41. Anticoagulation Flashcards

Question

Patients may use the following non-pharmacological method to reduce the risk of venous thromboembolism: A. Increase their intake of green leafy vegetables. B. Perform several reps of 10 deep squats daily, if the physician approves this type of exercise. C. Consume lots of water. D. Use intermittent pneumatic compression devices. E. Consume more olive oil and green tea.

Answer 1

E. Graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices are two non-pharmacologic measures used to prevent venous thromboembolism.

Answer 2

E. Warfarin should be started on the same day as a parenteral anticoagulant (LMWH or UFH) for DVT/PE. The parenteral anticoagulant must be used in a treatment dose, not a prophylactic dose. Heparin: Tx VTE: 80 units/kg IV bolus (max 5000 units) followed by 18 units/kg/hr (max 1000 units/hr) infusion (actual body weight) enoxaparin (Lovenox): use actual body weight for all. Px VTE (30mg SQ Q12H or 40mg SQdaily; CrCl \<30, 30mgSQdaily) Tx VTE and UA/NSTEMI: 1mg/kg SQ Q12H (or 1.5 mg/kg SC Qdaily for VTE inpatient treatment only; CrCl \<30, 1mg/kg SQ daily)

Answer 3

C. Warfarin is generally dosed in the late afternoon or evening. If the INR is taken earlier in the day, the warfarin dose can still be adjusted prior to administration. Or, if the INR is elevated, the warfarin can be held.

Answer 4

B, C, D, E. All four clinical scenarios are appropriate for monitoring LMWH therapy. Monitor in pregnancy, mechanical valves, morbidly obese, and renal impairment.

Answer 5

E. Heparin is administered by IV or SC injection. Heparin is not administered by IM injection due to pain and the risk of hematoma formation. Heparin is not bioavailable via the oral route.

Answer 6

B, C. Phenobarbital is a strong hepatic enzyme inducer and would lower the INR and put the patient at risk for clotting. Warfarin is a substrate of CYP 2C9. Avoid use with tamoxifen. 2C9 inducers: aprepitant, bosentan, carbamazepine, phenobarbital, phenytoin, primidone, rifampin (large decrease in INR), licorice, St. John's Wort. 2C9 inhibitors: amiodarone (decrease warfarin dose by 30-50%), azole antifungals (fluconazole, ketoconazole, voriconazole), capecitabine, etravirine, fluvastatin, fluvoxamine, macrolide antibiotics, metronidazole, tigecycline, TMP/SMX, zafirlukast

Answer 7

B. Rivaroxaban is an oral Factor Xa inhibitor. Oral Factor Xa Inhibitors (no not use in mechanical heart valve) rivaroxaban (Xarelto): Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis, premature discontinuation increases risk of thrombotic events. CI: active major bleeding. Warnings: avoid with moderate-severe hepatic impairment or any degree associated with coagulopathy, avoid use in severe renal impairment (DVT tx/px CrCl \<30; AFib CrCl\<15). SE: bleeding anemia, pregnancy (C). No antidote. Discontinue 24 hours prior to elective surgery. \*Any dose ≥15mg needs to be taken with food\* Non-valvular AFib: CrCl \>50 = 20mg PO daily with evening meal, CrCl 15-50 = 15mg PO daily with evening meal, CrCl \<15 = avoid use Tx VTE: 15mg PO BID with food x 21 days, then 20mg PO daily with food. CrCl \<30 = avoid use Px DVT (after hip/knee replacement): 10mg PO daily without regards to meal. CrCl \<30 = avoid use Reduction in risk of recurrence of DVT/PE: 20mg PO daily with food. CrCl \<30 = avoid use Switching from warfarin to rivaroxaban: start when INR \<3 Switching from UFH/LMWH: start at end of infusion or within 2 hours of next evening LMWH dose Missed doses: take as soon as possible on same day. Do not double up EXCEPT when taking 15mg BID (be sure to take 30mg total daily)

Answer 8

B, D, E. Pradaxa, Xarelto and Eliquis are oral anticoagulant options for this patient that do not require laboratory monitoring for efficacy.

Answer 9

D. The administration of vitamin K intravenously is associated with the risk of anaphylaxis (dyspnea, cardiac arrest, hypotension, shock).

Answer 10

E. Apixaban dosing differs for each indication. It can be taken without regards to food. Discontinuation of therapy without adequate anticoagulation with an alternative agent increases the risk of stroke. apixaban (Eliquis): Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis, premature discontinuation increases risk of thrombotic events. CI: active major bleeding. Warning: use not recommended with prosthetic heart valves or severe hepatic impairment. SE: bleeding, anemia, pregnancy (B). No antidote. Discontinue 48 hours prior to elective surgery with moderate/high bleeding risk or 24 hours prior if low bleeding risk. Non-valvular AFib: 5mg BID, or 2.5mg BID if they have at least 2 of the following: age ≥80 y/o, body weight ≤60kg, or SCr ≥1.5 Tx of VTE: 10mg PO BID x 7 days, then 5mg PO BID Px DVT (after hip/knee replacement): 2.5mg PO BID Reduction in risk of recurrence of DVT/PE: 2.5mg PO BID Switching from warfarin to apixaban: start when INR \<2 Switching from apixaban to anticoagulants other than warfarin: discontinue apixaban and start other anticoagulant at next scheduled dose. Missed dose: take as soon as possible on same day; do not double up

Answer 11

B. Dabigatran (Pradaxa) must be kept in the original container and discarded 4 months after opening the original container. Capsules must be swallowed whole. Oral Direct Thrombin (IIa) Inhibitors: directly inhibits thrombin (Factor IIa). dabigatran (Pradaxa): Prevents more stroke than warfarin and favored in CHEST guidelines. Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis, premature discontinuation increases risk of thrombotic events. CI: major active bleeding, patients with mechanical heart valves. SE: dyspepsia, gastritis-like symptoms, bleeding (including more GI bleeding), pregnancy (C). No antidote. Take whole capsule with full glass of water without regards to food. Once open bottle, use within 4 months. Non-valvular AFib: 150mg BID; 75mg BID if CrCl 15-30 Tx of VTE and reduction in risk of recurrence of VTE: 150mg BID when CrCl \>30; no recommendations when CrCl \<30 Switching from warfarin to dabigatran: start when INR \<2 Swithcing from UFH/LMWH: start at end of UFH infusion or within 2 hours of next LMWH dose Missed dose: take dose if \>6 hours from next dose

Answer 12

C. Both anticoagulants should be continued for a minimum of 5 days and until the INR is ≥ 2 for at least 24 hours. This is a common arena for quality improvement and cost saving in hospitals. Continuing the parenteral anticoagulant longer than needed increases cost, length of stay, and potential for adverse effects.

Answer 13

B. Osteoporosis can occur with long-term use. Women who are pregnant and are using heparin long-term are at risk for decreased bone density. Boxed warning: some products contain benzyl alcohol as preservative, use is CI in neonates and infants. CI: uncontrolled active bleed, severe thrombocytopenia, ICH, history of HIT, hypersensitivity to pork products. Warning: do not give IM due to hematoma risk. SE: bleeding, thrombocytopenia, heparin induced thrombocytopenia, hyperkalemia, osteoporosis, pregnancy (C). Monitoring: heparin is monitored via the aPTT (6 hours after initiation, then every 6 hours until therapeutic range of 1.5-2.5 x patient's baseline aPTT), platelet count, Hgb, Hct, bleeding, thrombocytopenia. Antidote: protamine (1mg will reverse 100units of heparin, max dose 50mg)

Answer 14

B. Continuation of the parenteral anticoagulant should occur for a minimum of 5 days and until the INR is therapeutic (INR at 2.0 or above in this scenario) for at least 24 hours.

Answer 15

D. Hematocrit, hemoglobin, platelets, and aPTT are important laboratory parameters to monitor while a patient is receiving heparin therapy.

Answer 16

C. Heparin "lock-flushes" (HepFlush) are used to keep IV lines open (patent). They are not used for anticoagulation. There have been fatal errors made by choosing the incorrect heparin strength. Using a higher dose to flush a line could cause significant bleeding, including fatal hemorrhage. Many of the dosing errors have occurred in neonates.

Answer 17

D. Lovenox is a low molecular weight heparin (LMWH). LMWHs work by binding to antithrombin which then inhibit clotting factors Xa and IIa. Low Molecular Weight Heparin (LMWHs): works similar to heparin except that the inhibition is much greater for Factor Xa than Factor IIa. Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis. CI: history of HIT, active major bleed, hypersensitivity to pork. SE: bleeding, anemia, increase LFTs, thrombocytopenia, hyperkalemia, injection site reactions (bruising), pregnancy (B). Monitoring (Anti-Xa levels can be used to monitor, but not routine (obtain peak anti-Xa levels 4 hours post dose). Monitor in pregnancy, mechanical valves, morbidly obese, and renal impairment. No real antidote, but protamine can be used. Do not expel air bubble.

Answer 18

C. A serious adverse effect associated with heparin therapy is heparin-induced thrombocytopenia, or HIT. This is a significant drop in platelets caused by an immune response against platelets. Platelets must be monitored during therapy. Heparin-induced Thrombocytopenia (HIT) IgG mediated drug reaction that forms heparin antibodies which binds to platelet factor 4 (PF4) and heparin PF4/heparin complex. This complex binds to Fc receptors on platelets and activates platelets. HIT is defined as a platelet drop of \>50% from baseline, putting patients into a prothrombotic state which could lead to HITT (heparin-induced thrombocytopenia thrombosis). HITT is when clots form in both the venous and arterial side (basically clots can form anywhere vs VTE where clots only found in venous system) HIT treatment: stop all forms of heparin and LMWH (including heparin flushes). Stop warfarin and reverse it. Use a direct thrombin inhibitor such as argatroban. Restart warfarin at a lower dose (5mg or less) and platelets have recovered to at least 150,000/mm³

Answer 19

B. Argatroban is FDA approved for use in HIT and is recommended first-line by the CHEST guidelines. IV Direct Thrombin (IIa) Inhibitors: directly inhibit thrombin (Factor IIa). used in patients with a history of HIT. CI: active major bleed. SE: bleeding, anemia, hematoma, pregnancy (B). No cross reaction with HIT. Not antidote. argatroban: drug of choice in HIT. must be protected from light during administration. decrease dose in hepatic impairment bivalirudin (Angiomax): used in cardiac cath lab. decrease dose when CrCl \<30 Both agents: HIT dosing (initial 2mcg/kg/min, titrate to target aPTT, max 10mcg/kg/min). PCI (IV bolus followed by infusion, all are weight-based)

Answer 20

C. The CHEST guidelines are used for antithrombotics. There are valuable resources on the safe use of antithrombotics on the Institute for Safe Medication Practices at www.ismp.org

Answer 21

B. Fluconazole inhibits the metabolism of warfarin; therefore, increasing the INR and potentially causing the patient to bleed. Warfarin is a substrate of CYP 2C9. Avoid use with tamoxifen. 2C9 inducers: aprepitant, bosentan, carbamazepine, phenobarbital, phenytoin, primidone, rifampin (large decrease in INR), licorice, St. John's Wort. 2C9 inhibitors: amiodarone (decrease warfarin dose by 30-50%), azole antifungals (fluconazole, ketoconazole, voriconazole), capecitabine, etravirine, fluvastatin, fluvoxamine, macrolide antibiotics, metronidazole, tigecycline, TMP/SMX, zafirlukast

Answer 22

A. Pradaxa is an oral direct thrombin (Factor IIa) inhibitor. Direct thrombin inhibitors (which block thrombin, as the name suggests) decrease the amount of fibrin available for clot formation. Oral Direct Thrombin (IIa) Inhibitors: directly inhibits thrombin (Factor IIa). dabigatran (Pradaxa): Prevents more stroke than warfarin and favored in CHEST guidelines. Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis, premature discontinuation increases risk of thrombotic events. CI: major active bleeding, patients with mechanical heart valves. SE: dyspepsia, gastritis-like symptoms, bleeding (including more GI bleeding), pregnancy (C). No antidote. Take whole capsule with full glass of water without regards to food. Once open bottle, use within 4 months.

Answer 23

A, B. The primary risks in this patient from not using anticoagulants or having anticoagulants at subtherapeutic levels are deep vein thrombosis (DVT) and/or pulmonary embolism (PE).

Answer 24

A. NSAIDs, like Advil Migraine, do not raise the INR, but they do increase bleeding risk by an antiplatelet effect. Willow bark can increase the bleeding risk as well. Herbal/Natural Product Drug: Increase bleeding risk (ginkgo biloba, bromelain, danshen, dong quai, vitamin E, evening primrose oil, echinacea, high doses of fish oils, garlic, glucosamine, goldenseal, grapefruit, policosanol, willow bark, wintergreen oil). Decrease effectiveness of warfarin (alfalfa, American ginseng, green tea, coenzyme Q-10, vitamin K, St John's Wort) "Alcohol Can Get Gina Singing" = alfalfa, coenzyme, green tea, ginseng, st. john's.

Answer 25

B, D. Warfarin is a vitamin K antagonist. Vitamin K is required for the carboxylation of clotting factors II, VII, IX, and X. Without adequate vitamin K, the liver produces the factors-but they have reduced coagulant activity.

Answer 26

D. The international normalized ratio (INR) is the test used to measure the effectiveness of warfarin.

Answer 27

C. For patients with atrial fibrillation and CrCl 15-30 mL/min, the recommended dose is 75 mg twice daily. Dabigatran is dosed BID and it is important that patients remember to take both doses. The medication does not last long and if it is not taken appropriately, the patient is at risk of stroke. Dabigatran is taken without regard to meals. dabigatran (Pradaxa): Prevents more stroke than warfarin and favored in CHEST guidelines. Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis, premature discontinuation increases risk of thrombotic events. CI: major active bleeding, patients with mechanical heart valves. SE: dyspepsia, gastritis-like symptoms, bleeding (including more GI bleeding), pregnancy (C). No antidote. Take whole capsule with full glass of water without regards to food. Once open bottle, use within 4 months. Non-valvular AFib: 150mg BID; 75mg BID if CrCl 15-30 Tx of VTE and reduction in risk of recurrence of VTE: 150mg BID when CrCl \>30; no recommendations when CrCl \<30 Switching from warfarin to dabigatran: start when INR \<2 Swithcing from UFH/LMWH: start at end of UFH infusion or within 2 hours of next LMWH dose Missed dose: take dose if \>6 hours from next dose

Answer 28

A. Protamine is the antidote for heparin. Unfractionated Heparin (UFH): binds to antithrombin (AT) and inactivates thrombin (Factor IIa) and Factor Xa (as well as factors IXa, XIa, XIIa, and plasmin) and prevents the conversion of fibrinogen to fibrin. Px VTE: 5000 units SQ Q8-12H Tx VTE: 80 units/kg IV bolus (max 5000 units) followed by 18 units/kg/hr (max 1000 units/hr) infusion (actual body weight) Tx ACS/STEMI: 60 units/kg IV bolus (max 4000 units) followed by 12 units/kg/hr (max 1000 units/hr) infusion (actual body weight) Boxed warning: some products contain benzyl alcohol as preservative, use is CI in neonates and infants. CI: uncontrolled active bleed, severe thrombocytopenia, ICH, history of HIT, hypersensitivity to pork products. Warning: do not give IM due to hematoma risk. SE: bleeding, thrombocytopenia, heparin induced thrombocytopenia, hyperkalemia, osteoporosis, pregnancy (C). Monitoring: heparin is monitored via the aPTT (6 hours after initiation, then every 6 hours until therapeutic range of 1.5-2.5 x patient's baseline aPTT), platelet count, Hgb, Hct, bleeding, thrombocytopenia. Antidote: protamine (1mg will reverse 100units of heparin, max dose 50mg)

Answer 29

A. Treating Supratherapeutic INRs: Antidote is vitamin K: PO or IV only. INR above range, but \<4.5 = reduce or skip dose of warfarin. resume when therapeutic (may need to reduce dose) INR of 4.5-10, without bleeding = PO vitamin K only if high bleeding risk 1-2.5mg. resume warfarin at lower dose INR \>10, without bleeding = PO vitamin K 2.5-5mg. hold warfarin Major bleeding from warfarin (any INR) = IV vitamin K 5-10mg AND four factor prothrombin complex concentrate (PCC) due to less risks. hold warfarin therapy

Answer 30

B. According to the CHEST 2012 guidelines, patients with a supratherapeutic INR of 4.5 - 10 and without bleeding should not routinely receive vitamin K. Therefore, the patient should have 1 - 2 doses of warfarin held and the INR monitored. Restart warfarin at a lower dose when the INR is in the therapeutic range. Treating Supratherapeutic INRs: Antidote is vitamin K: PO or IV only. INR above range, but \<4.5 = reduce or skip dose of warfarin. resume when therapeutic (may need to reduce dose) INR of 4.5-10, without bleeding = PO vitamin K only if high bleeding risk 1-2.5mg. resume warfarin at lower dose INR \>10, without bleeding = PO vitamin K 2.5-5mg. hold warfarin Major bleeding from warfarin (any INR) = IV vitamin K 5-10mg AND four factor prothrombin complex concentrate (PCC) due to less risks. hold warfarin therapy

Answer 31

E. No monitoring of efficacy is required for Xarelto and the dose is correct for PY based on renal function and indication. rivaroxaban (Xarelto): Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis, premature discontinuation increases risk of thrombotic events. CI: active major bleeding. Warnings: avoid with moderate-severe hepatic impairment or any degree associated with coagulopathy, avoid use in severe renal impairment (DVT tx/px CrCl \<30; AFib CrCl\<15). SE: bleeding anemia, pregnancy (C). No antidote. Discontinue 24 hours prior to elective surgery. \*Any dose ≥15mg needs to be taken with food\* Non-valvular AFib: CrCl \>50 = 20mg PO daily with evening meal, CrCl 15-50 = 15mg PO daily with evening meal, CrCl \<15 = avoid use Tx VTE: 15mg PO BID with food x 21 days, then 20mg PO daily with food. CrCl \<30 = avoid use Px DVT (after hip/knee replacement): 10mg PO daily without regards to meal. CrCl \<30 = avoid use Reduction in risk of recurrence of DVT/PE: 20mg PO daily with food. CrCl \<30 = avoid use Switching from warfarin to rivaroxaban: start when INR \<3 Switching from UFH/LMWH: start at end of infusion or within 2 hours of next evening LMWH dose Missed doses: take as soon as possible on same day. Do not double up EXCEPT when taking 15mg BID (be sure to take 30mg total daily)

Answer 32

C. Although the frequency of purple toe syndrome is low, the number of patients receiving warfarin is high. Pharmacists should maintain vigilance when counseling patients who are taking warfarin, especially those with atherosclerotic disease who have highest risk for purple toe syndrome. If present, the patient must report to the physician and warfarin will be discontinued. warfarin (Coumadin, Jantoven): competitively inhibits the C1 subunit of the multi-unit vitamin L epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K epoxide and causing depletion of active clotting factors II, VII, IX and X and protein C/S. Boxed warning: may cause major or fatal bleeding. CI: hemorrhagic tendencies (cerebrovascular hemorrhage, bacterial endocarditis, pericarditis, pericardial effusions), blood dyscrasias, pregnancy (except with mechanical heart valves at high risk for thromboembolism), uncontrolled hypertension, non-compliance, recent or potential surgery of the eye or CNS, major regional lumbar block anesthesia or traumatic surgery resulting in large, open surfaces, (pre-)eclampsia, threatened abortion. SE: bleeding, skin necrosis, purple toe syndrome, pregnancy (X), pregnancy (D) for mechanical heart valve. Monitor: INR target 2.5, range is 2-3 for most (2.5-3.5 for mechanical mitral valve or 2 mechanical heart valves). Antidote is vitamin K. S-enantiomer is 2.7-3.8 times more potent than R-enantiomer. Dosing: Start 10mg daily for first 2 days in healthy outpatient, then adjust dose per INR values. Doses of ≤5mg may be appropriate starting dose for those who are elderly, malnourished, taking drugs which increases warfarin levels, liver disease, heart failure, or have high risk of bleeding.

Answer 33

C. Genetic testing for warfarin is not recommended, according to the CHEST 2012 updated recommendations. A starting dose of 10 mg for the first 2 doses (then adjust per INR value) is appropriate for patients who are healthy enough to begin therapy as outpatients. warfarin (Coumadin, Jantoven): competitively inhibits the C1 subunit of the multi-unit vitamin L epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K epoxide and causing depletion of active clotting factors II, VII, IX and X and protein C/S. Boxed warning: may cause major or fatal bleeding. CI: hemorrhagic tendencies (cerebrovascular hemorrhage, bacterial endocarditis, pericarditis, pericardial effusions), blood dyscrasias, pregnancy (except with mechanical heart valves at high risk for thromboembolism), uncontrolled hypertension, non-compliance, recent or potential surgery of the eye or CNS, major regional lumbar block anesthesia or traumatic surgery resulting in large, open surfaces, (pre-)eclampsia, threatened abortion. SE: bleeding, skin necrosis, purple toe syndrome, pregnancy (X), pregnancy (D) for mechanical heart valve. Monitor: INR target 2.5, range is 2-3 for most (2.5-3.5 for mechanical mitral valve or 2 mechanical heart valves). Antidote is vitamin K. S-enantiomer is 2.7-3.8 times more potent than R-enantiomer. Dosing: Start 10mg daily for first 2 days in healthy outpatient, then adjust dose per INR values. Doses of ≤5mg may be appropriate starting dose for those who are elderly, malnourished, taking drugs which increases warfarin levels, liver disease, heart failure, or have high risk of bleeding.

Answer 34

B. With an INR of 2.8 on Day #3 of therapy, warfarin doses of 0-2.5 mg would adhere to the hospital protocol.

Answer 35

A, B, D. Glucosamine, grapefruit and willow bark (among others) can increase the INR. Alfalfa can decrease the INR. Herbal/Natural Product Drug: Increase bleeding risk (ginkgo biloba, bromelain, danshen, dong quai, vitamin E, evening primrose oil, echinacea, high doses of fish oils, garlic, glucosamine, goldenseal, grapefruit, policosanol, willow bark, wintergreen oil). Decrease effectiveness of warfarin (alfalfa, American ginseng, green tea, coenzyme Q-10, vitamin K, St John's Wort) "Alcohol Can Get Gina Singing" = alfalfa, coenzyme, green tea, ginseng, st. john's.

Answer 36

A. The brand name for apixaban is Eliquis. Xarelto (rivaroxaban) Fragmin (dalteparin) Arixtra (fondaparinux)

Answer 37

E. Warfarin 4 mg comes as a blue tablet. Warfarin colors: 1mg (pink), 2mg (lavender/purple), 2.5mg (Christmas green), 3mg (tan), 4mg (blue), 5mg (peach), 6mg (forest green/teal), 7.5mg (yellow teeth), 10mg (whiten)

Answer 38

B. The brand name of bivalirudin is Angiomax.

Answer 39

B. Sulfamethoxazole/trimethoprim (Bactrim, Septra) impairs the hepatic metabolism of warfarin. It is a strong 2C9 inhibitor, and may also involve displacement of warfarin from protein binding sites or alterations in intestinal flora. This interaction can cause the INR to increase. Warfarin is a substrate of CYP 2C9. Avoid use with tamoxifen. 2C9 inducers: aprepitant, bosentan, carbamazepine, phenobarbital, phenytoin, primidone, rifampin (large decrease in INR), licorice, St. John's Wort. 2C9 inhibitors: amiodarone (decrease warfarin dose by 30-50%), azole antifungals (fluconazole, ketoconazole, voriconazole), capecitabine, etravirine, fluvastatin, fluvoxamine, macrolide antibiotics, metronidazole, tigecycline, TMP/SMX, zafirlukast

Answer 40

D. CHADS2 scoring system is for patients with atrial fibrillation to help guide therapy for the prevention of ischemic strokes.

Answer 41

B, D, E. The doses for warfarin, Pradaxa, and Eliquis are correct for stroke prophylaxis in GH. A renal dosage adjustment would be required for Xarelto. Fondaparinux (Arixtra) is administered via SC injection and is not indicated for stroke prophylaxis in atrial fibrillation. Pradaxa: Non-valvular AFib: 150mg BID; 75mg BID if CrCl 15-30 Eliquis: Non-valvular AFib: 5mg BID, or 2.5mg BID if they have at least 2 of the following: age ≥80 y/o, body weight ≤60kg, or SCr ≥1.5

Answer 42

C. In patients who are receiving bridging anticoagulation with therapeutic dose LMWH therapy and undergoing high-bleeding risk surgery, it is recommended to resume the LMWH therapy 48 to 72 hours after surgery. Perioperative Management of Patients on Warfarin Stop 5 days before major surgery. If moderate-high clotting risk (mechanical valves, AFib), use bridging therapy. Stop therapeutic-dose LMWH therapy 24 hours prior to surgery. Stop UFH 4-6 hours prior to surgery. If undergoing minor surgery (dental, dermatologic, cataract surgery), can continue warfarin (and ASA). If high INR, can give vitamin K (2.5-5mg IV or PO) Resume warfarin 12-24 hours after surgery, when hemostasis is achieved. Bridging therapy can resume LMWH 48-72 hours after surgery in high bleeding risk surgeries or 24 hours after surgery in low bleeding risk.

Answer 43

E. CHADS2 VAS2 CHF - 1 HTN - 1 Age ≥75 - 2 Diabetes - 1 Stroke - 2 Vascular Disease (prior MI, PAD, aortic plaque) - 1 Age 65-74 - 1 Sex (female) - 1

Answer 44

C. Though no monitoring of efficacy is required for rivaroxaban, it can prolong the PT and aPTT. This depends greatly on lab testing procedures and reagents used (which are not standardized for rivaroxaban and other newer agents). These labs merely indicate the “presence” of rivaroxaban. There is little more we can interpret from these labs at this time. The PT/INR may be prolonged from other causes (e.g., liver disease) that should be investigated.

Answer 45

A. Low Molecular Weight Heparin (LMWHs): works similar to heparin except that the inhibition is much greater for Factor Xa than Factor IIa. Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis. CI: history of HIT, active major bleed, hypersensitivity to pork. SE: bleeding, anemia, increase LFTs, thrombocytopenia, hyperkalemia, injection site reactions (bruising), pregnancy (B). Monitoring (Anti-Xa levels can be used to monitor, but not routine (obtain peak anti-Xa levels 4 hours post dose). Monitor in pregnancy, mechanical valves, morbidly obese, and renal impairment. No real antidote, but protamine can be used. Do not expel air bubble. enoxaparin (Lovenox): use actual body weight for all. Px VTE (30mg SQ Q12H or 40mg SQdaily; CrCl \<30, 30mgSQdaily) Tx VTE and UA/NSTEMI: 1mg/kg SQ Q12H (or 1.5 mg/kg SC Qdaily for VTE inpatient treatment only; CrCl \<30, 1mg/kg SQ daily) Tx STEMI: For patients \<75 y/o, 30mg IV bolus + 1mg/kg SQ dose, then 1 mg/kg SQ Q12H (max 100mg for first 2 doses only); if CrCl \<30, 30mg IV bolus + 1mg/kg SQ dose, then 1mg/kg SQ daily. For patients ≥75 y/o, 0.75 mg/kg SQ Q12H (no bolus and max 75mg for first 2 doses only); if CrCl \<30, give 1mg/kg SQ daily. For PCI: give 0.3mg/kg IV bolus if last dose was 8-12 hours before balloon inflation.

Answer 46

C. Patients at high risk for thromboembolism should be bridged with a therapeutic dose of enoxaparin. Perioperative Management of Patients on Warfarin Stop 5 days before major surgery. If moderate-high clotting risk (mechanical valves, AFib), use bridging therapy. Stop therapeutic-dose LMWH therapy 24 hours prior to surgery. Stop UFH 4-6 hours prior to surgery. If undergoing minor surgery (dental, dermatologic, cataract surgery), can continue warfarin (and ASA). If high INR, can give vitamin K (2.5-5mg IV or PO) Resume warfarin 12-24 hours after surgery, when hemostasis is achieved. Bridging therapy can resume LMWH 48-72 hours after surgery in high bleeding risk surgeries or 24 hours after surgery in low bleeding risk.

Answer 47

C. A major 2C9 inhibitor will reduce the metabolism of warfarin, increasing the risk of bleeding. A 2C9 inducer would increase warfarin metabolism, increasing the risk of clotting. Warfarin is a substrate of CYP 2C9. Avoid use with tamoxifen. 2C9 inducers: aprepitant, bosentan, carbamazepine, phenobarbital, phenytoin, primidone, rifampin (large decrease in INR), licorice, St. John's Wort. 2C9 inhibitors: amiodarone (decrease warfarin dose by 30-50%), azole antifungals (fluconazole, ketoconazole, voriconazole), capecitabine, etravirine, fluvastatin, fluvoxamine, macrolide antibiotics, metronidazole, tigecycline, TMP/SMX, zafirlukast

Answer 48

C. As long as the patient is hemodynamically stable with no sign or symptoms of uncontrollable bleeding, the patient should continue to receive LMWH and warfarin therapy as directed for recent DVT treatment. It would be appropriate to educate on local measures to stop bleeding from the leg hematoma or lacerations. Since warfarin is not therapeutic, the Lovenox must be continued.

Answer 49

A, B, C, D. Pradaxa, Coumadin, Apixaban, and Xarelto are all approved for stroke prevention in non-valvular atrial fibrillation.

Answer 50

B. Xarelto is indicated for the treatment of pulmonary embolism.

Answer 51

B. The INR range is 2-3 for cardioversion.

Answer 52

A. Multaq (dronedarone), a P-glycoprotein inhibitor, should not be used with Pradaxa in patients with a CrCl 15-30 mL/min.

Answer 53

B. Warfarin 2.5 mg comes as a green tablet. Warfarin colors: 1mg (pink), 2mg (lavender/purple), 2.5mg (Christmas green), 3mg (tan), 4mg (blue), 5mg (peach), 6mg (forest green/teal), 7.5mg (yellow teeth), 10mg (whiten)

Answer 54

C. Low Molecular Weight Heparin (LMWHs): works similar to heparin except that the inhibition is much greater for Factor Xa than Factor IIa. Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis. CI: history of HIT, active major bleed, hypersensitivity to pork. SE: bleeding, anemia, increase LFTs, thrombocytopenia, hyperkalemia, injection site reactions (bruising), pregnancy (B). Monitoring (Anti-Xa levels can be used to monitor, but not routine (obtain peak anti-Xa levels 4 hours post dose). Monitor in pregnancy, mechanical valves, morbidly obese, and renal impairment. No real antidote, but protamine can be used. Do not expel air bubble. enoxaparin (Lovenox): use actual body weight for all. Px VTE (30mg SQ Q12H or 40mg SQdaily; CrCl \<30, 30mgSQdaily) Tx VTE and UA/NSTEMI: 1mg/kg SQ Q12H (or 1.5 mg/kg SC Qdaily for VTE inpatient treatment only; CrCl \<30, 1mg/kg SQ daily) Tx STEMI: For patients \<75 y/o, 30mg IV bolus + 1mg/kg SQ dose, then 1 mg/kg SQ Q12H (max 100mg for first 2 doses only); if CrCl \<30, 30mg IV bolus + 1mg/kg SQ dose, then 1mg/kg SQ daily. For patients ≥75 y/o, 0.75 mg/kg SQ Q12H (no bolus and max 75mg for first 2 doses only); if CrCl \<30, give 1mg/kg SQ daily. For PCI: give 0.3mg/kg IV bolus if last dose was 8-12 hours before balloon inflation.

Answer 55

C. Patient should continue to monitor for any bleeding or bruising for at least 1 week after discontinuation of warfarin since the effect of warfarin may last for at least a week. Patients should also properly dispose of any remaining warfarin tablets by either grinding up with coffee beans and throwing them out in the trash or disposing of them in an appropriate prescription medication disposer. Do not flush medications, except perhaps for the few indicated by the DEA. Even with these, there are alternative methods for drug disposal. The CHEST guidelines (2012) suggest abrupt discontinuation of therapy rather than a gradual tapering of the dose for discontinuation.

Answer 56

D. Regardless of the duration of atrial fibrillation or the method of cardioversion, 4 weeks of anticoagulation is recommended afterward.

Answer 57

D. CHADS2 CHF - 1 HTN - 1 Age ≥75 - 1 Diabetes - 1 Stroke - 2

Answer 58

C. According to CHEST and ASCO guidelines, LMWH is recommended for treatment of VTE over warfarin therapy for patients with cancer. VTE treatment Provoked: treat for 3 months Unprovoked: low-to-moderate risk (treat longer than 3 months), high bleeding risk (treat for 3 months) 2 unprovoked VTEs: treat long-term

Answer 59

E. Warfarin should be initiated the same day as parenteral therapy.

Answer 60

C. Instruct patients that if they miss a dose, take the dose as soon as possible on the same day. Do not take a double dose the next day to make up for a missed dose.

Answer 61

B, C. The patient is experiencing significant bleeding. Discontinue Lovenox and give protamine which will neutralize ~60% of the anti-Factor Xa activity of Lovenox.

Answer 62

A, B, D. HIT is defined as a \> 50% drop in platelet count from baseline.

Answer 63

A. Swallow the capsules whole; do not break, chew, or crush (the capsules should never be opened). Oral Direct Thrombin (IIa) Inhibitors: directly inhibits thrombin (Factor IIa). dabigatran (Pradaxa): Prevents more stroke than warfarin and favored in CHEST guidelines. Boxed warning: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis, premature discontinuation increases risk of thrombotic events. CI: major active bleeding, patients with mechanical heart valves. SE: dyspepsia, gastritis-like symptoms, bleeding (including more GI bleeding), pregnancy (C). No antidote. Take whole capsule with full glass of water without regards to food. Once open bottle, use within 4 months. Non-valvular AFib: 150mg BID; 75mg BID if CrCl 15-30 Tx of VTE and reduction in risk of recurrence of VTE: 150mg BID when CrCl \>30; no recommendations when CrCl \<30 Switching from warfarin to dabigatran: start when INR \<2 Swithcing from UFH/LMWH: start at end of UFH infusion or within 2 hours of next LMWH dose Missed dose: take dose if \>6 hours from next dose

Answer 64

C. According to the 2012 CHEST guidelines, patients with a mechanical aortic valve should have an INR between 2-3. Monitor: INR target 2.5, range is 2-3 for most (2.5-3.5 for mechanical mitral valve or 2 mechanical heart valves). Antidote is vitamin K. S-enantiomer is 2.7-3.8 times more potent than R-enantiomer.

Answer 65

E. Aspirin or anticoagulation should not be used in this case.

Answer 66

C, D, E. Kcentra should not be used in HIT as it contains heparin in the formulation. Kcentra can cause clotting.

Answer 67

D. With an INR of 1.6 on Day #4 of therapy, a warfarin dose of 5-7.5 mg is appropriate according to the hospital protocol.

Answer 68

D. Avoiding vitamin-K rich foods is not healthy. When vitamin K is avoided completely, the INR is more difficult to manage. Consistency is key. It is especially important not to make sudden, large changes in foods rich in vitamin K.

Answer 69

D. CHADS2 CHF - 1 HTN - 1 Age ≥75 - 1 Diabetes - 1 Stroke - 2

Answer 70

C. The generic name for Xarelto is rivaroxaban. warfarin (Coumadin, Jantoven) dabigatran (Pradaxa) apixaban (Eliquis)

Answer 71

B. Once controlled on a stable dose of warfarin for a reasonable time period, the INR can be monitored at up to a 12 week interval.

Answer 72

A, B, C, D, E. All of the conditions can increase the risk of VTE. Risk factors: Major (surgery, major trauma, immobility, cancer, previous venous thromboembolism, pregnancy, estrogen-containing medications or selective estrogen-receptor modulators, erythropoiesis-stimulating agents), other (venous compression, increasing age, acute medical illness, inflammatory bowel disease, nephrotic syndrome, myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, obesity, central venous catherization, inherited/acquired thrombophilia)

Answer 73

A, C. For stroke prevention in atrial fibrillation with CrCl \< 30 ml/min, enoxaparin 70 mg SC once daily and the heparin bolus and continuous infusion option listed are both correct recommendations for GH.

Answer 74

D. Both ibuprofen (Advil) and magnesium salicylate (Doan's) are non-steroidal anti-inflammatory medications and are not recommended for use with warfarin due to an increased risk of bleeding. Acetaminophen is the analgesic of choice when a patient is on warfarin.

Answer 75

C. INR goal of 2.0-3.0 for at least 3 months. The 2012 CHEST guidelines recommend to treat the first unprovoked VTE for at least 3 months. VTE treatment Provoked: treat for 3 months Unprovoked: low-to-moderate risk (treat longer than 3 months), high bleeding risk (treat for 3 months) 2 unprovoked VTEs: treat long-term

Answer 76

D. Intermittent pneumatic compression devices are recommended for patients with high-bleeding risk. They help keep the blood moving and reduce the risk of clot formation.

Answer 77

C. In patients with STEMI who are less than 75 years old, give enoxaparin 30 mg IV bolus plus a 1 mg/kg SC dose followed by 1 mg/kg SC dose Q12H (max 100 mg for the 1st two doses) in patients with CrCl \> 30 mL/min. enoxaparin (Lovenox): use actual body weight for all. Px VTE (30mg SQ Q12H or 40mg SQdaily; CrCl \<30, 30mgSQdaily) Tx VTE and UA/NSTEMI: 1mg/kg SQ Q12H (or 1.5 mg/kg SC Qdaily for VTE inpatient treatment only; CrCl \<30, 1mg/kg SQ daily) Tx STEMI: For patients \<75 y/o, 30mg IV bolus + 1mg/kg SQ dose, then 1 mg/kg SQ Q12H (max 100mg for first 2 doses only); if CrCl \<30, 30mg IV bolus + 1mg/kg SQ dose, then 1mg/kg SQ daily. For patients ≥75 y/o, 0.75 mg/kg SQ Q12H (no bolus and max 75mg for first 2 doses only); if CrCl \<30, give 1mg/kg SQ daily. For PCI: give 0.3mg/kg IV bolus if last dose was 8-12 hours before balloon inflation.

Answer 78

E. The newer agents should not be used for patients with prosthetic heart valves. Jantoven is used for treating these patients. warfarin (Coumadin, Jantoven) Eliquis (apixaban) Xarelto (rivaroxaban) Pradaxa (dabigatran)

Answer 79

B. When converting patients from warfarin therapy to dabigatran, discontinue warfarin and start dabigatran when the international normalized ratio (INR) is below 2. rivaroxaban (Xarelto): start when INR \<3 dabigatran (Pradaxa): start when INR \<2 apixaban (Eliquis): start when INR \<2

Answer 80

A, B, C, D, Rifampin is an inducer and requires a much higher dose-not lower. Dosing: Start 10mg daily for first 2 days in healthy outpatient, then adjust dose per INR values. Doses of ≤5mg may be appropriate starting dose for those who are elderly, malnourished, taking drugs which increases warfarin levels, liver disease, heart failure, or have high risk of bleeding.

Answer 81

A. Warfarin 5 mg comes as a peach tablet. Warfarin colors: 1mg (pink), 2mg (lavender/purple), 2.5mg (Christmas green), 3mg (tan), 4mg (blue), 5mg (peach), 6mg (forest green/teal), 7.5mg (yellow teeth), 10mg (whiten)

Answer 82

B. This patient is antithrombin deficient; therefore, heparin, LMWHs and fondaparinux will not work.

Answer 83

A, C, E. Rifampin, St. John's Wort and phenytoin (among others) will enhance the metabolism of warfarin leading to a decrease in INR.

Answer 84

B. Goal INR range for patients with a mechanical mitral valve is 2.5 - 3.5. Monitor: INR target 2.5, range is 2-3 for most (2.5-3.5 for mechanical mitral valve or 2 mechanical heart valves). Antidote is vitamin K. S-enantiomer is 2.7-3.8 times more potent than R-enantiomer.