IV: Disease states for VKA Therapy b) 40mg sc daily c) 30mg sc bid d) 1.5mg/kg sc daily

13. According to the CHEST guidelines, the recommendation for patients with noncardio-embolic stroke or TIA is: a) Antiplatelet therapy b) Warfarin therapy at a goal INR of 2-3 c) Antiplatelet and warfarin therapy d) Dabigatran

Module IV: Disease states for VKA Therapy

Module III: Management of critical Modulevalues IV:and/or Disease bleeding states for for VKA VKA Therapy William W Backus Hospital Anticoagulation Clinic Module V: Perioperative Management and bridging Competency Assessment for New Anticoagulation Care

- Module five to be completed within 30 days of training in the anticoagulation clinic.

1) MS presents to the clinic stating his orthopedic doctor instructed him to hold warfarin 7 days prior to his scheduled TKR. MS is on warfarin for atrial fibrillation. The most appropriate response it: a) Implement said plan b) Review the patient’s diagnosis and implement said plan if appropriate c) Coordinate warfarin interruption with patient’s cardiologist d) Coordinate warfarin interruption with clinic medical director

2) The most likely patient to require LMWH during warfarin interruption is: a) a patient with VTE 4 months ago b) a patient with atrial fibrillation and CHADS2 score of 1 c) a patient with VTE 10 months ago with a history of Factor V Leiden d) b + c e) a + c

3) Warfarin must be interrupted for: a) single dental extractions b) local skin excisions c) epidural injection d) cataract surgery

4) If a patient needs enoxaparin, what labs are necessary prior to implementation: a) H + H b) Platelet count c) serum creatinine d) INR e) all of the above f) b + c + d

5) ____ True or False: Routine antiXa monitoring is necessary during the perioperative period in patients on enoxaparin. 6) Enoxaparin treatment doses are: a. based on ideal body weight when > 80kg b. based on actual body weight and capped at 150kg c. based on actual body weight and not capped

7) Risk of HIT reaction to enoxaparin is about: a) 10% b) 5% c) 1% d) not an adverse clinical event

8) For perioperative bridging therapy using full treatment doses, the last enoxaparin dose given surgery should be: a) 50% of the usual dose on the day before surgery b) full dose, 24 hours prior to surgery c) held for 48 hours prior to surgery

9) When transitioning from heparin or enoxaparin to warfarin during DVT treatment, what is the minimum that should take place before the heparin/enoxaparin is stopped (this is also a key concept during perioperative management): a) INR > 2 b) INR > 2 on 2 consecutive days c) At least 5 days of heparin/enoxaparin treatment d) All of the above should occur before safely discontinuing heparin/enoxaparin

10) Why is fondaparinux not a good agent to use preoperatively?

11) CL is a 55 year old male on warfarin for new onset atrial fibrillation with recent cardioversion to NSR. The cardiologist orders the warfarin at 5mg daily x 3 dose, 7.5mg x 3 dose and lovenox 1mg/kg sc bid until INR is therapeutic x 1 day. The goal INR range is 2-3. Select the best answer regarding this case. a) After 6 doses of warfarin INR is 1.7, you continue lovenox, order warfarin 5mg daily and have CL return to clinic in 2 days b) After 6 doses of warfarin INR is 1.7, you continue lovenox, order warfarin 7.5mg x 1 dose and have CL return to clinic in 1 day c) After 6 doses of warfarin, INR is 1.7, you continue lovenox, order warfarin 12.5mg x dose, and have CL return to clinic in 1 day. d) Discontinue the lovenox as it is close enough and bridge has occurred for several days and order warfarin 5mg daily alternating with 7.5mg daily.

Module V competency test: Perioperative management and bridging 12) Procedures associated with a high bleeding risk include: a) Orthopedic procedures b) Mole removal c) Procedures > 1 hour in duration d) Bladder biopsy e) a + b + d f) a + c + d

13) CS is on enoxaparin bridge for colonoscopy, high TE risk, low bleed risk. She takes warfarin 5mg daily. What is the post procedure plan according to the clinic protocol and best monitoring scenario? a) resume lovenox 24 hours after procedure, start warfarin the night of the procedure at 5mg daily, with the first INR check in 4 days b) resume lovenox 24 hours after procedure, start warfarin the night of the procedure at 7.5mg daily, with the first INR check in 4 days c) resume lovenox the night of the procedure, start warfarin the night of the procedure at 5mg daily, with the first INR check in 4 days d) resume lovenox the night of the procedure, start warfarin the night of the procedure at 7.5mg daily, with the first INR check in 4 days

14) KS will be on lovenox bridge for upcoming TKR, her weight is 154lbs, what is her calculated dose of lovenox if her TE risk is intermediate? a) 105mg b) 100mg c) 110mg d) 120mg

*** By the end of the first month, the provider will be expected to process a bridging order from start to finish identifying any labs, dose calculations, and proper instructions for bridging***

Module V competency test: Perioperative management and bridging