Anticoagulation

AG is beginning warfarin therapy and she asks the pharmacist which foods are high in vitamin K. Which of the following foods are high in vitamin K? (Select ALL that apply.)

A. Spinach B. Cabbage C. Broccoli F. Liver It is important to counsel the patient to eat consistent amounts of vitamin K daily and avoid large, sudden changes in intake of foods rich in vitamin K. These foods should not be eliminated from the diet, but consistency is very important.

(same as above) While attempting to manage GH's heart failure with diuretics, his renal function worsened. His BUN and SCr have increased to 36 and 2.1 respectively. GH's physician feels it would be safest to start an unfractionated heparin drip until the renal function stabilizes. He orders a heparin bolus, followed by 18 units/kg/hour continuous infusion. The hospital uses premixed heparin drips that are 25,000 units/250 mL. How many milliliters of heparin will the patient require per hour? (Answer must be numeric; no units or commas; include a leading zero when the answer is less than 1; round the final answer to the nearest TENTH.)

12.4 Heparin is a very old drug and is used off-label much of the time. In most hospitals, the standard VTE/PE dosing is used for all indications requiring systemic anticoagulation, except STEMI. Actual body weight is used for dosing UFH. 18 units/kg/hr x 69.09 kg = 1243.6364 units/hr x 250 mL/25,000 units = 12.436 mL/hr (round to 12.4 as specified in the question). Refer to Flow Rates - Calculation IV for additional examples.

CD is a 42-year-old male with type 2 diabetes, hypertension and high cholesterol. He did not practice proper foot care and developed an infected big toe. Unfortunately, the infection spread into the bone and he was admitted to the hospital and had his toe amputated. While resting in bed after the surgery, CD developed a deep vein thrombosis. His creatinine clearance is estimated at 55 mL/min and his weight is 80 kg. The physician orders enoxaparin 80 mg SC BID for DVT treatment. Choose the correct statement:

A. The dose is correct as ordered. The ordered dose is correct based on the patient's weight and renal function.

What is the purpose of using a heparin "lock-flush," such as HepFlush?

C. To keep IV lines open 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.

A 58-year-old male comes to the emergency department due to weakness, bleeding gums, and bright red blood in the stool. The patient has been using warfarin for two years and is normally therapeutic, but he reports that his home medication regimen was recently changed. Past Medical History: atrial fibrillation, depression, dyslipidemia, hypertension Allergies: no known drug allergies Home Medications:Amiodarone 200 mg PO BIDCitalopram 20 mg PO dailyLisinopril 10 mg PO dailyMetoprolol 25 mg PO BIDRosuvastatin 20 mg PO HSWarfarin 7.5 mg PO daily Vital Signs: BP 92/49 mmHg, HR 110 bpm, RR 18 bpm, O2 sat 90% on room air, Ht 72", Wt 180 lbs Laboratory Tests:White blood cells 9,500 cells/mm3Hemoglobin 8.4 g/dLHematocrit 25.2%Platelets 100,000/mm3Sodium 144 mEq/LPotassium 4.5 mEq/LChloride 107 mEq/LBicarbonate 23 mEq/LBlood urea nitrogen 18 mg/dLSerum creatinine 1.2 mg/dLGlucose 100 mg/dLINR 9.5 In addition to holding warfarin, which of the following is most appropriate to administer?

A. 4-factor prothrombin complex concentrate and phytonadione 10 mg IV This patient is hemodynamically unstable (hypotension, tachycardia) with a rectal bleed and a low hemoglobin/hematocrit, indicating life-threatening bleeding. Life-threatening bleeding from warfarin [vitamin K epoxide reductase enzyme complex (VKORC1) inhibitor] can occur anywhere in the body (eg, brain, gastrointestinal tract, peritoneal cavity). The following actions must occur when there is serious or life-threatening bleeding from warfarin (regardless of INR): Hold warfarin doses Administer phytonadione (synthetic vitamin K) 10 mg IV and 4-factor prothrombin complex concentrate (PCC) Provide supportive care (eg, supplemental oxygen, fluids, vasopressors) (Choices B and E) Neither PCC nor phytonadione is sufficient as monotherapy to reverse warfarin. PCC rapidly normalizes the INR (within minutes) by providing exogenous clotting factors, but the effect is transient (~8-12 hours). In comparison, phytonadione takes over 12 hours to impact vitamin K-dependent clotting factors, but the effect is longer lasting (days). (Choices C and D) Fresh frozen plasma (FFP) can be given for warfarin reversal when PCC is unavailable. Compared to PCC, FFP takes longer to prepare and requires a larger fluid volume. The correct dose of phytonadione to give with FFP is 10 mg IV, not 2.5 mg PO. Things to remember:Life-threatening bleeding from warfarin should be reversed with 4-factor prothrombin complex concentrate (PCC) and phytonadione 10 mg IV. If PCC is unavailable, fresh frozen plasma can be given.

A hospital's anticoagulation monitoring protocol requires anti-Xa monitoring in patients expected to have altered enoxaparin pharmacokinetics. Which of the following patients receiving enoxaparin will require anti-Xa level monitoring? (Select ALL that apply)

A. A 23-year-old male with a BMI of 40 B. A 35-year-old female at 30 weeks of gestation C. A 45-year-old male with a baseline creatinine clearance of 35mL/min E. A 60-year0old female with a BMI of 18 Enoxaparin (Lovenox), a low molecular weight heparin, potentiates the anticoagulant effects of antithrombin by increasing the ability to inactivate factor Xa. Enoxaparin does not require routine monitoring due to its predictable pharmacokinetic profile in most patients. Select patients with altered enoxaparin pharmacokinetics can develop supratherapeutic or subtherapeutic anti-Xa levels, resulting in bleeding or inadequate anticoagulation. Peak anti-Xa level monitoring (4-6 hours after a SQ dose) can be used to maximize safety and efficacy (eg, adjust enoxaparin dose) when variable pharmacokinetics are a concern. Commonly monitored patient groups include those with any of the following: Extremes of body weight: Patients with low and high body weight are underrepresented in clinical trials. Changes in volume of distribution and renal clearance of enoxaparin lead to increases in anti-Xa activity (increased bleeding risk) with low body weight and decreases in anti-Xa activity (inadequate anticoagulation) with high body weight (Choices A and E). Pregnancy: Renal clearance and volume of distribution of enoxaparin increase as pregnancy progresses, leading to decreased anti-Xa activity (Choice B). Reduced kidney function: Enoxaparin is renally eliminated and accumulates in patients with poor kidney function, leading to increases in anti-Xa activity (Choice C). (Choice D) Rifampin is a strong inducer of CYP450 3A4 and 2C19 and a moderate inducer of 2B6, 2C8, and 2C9. Enoxaparin does not undergo CYP450 metabolism and therefore is not impacted by rifampin. Things to remember:Enoxaparin (Lovenox) has a predictable anticoagulant response in most patients. Patients with variable enoxaparin pharmacokinetics (eg, low or high body weight, pregnancy, poor kidney function) may experience inadequate anticoagulation (low anti-Xa activity) or bleeding (high anti-Xa activity) and may benefit from anti-Xa level monitoring.

A 32-year-old female was admitted to the inpatient cardiac unit on February 3 following an aortic valve replacement. She was started on warfarin 10 mg PO daily and an unfractionated heparin infusion (titrated per hospital protocol) the same day. Laboratory Tests: 2/32/42/52/62/72/8INR0.911.41.722.1Platelets(cells/mm3)205,000182,000150,000146,000108,00078,000 Heparin-induced thrombocytopenia is suspected. Which of the following steps should be taken in the treatment of this patient? (Select ALL that apply)

A. Administer argatroban C. Administer vitamin K D. Discontinue heparin E. Discontinue warfarin Heparin-induced thrombocytopenia (HIT) is suspected in this patient based on the > 50% decrease in platelets within 5-10 days of heparin exposure. HIT, an antibody-mediated complication, occurs when heparin forms complexes with platelet factor 4 (PF4) and IgG, which then attaches to platelets. Mild to moderate thrombocytopenia (rarely < 20,000 cells/mm3) occurs when the spleen removes the platelets with the heparin-PF4-IgG complex. The heparin-PF4-IgG complex also causes platelet activation and a paradoxical prothrombotic state. The 4 Ts score (thrombocytopenia, timing, thrombosis, and other causes) is calculated to assess the probability of HIT. Laboratory tests [eg, enzyme-linked immunosorbent assay (ELISA), serotonin release assays] confirm HIT diagnosis. If HIT is suspected, the following treatment must occur: Discontinue all forms of heparin (unfractionated heparin, low molecular weight heparin) immediately to remove the precipitating factor (Choice D). Discontinue warfarin and reverse with vitamin K to reduce the risk of initial procoagulant effect with warfarin without heparin bridge. Case reports of an undiagnosed deep vein thrombosis (DVT) progressing to venous limb gangrene (severe DVT) have occurred in patients with underlying protein C deficiency and others. Warfarin can be resumed when platelets are > 150,000 cells/mm3 (Choices C and E). Initiate an alternate, rapidly acting anticoagulant to prevent thrombosis. Parenteral treatment options include direct thrombin inhibitors (eg, argatroban, bivalirudin) and fondaparinux (Choice A). (Choice B) Despite the low platelets observed with HIT, there is minimal bleeding risk. Administering platelets may increase the risk of thrombosis by providing more platelets to be activated by the heparin-PF4-IgG complexes. Things to remember:Heparin-induced thrombocytopenia, an antibody-mediated complication, causes low platelets and increases the risk of clotting. Treatment includes discontinuing all forms of heparin and warfarin, giving vitamin K to reverse warfarin, and initiating an alternative non-heparin anticoagulant.

A new patient is using enoxaparin therapy for "bridging" until her INR is therapeutic. She brings the following over-the-counter medicines to the pharmacy window for payment: DHEA, Women's 50+ multivitamin, Advil Migraine, coenzyme Q10 and a B-Complex vitamin. The pharmacist should offer the following advice:

A. Advil Migraine is not safe to use with warfarin; acetaminophen is safer NSAIDs, like Advil Migraine, do not raise the INR, but they do increase bleeding risk by an antiplatelet effect. Willow bark contains plant salicylates and can increase the bleeding risk as well.

KL is a 78-year-old female brought to the emergency department after slipping on ice and hitting her head. Her spouse reports that she took all her home medications 6 hours ago. Past Medical History: atrial fibrillation, generalized anxiety disorder, hypertension, major depressive disorder, osteoporosis Home Medications:Alendronate 70 mg PO weeklyApixaban 5 mg PO twice dailyMultivitamin 1 tablet PO dailyCardizem CD 120 mg PO dailySertraline 100 mg dailyXanax 0.5 mg TID PRN Vital Signs: BP 136/76 mmHg, HR 88 bpm, RR 12 bpm, Pain 9 out of 10 (headache) Diagnostic Tests:CT scan of the head: acute subdural hematoma Prior to hematoma evacuation in the operating room, which of the following medications should KL receive to achieve hemostasis?

A. Andexanet alfa This patient has a subdural hematoma and is going to the operating room to have the cause of the bleed surgically repaired. She should be treated with an anticoagulation reversal agent to stop any additional bleeding or hematoma expansion. Reversal agents for anticoagulants are reserved for treating life-threatening bleeds (eg, intracranial hemorrhage) due to the risk of thrombosis once anticoagulation has been reversed. Andexanet alfa (Andexxa) is a modified, inactive form of factor Xa used to achieve hemostasis by binding to apixaban and rivaroxaban (factor Xa inhibitors). It restores intravascular coagulation by increasing the availability of endogenous factor Xa, which converts prothrombin to thrombin and generates fibrin clots. (Choice B) Flumazenil is the reversal agent for benzodiazepines. Although this patient is on a benzodiazepine (alprazolam), she does not exhibit any signs or symptoms of benzodiazepine overdose that would require reversal. (Choice C) Idarucizumab (Praxbind) is a humanized monoclonal antibody fragment that binds to dabigatran (oral direct thrombin inhibitor) with high affinity and rapidly reverses the anticoagulant effects. (Choice D) Protamine is the reversal agent for unfractionated heparin and low molecular weight heparins (eg, enoxaparin), not apixaban. (Choice E) A reversal agent is indicated because the patient is adherent to her anticoagulation regimen (last dose taken 6 hours ago) and has a life-threatening bleed (subdural hematoma). The factor Xa inhibitor dose and time since last taken will determine the dose of andexanet alfa needed for reversal. Things to remember:Andexanet alfa is administered to reverse the anticoagulation effect in patients who have a life-threatening bleed while taking the factor Xa inhibitors apixaban and rivaroxaban.

DS is a 26-year-old female (5′ 3″, 186 lbs) who comes to the emergency department due to severe pain and swelling in her left calf. For the past month, the patient has been studying for 12 hours per day for an important examination. A left lower extremity ultrasound reveals a deep vein thrombosis. Her laboratory test results are unremarkable, and she has no known drug allergies. The prescriber wishes to treat her deep vein thrombosis with an oral medication that requires no routine monitoring for efficacy. Which of the following medications could the pharmacist recommend? (Select ALL that apply)

A. Apixaban C. Dabigatran Vascular injury, prothrombotic conditions, and blood stasis (ie, Virchow triad) contribute to the activation of the clotting cascade and eventual formation of a venous thromboembolism (VTE). This patient likely developed a deep vein thrombosis (DVT) from blood stasis due to prolonged immobility and obesity (eg, BMI ≥ 30). Patients with a newly diagnosed DVT should be anticoagulated [eg, direct-acting oral anticoagulants (DOACs), warfarin, heparins] for a minimum of 3 months to reduce the risk of recurrent thrombosis and to prevent progression to pulmonary embolism. DOACs [eg, apixaban (Eliquis), rivaroxaban (Xarelto), dabigatran (Pradaxa)] are preferred for treatment of DVT due to their ease of administration (oral), reduced need for routine laboratory monitoring, and superior safety with comparable efficacy when compared to treatment with warfarin. (Choice B) Antiplatelet medications (eg, aspirin) are insufficient for treatment of DVT and are not recommended in any patient groups. (Choices D and E) Both enoxaparin [low molecular weight heparin (LMWH)] and fondaparinux (factor Xa inhibitor) are effective treatments for DVT but are administered subcutaneously. (Choice F) Warfarin, a vitamin K antagonist, remains an option for treating DVT but requires frequent laboratory monitoring for safety and efficacy and initial overlap with an injectable anticoagulant (eg, LMWH). Things to remember:Direct-acting oral anticoagulants are the preferred treatment for deep vein thrombosis. Routine laboratory monitoring of the direct-acting oral anticoagulants is not required for safe and effective use.

The pharmacist will counsel a patient on the correct self-administration technique for enoxaparin. Which of the following are correct counseling statements? (Select ALL that apply.)

A. This medication can cause the patient to bruise and/or bleed more easily B. Choose an area on the right or left side of the patient's abdomen, but not within two inches from the belly button. C. Do not expel the air bubble in the syringe prior to injection. Do not expel the air bubble in the syringe as it can cause the patient to get a subtherapeutic dose because some of the medicine will be lost (as long as the exact dose needed is the amount in the syringe). With some medications, it is recommended to rub the site after injection, but not with drugs that can cause bleeding, such as this one.

A 75-year-old male has been in a rehabilitation center for 8 days following hospitalization for a total hip arthroplasty. Today, he is readmitted for a pulmonary embolism. After 10 days of subcutaneous heparin (during hospitalization and rehabilitation), laboratory tests reveal a 50% drop in platelets, and there is concern for heparin-induced thrombocytopenia. Which of the following medications should be initiated in this patient?

A. Bivalirudin Heparin-induced thrombocytopenia (HIT) is suspected in this patient based on the > 50% decrease in platelets within 5-10 days of initial heparin exposure. HIT, an antibody-mediated complication, causes platelet activation and a paradoxical prothrombotic state. To reduce the risk of a blood clot or further clot expansion, heparin treatment must be discontinued, and full anticoagulation with a nonheparin anticoagulant initiated. The parenteral direct thrombin inhibitors argatroban and bivalirudin (Angiomax) are commonly used anticoagulants to treat HIT. Pharmacokinetic differences, comorbidities, and institutional practices help guide drug selection. Bivalirudin is renally eliminated, resulting in a prolonged half-life in kidney impairment. In comparison, argatroban, mainly hepatically metabolized and eliminated, has a prolonged half-life in hepatic impairment. (Choices B and C) Low molecular weight heparins (LMWHs) (dalteparin, enoxaparin) cause HIT at a lower rate (1 in 500) than unfractionated heparin (1 in 40). All forms of heparin, including LMWHs, are contraindicated if HIT is suspected. (Choice D) Ticagrelor (Brilinta), an oral P2Y12 inhibitor, reduces platelet aggregation. Ticagrelor does not provide adequate anticoagulation to treat or prevent a blood clot. (Choice E) Initial treatment of HIT with warfarin is contraindicated because warfarin rapidly decreases protein C levels (first 1-2 days), inducing a prothrombotic state. Warfarin can be started after treatment with a nonheparin anticoagulant once the platelet count recovers (≥ 150,000 cells/mm3). Things to remember:Heparin-induced thrombocytopenia is an antibody-mediated complication that causes low platelets and a prothrombotic state. Treatment includes discontinuing all forms of heparin (unfractionated heparin, low molecular weight heparin) and initiating a therapeutic-dose nonheparin anticoagulant (eg, argatroban, bivalirudin) to prevent blood clot development and expansion.

HB has been taking warfarin 6 mg daily for the past 4 months and all of her INR values have been within the therapeutic range (INR 2-3) in the past. Today, her INR is 3.2. She has been taking her medication the same way with no additional medications recently added to her regimen. What is the most appropriate management of HB's warfarin therapy at this time?

A. Continue taking warfarin 6 mg daily and test the INR within 1-2 weeks. The correct recommendation is to continue the current dose and recheck the INR within 1-2 weeks when the patient's previous INRs have been therapeutic and a single reading is within 0.5 of the therapeutic range.

A hospitalized patient is post-op day #1 after a right hip arthroplasty. The patient has a history of a previous VTE. The doctor has recommended that the patient begin warfarin with Lovenox bridge therapy, but the patient responds that he does not wish to take "rat poison". The pharmacy intern wants to explain the risks associated with not taking an anticoagulant in this situation. The intern should explain to the patient that he is at higher risk for the following complications if he chooses not to use anticoagulation: (Select ALL that apply.)

A. Deep vein thrombosis B. Pulmonary embolism 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). There are options aside from warfarin that may be acceptable to the patient.

A lower warfarin starting dose (≤ 5 mg) is recommended for which of the following patient populations: (Select ALL that apply.)

A. Elderly or debilitated B. Liver disease C. Heart failure D. Patients with a high risk of bleeding Rifampin is an inducer and requires a much higher dose, not lower.

KP is a 76-year-old male with a mechanical mitral heart valve, hypertension, type 2 diabetes, and hyperlipidemia. He was recently hospitalized for an elective procedure and discharged with a therapeutic INR of 2.8. Two weeks later he comes back for follow-up and reports that his gums have been bleeding. Which of the following natural products could increase KP's risk of bleeding? (Select ALL that apply.)

A. Glucosamine B. Vitamin E D. Ginger Vitamin E and the "5 G's" (garlic, ginger, ginkgo, ginseng and glucosamine) can increase the risk of bleeding in patients taking warfarin. St. John's wort is a CYP enzyme inducer that can increase the metabolism of warfarin, which leads to a lower INR and a higher risk of clotting.

Which of the following laboratory parameters need to be monitored during heparin therapy? (Select ALL that apply)

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

SM is a 62-year-old male who presents to the Emergency Department after a motor vehicle accident. Past Medical History: hypertension, anxiety, depression, atrial fibrillation, alcohol abuse Medications: Cardizem CD 180 mg daily, lisinopril 10 mg daily, sertraline 100 mg daily, Pradaxa 150 mg BID, Xanax 0.5 mg TID PRN Labs: Na (mEq/L) = 132 (135 - 145) K (mEq/L) = 5.1 (3.5 - 5) Cl (mEq/L) = 102 (95 - 103) HCO3 (mEq/L) = 30 (24 - 30) BUN (mg/dL) = 20 (7 - 20) SCr (mg/dL) = 1.3 (0.6 - 1.3) Glucose (mg/dL) = 189 (100 - 125) Ca (mg/dL) = 8.9 (8.5 - 10.5) Mg (mEq/L) = 1.7 (1.3 - 2.1) PO4 (mg/dL) = 2.6 (2.3 - 4.7) INR = 1.3 (0 - 1.2) PT (sec) = 19 (10 - 13)aPTT (sec) = 62 (22 - 38)WBC (cells/mm3) = 13.6 (4 - 11 x 103)Hgb (g/dL) = 9.2 (13.5 - 18 male)Hct (%) = 26.5 (38 - 50 male)Plt (cells/mm3) = 261 (150 - 450 x 103)AST (IU/L) = 39 (10 - 40) ALT (IU/L) = 35 (10 - 40)Albumin (g/dL) = 4.6 (3.5 - 5) Question: SM has sustained numerous internal injuries and will be going for emergency surgery. Which of the following should be recommended? (Select ALL that apply.)

A. Idarucizumab Idarucizumab (Praxbind) is a specific reversal agent for dabigatran, which this patient was taking prior to his motor vehicle accident. Patients taking dabigatran (and other novel anticoagulants) can experience altered PT/INR and PTT. These should normalize when dabigatran is antagonized or eliminated. Phytonadione and protamine would not be expected to have any effect in a patient not taking warfarin or heparin, respectively.

Select the correct mechanism of action for Pradaxa:

A. Oral direct factor IIa inhibitor Dabigatran (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.

A pharmacy receives a prescription for warfarin 5 mg PO daily. What is the color of the warfarin tablet?

A. Peach Warfarin 5 mg tablets are peach.

Which of the following medications will enhance warfarin's metabolism? (Select ALL that apply.)

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

Which of the following patients will require indefinite anticoagulation therapy if they are diagnosed with a venous thromboembolism? (Select ALL that apply)

A.A 27-year-old male with antithrombin III deficiency B. A 38-year-old male with factor V Leiden mutation D. A 50-year-old female with antiphospholipid syndrome F. A 66-year-old female with protein C deficiency Venous thromboembolisms (VTEs) can be provoked or unprovoked. Provoked VTEs usually result from temporary conditions such as a prolonged immobilization (eg, travel) or a recent surgery; these patients typically require a short duration of anticoagulation (eg, 3 to 6 months). Alternately, unprovoked VTEs usually result from underlying inherited or acquired thrombophilias (ie, tendency to form blood clots) or malignancy. Patients with underlying inherited or acquired thrombophilias often require indefinite anticoagulation due to the risk of severe and recurrent thromboembolism. Such conditions include: Factor V Leiden results from a single point mutation in the factor V gene that makes it unable to respond to activated protein C, an innate anticoagulant (Choice B). Antiphospholipid syndrome is an autoimmune condition characterized by the persistent presence of antiphospholipid antibodies (eg, lupus anticoagulant) (Choice D). Antithrombin III, protein C, and protein S are three of the body's natural anticoagulants; a deficiency in these proteins inhibits effective coagulation and increases the risk of clotting (Choices A and F). (Choice C) Factor VIII deficiency is a form of hemophilia. Patients with factor VIII deficiency cannot properly form a blood clot and are at high risk of bleeding, not clotting. (Choice E) Wernicke-Korsakoff syndrome is a neurologic syndrome that is the result of thiamine (vitamin B1) deficiency. It is often associated with chronic alcohol consumption but can occur in malnutrition or other conditions. There is no increased risk of clotting. Things to remember:Certain disease states (eg, cancer) and thrombophilias increase the risk of unprovoked venous thromboembolism. If a clot occurs, indefinite anticoagulation is warranted.

A patient has been using warfarin therapy for several years. He does not like the time it takes to report for lab monitoring. He asks if he can have his INR checked every six months. Which of the following represents the recommended monitoring schedule for patients who are well-controlled on a stable dose of warfarin?

B. The INR can be checked at up to 12-week intervals in stable patients 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.

Which of the following should be discussed with a patient receiving a new prescription for Pradaxa?

B. This medication must be kept in the original container. Do not put into a pill box. Dabigatran (Pradaxa) must be kept in the original container and discarded 4 months after opening the original container. Capsules must be swallowed whole.

GF is a 54-year-old female with a mechanical mitral valve, hypertension and GERD. What is the correct INR target range for GF?

B. 2.5-3.5 Goal INR range for patients with a mechanical mitral valve is 2.5.-3.5

LM is a 65-year-old female admitted to the hospital after undergoing a right lower extremity thrombectomy. Vital Signs: BP 92/60 mmHg, HR 115 bpm, Ht 66 in, Wt 69 kg Current Inpatient Medications:5% dextrose in water infusing at 50 mL/hrHeparin 25,000 units/250 mL infusing at 18 units/kg/hr The pharmacist is notified that LM has an active retroperitoneal hemorrhage. How much protamine should this patient receive based on her heparin drip rate over the last 2 hours?

B. 25 mg This patient has a life-threatening bleed (retroperitoneal hemorrhage) and should receive protamine, the reversal agent for unfractionated heparin (UFH), to minimize further bleeding. Protamine is a basic protein derived from fish sperm that has an anticoagulant effect when used alone but forms a stable salt when given in the presence of UFH (a strong acid). The protamine-UFH salt neutralizes the anticoagulant activity of both medications within minutes of IV administration. One milligram of protamine reverses 100 units of IV UFH. Due to the half-life of IV UFH, the amount received in the last 2-3 hours is used to determine the recommended dose of protamine. The following steps should be taken to determine the correct dose: Amount of UFH received in the last 2 hours 18 units/kg/hr × 69 kg = 1,242 units/hr × 2 hours = 2,484 units of UFH Dose of protamine needed to neutralize 2,484 units of UFH 2,484 units of UFH × 1 mg of protamine/100 units of UFH = 24.84 mg of protamine, which can be rounded up to 25 mg (Choices A, C, and D) Weight in kilograms must be used to calculate the total units of UFH received in the past 2 hours; 37 mg would be correct if asked how much protamine is needed to reverse the amount of UFH received over the last 3 hours. (Choice E) No more than 50 mg of protamine should be given in one dose due to the anticoagulant effect protamine can have at high doses, even in the presence of UFH. Things to remember:Protamine is the anticoagulation reversal agent for unfractionated heparin. One milligram of protamine will reverse the effects of 100 units of IV heparin; no more than 50 mg of protamine should be given in one dose.

(same as above) GH's physician would like to initiate stroke prophylaxis with Eliquis, but is unsure about dosing in the elderly. Which of the following is a correct dosing recommendation GH for stroke prophylaxis?

B. 5 mg BID Eliquis is dosed at 5 mg BID for stroke prophylaxis in atrial fibrillation, unless the patient meets two of the following criteria: age ≥ 80 years, weight ≤ 60 kg or SCr ≥ 1.5 mg/dL (then the dose is 2.5 mg BID).

The hospital pharmacist is completing her daily patient prophylaxis assessment and identifies which of the following patients that have at least one risk factor for developing a venous thromboembolism during their admission? (Select ALL that apply)

B. A 35-year-old pregnant female admitted for treatment of community-acquired pneumonia C. A 40-year-old female admitted for bariatric surgery for morbid obesity D. A 55-year-old female receiving Premarin for hot flashes E. A 60-year-old male who underwent a right knee replacement yesterday Venous thromboembolism (VTE) can occur for many reasons, but certain groups of patients are at a higher risk than the general population. Modifiable risk factors can be avoided, or have a finite timeframe associated with increased clotting risk. Nonmodifiable risk factors (eg, heritable diseases) put the patient indefinitely at an increased risk of clotting. Patients with risk factors for thromboembolic events often benefit from VTE prophylaxis if they are hospitalized. Several risk-scoring calculators are available (eg, Padua, IMPROVE, Geneva) to help guide decision-making. Obesity (ie, BMI ≥ 30 kg/m2) increases the risk of blood clots due to inflammation and impaired clot breakdown whereas surgery (eg, total knee replacement) and trauma increase a patient's risk of VTE for 30 days (Choices C and E). Pregnancy changes the plasma levels of many clotting factors, which increases the risk of VTE during pregnancy and postpartum (Choice B). Medications have also been associated with an increase in thromboembolic events. Those with the greatest risk include: Erythropoiesis-stimulating agents (eg, epoetin alfa) by increasing blood viscosity, platelet function, and hemoconcentration Estrogen-containing medications (eg, contraceptives, hormone replacement therapy) and selective estrogen receptor modulators (eg, tamoxifen) by increasing the activity of coagulation factors (Choice D) (Choice A) A nonsurgical patient under the age of 70 admitted for 24 hours with no known additional risk factors is not considered high risk for developing a blood clot and would not require VTE prophylaxis. Things to remember:Early identification and optimization of modifiable risk factors (eg, initiation of venous thromboembolism prophylaxis, medication discontinuation) decreases the risk of preventable blood clots.

SS went to an urgent care center for treatment of cellulitis. She was prescribed Bactrim DS PO BID x 10 days. How will the Bactrim DS affect her warfarin therapy?

B. Bactrim DS interacts with warfarin by increasing the INR. Recommend decreasing the warfarin dose and monitor closely. Sulfamethoxazole/trimethoprim (Bactrim) 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 the intestinal flora. This interaction can cause the INR to increase.

A 70-year-old patient was prescribed warfarin in the hospital for a deep vein thrombosis (DVT) in her right lower leg. She is being discharged, and the outpatient pharmacist who is going to dispense her warfarin is checking her medication profile for drug interactions. The pharmacist notes that the patient is using several medications which increase the risk of bleeding. She will counsel the patient on increased bleeding risk. Which of the following medications can increase her bleeding risk? (Select ALL that apply.)

B. Clopidogrel C. Flagyl D. Zoloft Clopidogrel (or any antiplatelet medication), metronidazole (Flagyl) and SSRIs/SNRIs (like sertraline) can increase the risk of bleeding in patients taking warfarin. Carbamazepine and St. John's wort are strong CYP inducers, which would increase the metabolism of warfarin and decrease the INR.

MH is a 63-year-old female with hypertension, chronic kidney disease, and degenerative joint disease. She is 5'3'', weighs 135 lbs, and has a serum creatinine of 2.5 mg/dL at the time of admission for hip replacement surgery. The provider orders enoxaparin 30 mg SC every 12 hours for deep vein thrombosis prophylaxis to start post-operatively. Which of the following actions is most appropriate for the pharmacist to take?

B. Contact the provider and recommend enoxaparin 30 mg SC every 24 hours Anticoagulants are used to prevent venous thromboembolism (VTE) in high-risk patients. Enoxaparin, a low molecular weight heparin (LMWH), is the preferred medication for VTE prophylaxis in most patients based on its efficacy, frequency of administration, and partial reversibility with protamine. The enoxaparin dose used for VTE prophylaxis is lower than the dose used to achieve therapeutic anticoagulation. The regimen is modified in patients with severely decreased kidney function to prevent accumulation and possible bleeding. To identify the most appropriate dosing regimen for a patient: 1. Calculate the patient's creatinine clearance (CrCl) using ideal body weight (IBW) CrCl = [140-6354.2 kg]722.5 ×0.85=19 mL/min 2. Determine the best dosing regimen based on the patient's CrCl CrCl ≥ 30 mL/min: 40 mg subcutaneously (SC) every 24 hours or 30 mg SC every 12 hours CrCl < 30 mL/min: 30 mg SC every 24 hours (Choice A) Enoxaparin 30 mg SC every 12 hours would be correct if the patient's CrCl was 30 mL/min or greater. The administration frequency should be every 24 hours based on this patient's creatinine clearance (CrCl 19 mL/min). (Choice C) Enoxaparin is administered subcutaneously, not intravenously, for VTE prophylaxis. In addition, it should be administered every 24 hours for a CrCl less than 30 mL/min. (Choice E) This dose and frequency (1 mg/kg SC every 24 hours) would be correct for the treatment of a VTE in a patient with a CrCl < 30 mL/min, not for VTE prophylaxis. Things to remember:Enoxaparin is a renally eliminated medication that is preferred for VTE prophylaxis in most patients. The standard doses are 40 mg SC every 24 hours or 30 mg SC every 12 hours; the dose is 30 mg every 24 hours when the CrCl is less than 30 mL/min.

A hospitalized patient developed a pulmonary embolism and was started on enoxaparin therapy. The physician began warfarin therapy on Monday and wrote an order to discontinue the enoxaparin therapy the following day. The pharmacist contacted the prescriber to recommend the following action:

B. Continue the enoxaparin for a minimum of 5 days and until the INR has been therapeutic for at least 24 hours. The parenteral anticoagulant should continue 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. Both of these criteria must be met.

A nurse practitioner wishes to convert a patient from warfarin to dabigatran. She asks the pharmacist how to manage the conversion. The pharmacist should offer the following advice:

B. Discontinue warfarin and start dabigatran when the INR is below 2. When converting patients from warfarin therapy to dabigatran, discontinue warfarin and start dabigatran when the international normalized ratio (INR) is below 2. Refer to the full prescribing information for recommendations on switching to and from warfarin and other oral anticoagulants.

CJ is a 44-year-old female (Ht 6′ 1″, Wt 198 lbs) with a newly diagnosed right lower extremity deep vein thrombosis. Laboratory Tests:Sodium 136 mEq/LPotassium 4.4 mEq/LChloride 99 mEq/LBicarbonate 24 mEq/LBUN 8 mg/dLCreatinine 1.1 mg/dLGlucose 100 mg/dL Which of the following is the correct enoxaparin dose for CJ?

B. Enoxaparin 90 mg SC every 12 hours Enoxaparin is a low molecular weight heparin (LMWH) anticoagulant used in the prevention and treatment of venous thromboembolism (VTE). Enoxaparin is administered subcutaneously (SC) when treating a VTE, reaches peak anticoagulant activity within 3-5 hours of administration, has a half-life of 7 hours, and is renally eliminated. The frequency of administration is decreased (eg, from Q12 hours to Q24 hours) in patients with severely decreased kidney function (eg, CrCl < 30 mL/min) to prevent accumulation and possible bleeding. Dosing of enoxaparin is based on total body weight (TBW) and kidney function when treating a blood clot. The following steps should be followed to determine the enoxaparin dose: Convert the patient's weight to kilograms (kilograms = pounds/2.2) Multiply the TBW by the appropriate dose (1 mg/kg or 1.5 mg/kg) Calculate the patient's creatinine clearance (CrCl)CrCl ≥ 30 mL/min: 1 mg/kg SC every 12 hours (or 1.5 mg/kg SC every 24 hours)CrCl < 30 mL/min: 1 mg/kg SC every 24 hours (Choice A) Ideal body weight was used in the dose calculation; enoxaparin is dosed using total body weight. (Choices C, D, and E) Enoxaparin is dosed based on TBW in kilograms. The standard dosing regimen for patients with a CrCl ≥ 30 mL/min is 1 mg/kg every 12 hours or 1.5 mg/kg every 24 hours. Things to remember:Enoxaparin is dosed 1 mg/kg subcutaneously every 12 hours (or 1.5 mg/kg every 24 hours) when treating a venous thromboembolism. It is dosed using total body weight and the regimen is modified when the creatinine clearance is less than 30 mL/min.

A pharmacy receives a prescription for warfarin 2.5 mg PO daily. What is the color of the warfarin tablet?

B. Green Warfarin 2.5 mg tablets are green.

KP is a 58-year-old female who is usually well-controlled on a warfarin regimen of 5 mg daily. She has been sick for the past week but feels better today. She ate little during her illness. She presents to the anticoagulation clinic to have her INR checked. Her INR is elevated today at 5.8. There is no noticeable bleeding, and she is at low risk of bleeding. Choose the preferred course of action:

B. Hold warfarin, monitor INR and resume warfarin at lower dose when the INR is in therapeutic range 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.

While working on the general medicine floor of the hospital, pharmacists are tasked with adjusting warfarin doses for some patients according to the hospital protocol below: DayINRWarfarin (mg)1Baseline52< 1.551.5-1.92.52-2.51> 2.5Hold3< 1.55-101.5-1.92.5-52-30-2.5> 3Hold4< 1.5101.5-1.95-7.52-30-5> 3Hold A 78-year-old patient with a PE has the following laboratory results and warfarin administration history:10/6 - Admission Date:Baseline INR = 1.2.Start warfarin 5 mg.10/7 - INR = 1.7. Warfarin 2.5 mg10/8 - INR = 2.8.Question:What recommendation on 10/8 would adhere to the hospital protocol?

B. Warfarin 1 mg With an INR of 2.8 on day #3 of therapy, a warfarin dose of 0-2.5 mg is appropriate according to the hospital protocol.

Which drug/s act via direct inhibition of factor Xa? (Select ALL that apply.)

B. Xarelto C. Savaysa E. Eliquis Xarelto, Savaysa and Eliquis are oral factor Xa inhibitors.

A 45-year-old male with a BMI of 32 kg/m2 asks to speak to the pharmacist about his risk of developing a blood clot during frequent, long-distance air travel for his job. Which of the following strategies are recommended to reduce venous thromboembolism risk in this patient? (Select ALL that apply)

B. Perform calf muscle exercises during the flight C. Choose to sit in an aisle seat E. Wear below-the-knee graduated compression stockings on the plane The risk of venous thromboembolism (VTE) after long-distance travel is relatively low in the general population but increases significantly in patients with at least one hypercoagulable risk factor (eg, BMI ≥ 30 kg/m2, age ≥ 40). Long-distance travel (air or automobile) can increase the risk of a blood clot for up to 8 weeks afterward, with the highest risk in the first 1-2 weeks. The pressure of a seat edge can cause endothelial damage, and sitting in a cramped space for an extended time can interfere with blood flow in the legs, leading to venous stasis. There are three measures recommended for all long-distance travelers to minimize venous stasis and prevent blood clots, and one additional measure recommended for all long-distance travelers with at least one VTE risk factor: Calf muscle exercises (Choice B) Frequent ambulation Sitting in an aisle seat (on an airplane) when possible (Choice C) With at least one VTE risk factor: below-the-knee graduated compression stockings (Choice E) (Choices A and D) Aspirin is not recommended for VTE prevention in long-distance travelers. Although it is not routinely recommended, an anticoagulant at prophylactic dosing (eg, rivaroxaban 10 mg daily) can be considered on a case-by-case basis for very high-risk patients (eg, history of prior VTE and prolonged travel). Things to remember:Long-distance travel increases the risk of venous thromboembolism. Nonpharmacologic prevention measures (eg, ambulation, calf exercises) are preferred in most individuals.

A 42-year-old female presents to the anticoagulation clinic for warfarin management. She has been taking 1.5 tablets of warfarin 5 mg daily for two months for a mechanical aortic valve. Her INR is 3.8 today. Clinic warfarin protocol INR Instructions < 1.5Increase weekly dose 10-20% 1.5-1.9Increase weekly dose 5-10% 2.0-3.0No change 3.1-4.0Decrease weekly dose by 5-10% 4.1-5.0Hold 1 dose and decrease weekly dose by 10% 5.1-9.0Prescriber order requiredHold 2 doses and decrease weekly dose by 10-20% > 9.0Contact prescriber for urgent evaluation Which of the following regimens will adhere to the clinic's warfarin protocol?

B. Prescribe 5mg tablets: take 1 tablet on Monday and Wednesday and 1.5 tablets on Sunday, Tuesday, Thursday, Friday, Saturday Warfarin (VKORC1 inhibitor) is a narrow therapeutic index drug. Dosage adjustment protocols usually recommend a small percentage increase or decrease in the total weekly dose to prevent overcorrection of the INR. There are many strategies to distribute the small dose change across the week, such as splitting tablets, using multiple tablet strengths, and changing to a new tablet strength. Patients should be carefully counseled on dosage changes, including tablet color. The patient's current warfarin regimen (7.5 mg/day, 52.5 mg/week) led to a supratherapeutic INR. The protocol recommends decreasing the weekly dose by 5-10% based on the current INR of 3.8. 5% reduction (52.5 mg × 0.05 = 2.625 mg) in weekly dose = 52.5 − 2.625 mg = 50 mg weekly. 10% reduction (52.5 mg × 0.1 = 5.25 mg) in weekly dose = 52.5 − 5.25 mg = 47.25 mg weekly. Therefore, a regimen providing 47.5 mg/week of warfarin is appropriate for this patient (Choice B). (Choices A and C) Reducing the dose from 52.5 mg/week to 38 mg/week (28% reduction) or 42 mg/week (20% reduction) will likely result in a subtherapeutic INR, which would increase the risk of clot development. (Choice D) Increasing the weekly dose (to 63 mg/week) will further increase the INR and the risk of bleeding. (Choice E) Warfarin is taken every day to prevent recirculation of vitamin K-dependent clotting factors and to maintain a stable INR. Things to remember:Warfarin is a narrow therapeutic index drug that must be adjusted in small increments (usually a percentage of the weekly dose) to obtain a goal INR.

While preparing for multidisciplinary rounds, the pharmacist notices that a patient was started on unfractionated heparin 5,000 units SC every 8 hours. Which of the following is an appropriate indication for this order?

B. Prophylaxis of venous thromboembolism Anticoagulants (eg, unfractionated heparin) are routinely used to prevent venous thromboembolisms (VTEs) in high-risk patients. The total daily doses used in VTE prophylaxis are lower than those required to achieve therapeutic anticoagulation. Unfractionated heparin 5,000 units is administered subcutaneously every 8-12 hours for prevention of venous thromboembolisms. The choice of medication for VTE prophylaxis is based on pharmacokinetic properties and patient-specific factors. Unfractionated heparin is preferred over alternate agents (eg, enoxaparin) in patients with: Highest risk of bleeding due to heparin's shorter half-life and rapid reversibility with protamine Acute kidney injury or with end-stage renal disease because heparin is not renally eliminated (Choices A, C, and D) Therapeutic doses of anticoagulation are used for the prevention of cardioembolic stroke in patients with atrial fibrillation, treatment of a pulmonary embolism, and treatment of an ST-segment elevation myocardial infarction. An IV bolus, followed by a continuous infusion of unfractionated heparin with routine monitoring, is required. Initial bolus dose and infusion rate will vary based on the indication; goal activated partial thromboplastin time (aPTT) will vary based on the indication and institution. Things to remember:Unfractionated heparin 5,000 units subcutaneously every 8-12 hours can be used to prevent the development of blood clots in hospitalized patients; it is often preferred in patients with a high bleeding risk or with significant renal impairment.

Which of the following are signs/symptoms that could indicate a patient is bleeding? (Select ALL that apply.)

B. Red or black stools C. Epistaxis D. Metallic taste in mouth when she brushes her teeth E. Ecchymosis Epistaxis is the technical term for a nose bleed. Ecchymosis is bruising. Blood contains iron and tastes metallic. If a patient's gums are bleeding when they are brushing their teeth, they may notice this metallic taste. Other signs of bleeding could include pain, swelling, or discomfort, bleeding from cuts that take a long time to stop (usually more than 15 minutes), menstrual bleeding or vaginal bleeding that is much heavier than normal, pink or brown urine (or dark, tarry stools) or vomiting blood or material that looks like coffee grounds (hematemesis). Dark tarry stools are more likely with NSAID-induced bleeding but would be aggravated by an elevated INR.

HL is taking Xarelto 15 mg PO twice daily at 9 AM and 9 PM for a newly diagnosed deep vein thrombosis. HL calls the pharmacy at 4 PM and states that he forgot to take his 9 AM dose of Xarelto. What should the pharmacist instruct HL to do?

B. Take on 15mg tablet now and resume scheduled dosing at 9 PM tonight Drug characteristics (eg, food requirements, dosing intervals, drug level timing) are used to provide counseling on missed doses of medications. Incorrectly taking a missed dose can cause harm or unintended consequences (eg, a phosphate binder taken without food will not work). For most medications, a missed dose should be taken as soon as the patient remembers, and doses should not be doubled-up. Exceptions are oral contraceptive pills (missed doses are occasionally doubled-up) and the initial venous thromboembolism (VTE) dosing of rivaroxaban (Xarelto). Dosing of rivaroxaban for VTE is 15 mg PO BID for 21 days, followed by 20 mg PO daily with missed doses taken as follows: 15 mg tablet PO BID: Take the missed dose immediately. Two tablets may be taken at the same time. 20 mg tablet PO once daily: Take the dose immediately. If it is already the next day, skip the missed dose. Two 20 mg tablets should not be taken on the same day. (Choices A and D) One and a half rivaroxaban 15 mg tablets in a day will result in a total dose of 22.5 mg. This is less than the required total daily dose of 30 mg. (Choices C and E) Taking one 15 mg rivaroxaban tablet per day to treat a blood clot will not provide adequate anticoagulation. Things to remember:Most missed doses should be taken as soon as the patient remembers, and doses should not be doubled. The exceptions are oral contraceptives and rivaroxaban (Xarelto) 15 mg PO twice daily, for which two tablets may be taken simultaneously.

SK is a 55-year-old female with a mechanical aortic heart valve, diabetes and osteoporosis. What is the recommended therapeutic INR range of warfarin for this patient?

C. 2-3 Patients with a mechanical aortic valve should have an INR between 2-3. Patients with 2 mechanical valves or a single mechanical mitral valve require a higher INR goal (2.5-3.5) because these scenarios are associated with greater risk of clotting.

A 55-year-old man (weighing 222 lbs) comes into the emergency department with crushing chest pain. His creatinine clearance is estimated at 45 mL/min. The physician makes the diagnosis of ST-segment elevation myocardial infarction (STEMI) and wants to initiate enoxaparin right away. What is the correct dose of enoxaparin in this patient?

C. 30 mg IV bolus plus 100 mg SC every 12 hours started immediately after the bolus 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 first two doses) if CrCl > 30 mL/min.

A patient is being started on warfarin therapy. Which of the following scenarios would pose an increased risk of bleeding from warfarin?

C. Also taking a 2C9 inhibitor 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.

A patient has used warfarin daily for many years. She usually takes the warfarin at 6:00 PM with dinner. She calls the pharmacy because she got stuck in a snowstorm yesterday and could not return home to take her warfarin dose last night. It is now 4:00 PM the following day. She asks the pharmacist if she should take yesterday's warfarin dose now. The pharmacist should offer the following advice:

C. Do not take yesterday's dose; missed doses should not be taken on the following day

HT is a 25-year-old male with congenital cardiomyopathy and atrial fibrillation. He is 6'2", weighs 187 lbs and has an allergy to sulfa. Labs: Na (mEq/L) = 142 (135 - 145) K (mEq/L) = 4.1 (3.5 - 5) Cl (mEq/L) = 100 (95 - 103) HCO3 (mEq/L) = 25 (24 - 30) BUN (mg/dL) = 18 (7 - 20) SCr (mg/dL) = 0.5 (0.6 - 1.3) Glucose (mg/dL) = 112 (100 - 125) Ca (mg/dL) = 8.7 (8.5 - 10.5) Mg (mEq/L) = 1.9 (1.3 - 2.1) PO4 (mg/dL) = 2.5 (2.3 - 4.7) Albumin (g/dL) = 3.4 (3.5 - 5) PT (sec) = 12 (10 - 13) INR = 1 WBC (cells/mm3) = 6.3 (4 - 11 x 103) Hgb (g/dL) = 13.4 (13.5 - 18 male, 12 - 16 female) Hct (%) = 37 (38 - 50 male, 36 - 46 female) Plt (cells/mm3) = 246 (150 - 450 x 103) AST (IU/L) = 41 (10 - 40) ALT (IU/L) = 38 (10 - 40) Question: Which of the following anticoagulant options should not be used for stroke prophylaxis in this patient?

C. Edoxaban Edoxaban (Savaysa) should not be used in patients with CrCl > 95 mL/min due to reduced efficacy in this patient population treated for nonvalvular atrial fibrillation.

AZ currently has lung cancer and was diagnosed with a DVT. Her estimated CrCl is 75 mL/min. Which of the following anticoagulants is preferred for this patient?

C. Enoxaparin 1 mg/kg SC q12h LMWH (in a treatment dose) is preferred over warfarin for treating a DVT in a patient with cancer.

A 43-year-old female comes to the clinic for an appointment. The patient has been on warfarin 6 mg daily for three months with a stable INR in her goal range of 2-3. Today she experienced a nosebleed and noticed some bruising on her arms. Past Medical History: antiphospholipid syndrome, deep vein thrombosis, myasthenia gravis Home Medications (verified from outpatient pharmacy records 3 weeks ago):Prednisone 20 mg PO dailyPyridostigmine 60 mg PO five times a dayWarfarin 6 mg PO daily Laboratory Tests:Serum creatinine 0.8 mg/dLINR 4.8 Recent initiation of which medication would explain the patient's INR change?

C. Fluconazole Warfarin (Coumadin, Jantoven), a vitamin K epoxide reductase (VCORC1) inhibitor, is metabolized in the liver by CYP450 2C9, 1A2, 2C19, and 3A4. Initiation or discontinuation of drugs that impact these CYP enzymes, especially CYP2C9 (ie, metabolizes the more potent enantiomer), can alter warfarin serum concentration and the anticoagulant effect. Elevations in serum warfarin levels increase the INR and, potentially, the risk of bleeding. Fluconazole (Diflucan), an azole antifungal, is a strong inhibitor of CYP2C19 and a moderate inhibitor of CYP2C9 and 3A4. When fluconazole is initiated in a patient on warfarin, serum levels of warfarin and the INR will increase if the warfarin dose is not decreased. (Choices A and E) Carbamazepine and rifampin are CYP enzyme inducers. When inducers of CYP2C9, 1A2, 2C19, or 3A4 are initiated in a patient on warfarin, serum levels of warfarin and the INR will ultimately decrease if the warfarin dose is not increased. (Choice B) Estradiol/drospirenone, an estrogen and progestin combination product used for menopausal symptoms, can increase the risk of blood clots but does not directly interact with warfarin. (Choice D) When given with warfarin, the NSAID indomethacin (Indocin) can increase the risk of bleeding due to impaired thromboxane-dependent platelet aggregation, but it is not expected to impact the INR. Things to remember:Initiation of fluconazole in a patient on warfarin will lead to an increased anticoagulant effect (increased INR) by increasing warfarin serum levels via inhibition of CYP450 2C19, 2C9, and 3A4.

CJ is a 44-year-old female with hyperlipidemia and hypertension. She is referred to a pharmacist-managed anticoagulation clinic with a newly diagnosed, first unprovoked episode of lower left leg DVT. She is a teacher and drinks 1 glass of wine per day. Lab/vitals: Weight: 325 lbs, Height: 6'1", Scr 0.6 mg/dL (1 month ago), Baseline INR 1.1. What INR goal and duration of warfarin therapy should be recommended to treat CJ's DVT?

C. INR goal of 2-3 for at least 3 months Guidelines recommend that the first, unprovoked VTE be treated for at least 3 months with anINR goal of 2-3.

A 68-year-old male comes to the emergency department due to severe back pain and dizziness. Past Medical History: atrial fibrillation, dyslipidemia, hypertension Home Medications:Atorvastatin 20 mg PO HSLisinopril 10 mg PO dailyMetoprolol 50 mg PO dailyWarfarin 5 mg PO daily Vital Signs: BP 88/42 mmHg, HR 92 bpm, RR 15 bpm, O2 sat 93% on room air, T 99°F (37.2°C), Ht 70", Wt 188 lbs Laboratory Tests:White blood cells 7,500 cells/mm3Hemoglobin 8 g/dLHematocrit 24%Platelets 131,000 cells/mm3INR 3.2 Diagnostic Tests:CT scan of the abdomen: acute retroperitoneal hemorrhage Which of the following are the most appropriate drugs to administer to this patient? (Select ALL that apply)

C. Kcentra D. Phytonadione Patients with life-threatening bleeding (eg, retroperitoneal hemorrhage) requiring warfarin (vitamin K antagonist) reversal should receive prothrombin complex concentrate (PCC). PCC is a blood product that contains vitamin K-dependent clotting factors. Four-factor PCC (Kcentra), preferred for warfarin reversal, has therapeutic amounts of all vitamin K-dependent clotting factors (eg, II, VII, IX, X) and protein C and S. In comparison, some factor products contain a single factor [eg, factor VIIa recombinant (NovoSeven RT)], and 3-factor PCC (Profilnine) contains factors II, IX, X, protein C and S, and variable, nontherapeutic amounts of factor VII. Four-factor PCC rapidly normalizes the INR (within 30 minutes for most patients); however, the effects are transient (8-12 hours) (Choice C). Phytonadione (synthetic vitamin K) works to maintain factor levels once the effects of PCC have diminished by acting as a cofactor to vitamin K-dependent clotting factor synthesis (Choice D). Fresh frozen plasma can be given if PCC is unavailable, but it is less desirable because of the large volume required and preparation time. (Choice A) The antidote andexanet alfa (Andexxa) binds to and sequesters factor Xa inhibitors (apixaban, rivaroxaban), reversing the anticoagulant effect. (Choice B) IV desmopressin, a synthetic analog of antidiuretic hormone, increases circulating levels of factor VIII and von Willebrand factor. It is used to stop bleeding in patients with mild hemophilia A and mild von Willebrand factor disease. (Choice E) Idarucizumab (Praxbind) is a monoclonal antibody that reverses the anticoagulant effect of the direct thrombin inhibitor dabigatran (Pradaxa). Things to remember:Life-threatening bleeding from warfarin should be reversed with 4-factor prothrombin complex concentrate (PCC) and IV vitamin K. If PCC is unavailable, fresh frozen plasma can be given.

GG is a 68-year-old male with persistent atrial fibrillation who comes to the hospital on May 1 for a planned cardioversion. He has completed an appropriate duration of precardioversion anticoagulation with apixaban. If GG remains in normal sinus rhythm following cardioversion, what is the earliest date that apixaban can be discontinued?

C. May 28 Atrial fibrillation (AF) leads to inadequate blood flow through the heart, increasing the risk of a left atrial thrombus. If normal sinus rhythm is restored spontaneously, pharmacologically, or electrically in a patient with AF, a thrombus can be dislodged, causing a cardioembolic stroke. Direct-current cardioversion can also stun the atria, causing atrial thrombus formation. To minimize the risk of stroke, most patients require anticoagulation for three weeks before and four weeks after cardioversion. Select patients may have transesophageal echocardiography (TEE) performed to rule out the presence of a thrombus before cardioversion is performed. Hemodynamically unstable patients with AF may receive cardioversion without anticoagulation when the need to quickly restore organ perfusion outweighs the risk of precipitating a cardioembolic stroke. (Choice A) Males with a CHA2DS2-VASc score of 0 or females with a score of 1 with AF lasting less than 48 hours do not require anticoagulation following cardioversion in all situations. Other patients should receive anticoagulation. (Choice B) Three weeks is the required duration of anticoagulation before cardioversion. (Choices D and E) Following successful cardioversion, anticoagulation is continued for one month, not three months (treatment duration for a first-time provoked venous thromboembolism) or one year. Things to remember:Most patients undergoing cardioversion for atrial fibrillation receive anticoagulation for three weeks before and four weeks after the procedure to reduce the risk of a cardioembolic stroke.

Chief Complaint: "I can't walk it hurts so bad." History of Present Illness: ST is a 72-year-old female who was recently hospitalized for 10 days for a heart failure exacerbation and pneumonia. Today she presents to the ER with left lower extremity swelling that started last week. Her leg became more swollen and painful over the past few days until she could no longer apply weight to her left leg. Allergies: NKDA Past Medical History: Hypertension, type 2 diabetes, heart failure, gout Medications: Lantus 24 units QHS, Novolog 3 units TID before meals, Diovan HCT 160 mg/25 mg daily, Coreg CR 20 mg daily, Neurontin 600 mg TID, Lasix 20 mg daily Physical Exam / Vitals: Height: 5'4" Weight: 200 lbs Vitals: BP: 167/92 HR: 92 BPM RR: 16 BPM Temp: 98.8 F O2 sat: 98% Pain: 8/10 General: Obese female with painful left lower extremity. Appears stated age. Cardiovascular: RRR Lungs: CTA bilaterally Extremities: Left calf circumference > right. Swollen from ankle to knee on left. No swelling on right. Warm to touch, no lesions or infection. Labs: Na (mEq/L) = 142 (135 - 145)WBC (cells/mm3) = 5.7 (4 - 11 x 103)K (mEq/L) = 3.7 (3.5 - 5)Hgb (g/dL) = 11.2 (13.5 - 18 male, 12 - 16 female)Cl (mEq/L) = 99 (95 - 103)Hct (%) = 34 (38 - 50 male, 36 - 46 female)HCO3 (mEq/L) = 27 (24 - 30)Plt (cells/mm3) = 322 (150 - 450 x 103)BUN (mg/dL) = 31 (7 - 20)AST (IU/L) = 29 (10 - 40) SCr (mg/dL) = 1.2 (0.6 - 1.3)ALT (IU/L) = 34 (10 - 40)Glucose (mg/dL) = 202 (100 - 125)Albumin (g/dL) = 3.4 (3.5 - 5) Ca (mg/dL) = 9.7 (8.5 - 10.5)A1C (%) = 10.1Mg (mEq/L) = 1.7 (1.3 - 2.1)PT (sec) = 13 (10 - 13)PO4 (mg/dL) = 2.8 (2.3 - 4.7)INR = 0.8 Tests:Ultrasound of left lower extremity: DVTEKG: NSR, no ST or T wave changesPlan: Admit to the medical floor for treatment of DVT and management of other chronic conditions. The physician plans to start ST on enoxaparin, but would like to order a laboratory test to monitor efficacy of enoxaparin therapy. Which of the following could be recommended?

C. Peak anti-Xa, 4 hours after the dose Anti-Xa levels should be drawn 4 hrs after the SQ dose (peak). Routine monitoring of enoxaparin with anti-Xa levels is not necessary in most patients but can be done in certain patients (e.g., extreme body weight or renal dysfunction).

QZ is a 32-year-old male admitted to the surgical intensive care unit for the management of multiple bone fractures after a motor vehicle crash. Drug Allergies: Bactrim (anaphylaxis) Inpatient Medications:Hydromorphone 10 mcg/mL + bupivacaine 0.1% epidural to infuse at 6 mL/hrHydromorphone 0.2 mg IV every 10 minutes PRN severe breakthrough painPercocet 10 mg/325 mg PO every 6 hoursIbuprofen 800 mg PO every 8 hoursCefazolin 2 g IV every 8 hours The following day, the provider orders enoxaparin for venous thromboembolism prophylaxis. Administration of enoxaparin places this patient at risk for which of the following adverse effects?

C. Spinal hematoma This patient is currently receiving an epidural, a type of neuraxial procedure that is used as an adjunct to oral or intravenous medications for the management of acute, severe pain. To administer a medication via epidural, a needle must be inserted between the vertebrae and into the epidural space; a small catheter is then left in place to maintain access. This is a high-risk area because of proximity to the spinal cord. Administration of anticoagulation (even prophylactic doses) while an epidural catheter is in place puts the patient at an increased risk of developing a spinal or epiduralhematoma. Low molecular weight heparins (eg, enoxaparin), oral factor Xa inhibitors (eg, apixaban), and dabigatran all carry a boxed warning against concomitant use, as these may lead to long-term or permanent paralysis. (Choice A) Enoxaparin can cause hyperkalemia, not hypokalemia, by suppressing aldosterone production. (Choice B) Long-term use of corticosteroids or use of bisphosphonates (eg, alendronate) can cause osteonecrosis, whereas long-term (> 6 months) use of enoxaparin may cause osteoporosis due to the reduction in bone mineral density. (Choice D) Toxic epidermal necrolysis is a life-threatening skin disorder characterized by blistering and peeling of the skin. It is often caused by antibiotics or antiepileptics, not anticoagulants. Things to remember:Administration of enoxaparin (even prophylactic doses) in a patient with an epidural should be avoided as it puts the patient at increased risk of a spinal or epidural hematoma, which can lead to paralysis.

A pharmacy technician trainee is preparing a batch of heparin bags based on the standard compounding formula provided below. During final verification, the pharmacist notices that 25 mL of unfractionated heparin 10,000 units/mL was used while compounding. Which of the following would most likely occur if this bag of heparin is administered to a patient?

C. Supratherapeutic activated partial thromboplastin time leading to an increased risk of bleeding. Anticoagulants [eg, unfractionated heparin (UFH)] are considered high-risk medications because they can cause serious patient harm or death when used in error. Safeguards should be in place throughout the medication process (eg, ordering, compounding, delivery, administration) to minimize this risk. UFH has many commercially available concentrations with nearly identical packaging that are used in different settings (eg, heparin lock flush versus heparin for systemic anticoagulation). Pharmacists must pay attention to drug concentrations when compounding because of the impact an error can have on the patient. Routine monitoring of UFH with an activated partial thromboplastin time (aPTT) is one way to ensure that the patient is safely and effectively anticoagulated; an aPTT above the target range indicates a patient is receiving too much anticoagulation. Administration of a heparin product that contains 10 times the expected amount of UFH would over-anticoagulate the patient and increase the risk of a serious bleeding event (eg, intracranial hemorrhage). (Choices A and B) A subtherapeutic aPTT (in a patient on anticoagulation) occurs when the patient is not receiving enough anticoagulation; this increases the risk of clotting, not bleeding. (Choice D) A supratherapeutic aPTT indicates over-anticoagulation; this increases the risk of bleeding, not clotting. (Choice E) A patient will have a therapeutic aPTT when properly anticoagulated; this is the expected outcome when the correct concentration of UFH (10,000 units/10 mL) is used during compounding and administered to the patient. Things to remember:Anticoagulants (eg, unfractionated heparin) are high-risk medications that can lead to serious patient harm when used in error. Use of the correct concentration during compounding and laboratory monitoring during administration can decrease the risk of patient harm.

Which of the following organizations sets the guidelines for the management of antithrombotics?

C. The American College of Chest Physicians (ACCP): Evidence-Based Clinical Practice Guidelines, published in the journal CHEST 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

JK is a 62-year-old female with chronic urinary tract infections. Several times a year, she receives a prescription for Bactrim. JK comes to the pharmacy today with a prescription for warfarin with 11 refills. The pharmacist should emphasize the following counseling to this patient: (Select ALL that apply.)

C. The drug interaction between warfarin and Bactrim may lead to significant bleeding. E. She will need more frequent INR monitoring when starting or stopping Bactrim. Bactrim can inhibit the metabolism of warfarin putting the patient at risk for bleeding. All providers treating the patient should know that she is taking warfarin to prevent drug-drug interactions.

CD is a 66-year-old male who presents to the emergency department with a painful and swollen right leg. The patient reports that the pain and swelling began yesterday after he drove for 14 hours. Past Medical History: hypertension, obesity, chronic kidney disease Home Medications: amlodipine 5 mg PO daily, lisinopril 10 mg PO daily Vital Signs: BP 130/80 mmHg, HR 84 bpm, RR 14 bpm, O2 sat 96% on room air, T 101.8°F (38.8°C), Ht 5′10″, Wt 253 lbs Laboratory Tests:Serum creatinine 1.7 g/dL Diagnostic Tests:Ultrasound: right lower extremity deep vein thrombosis What is the correct dose of oral apixaban for CD?

D. 10 mg twice daily for 7 days, then 5 mg twice daily The patient has a deep vein thrombosis (DVT). The direct-acting factor Xa inhibitors apixaban (Eliquis) and rivaroxaban (Xarelto) require higher doses in the initial treatment period following a DVT given the risk of progression to a pulmonary embolism. A lower maintenance dose follows the initial treatment period. Both apixaban and rivaroxaban have convenient starter packs containing the higher initial doses and the lower doses to prevent medication errors. The apixaban dose for an acute venous thromboembolism (VTE) is 10 mg PO twice daily for the first 7 days, followed by 5 mg PO twice daily for the remainder of the treatment. (Choices A and B) Apixaban 2.5 mg PO twice daily is the approved dose for VTE prophylaxis. It is also used to prevent strokes in patients with atrial fibrillation who have any two of the following indicators: weight ≤ 60 kg, age ≥ 80 years, or serum creatinine ≥ 1.5 mg/dL. The dose for other patients with atrial fibrillation is 5 mg PO twice daily. In atrial fibrillation, there is no need for an initial aggressive treatment period. (Choices C and E) Rivaroxaban 20 mg PO daily is approved for the prevention of strokes in patients with atrial fibrillation and a CrCl of at least 50 mL/min. For the treatment of a VTE, rivaroxaban is dosed at 15 mg PO twice daily for 21 days, then 20 mg PO daily. Things to remember:The direct-acting factor Xa inhibitors apixaban and rivaroxaban require higher doses in the initial treatment period following a venous thromboembolism. The apixaban dose for an acute venous thromboembolism is 10 mg PO twice daily for the first 7 days, followed by 5 mg PO twice daily for the remainder of the treatment.

KL is a 28-year-old female who comes to the emergency department with pain and swelling in her left lower extremity. She states that the pain and swelling began yesterday after her flight from Hawaii to Texas. Past Medical History: allergic rhinitis Home Medications: Claritin 10 mg PO daily, Seasonique 1 tablet PO daily Vital Signs: BP 128/78 mmHg, HR 84 bpm, RR 14 bpm, T 98.5°F (36.9°C), Ht 60 in, Wt 138 lbs Diagnostic Tests:Ultrasound: left lower extremity deep vein thrombosis Which of the following is preferred for the treatment of KL's deep vein thrombosis?

D. Eliquis A provoked venous thromboembolism (VTE) is caused by one or more known risk factors. A provoked deep vein thrombosis (DVT) should be treated for three months with an anticoagulant. For most hemodynamically stable patients, direct-acting oral anticoagulants [oral factor Xa inhibitors (eg, apixaban) and dabigatran (Pradaxa)] are preferred over warfarin (INR goal of 2 to 3) due to decreased monitoring requirements and similar safety profiles. If there is a contraindication to the use of an oral factor Xa inhibitor or dabigatran, warfarin with a parenteral anticoagulant bridge (eg, enoxaparin) is an option. (Choice A) Alteplase (Activase) is a fibrinolytic approved for systemic use in the treatment of massive pulmonary embolism that results in hemodynamic instability. Because the risk of life-threatening bleeding (eg, intracranial) is high compared to anticoagulants, thrombolytics are not indicated in stable VTE patients. Alteplase can also be used locally (via catheter-directed thrombolysis) in combination with low-dose heparin to treat select VTEs. (Choice B) Ticagrelor (Brilinta) is an antiplatelet medication that is primarily used in the treatment or secondary prevention of an acute coronary syndrome (ie, stent restenosis), not for the treatment of venous thromboembolic events. (Choice C) Cilostazol is an antiplatelet medication with vasodilatory properties used in the management of intermittent claudication (peripheral artery disease). There is a boxed warning against its use in patients with heart failure of any severity. Things to remember:The preferred treatment for a provoked deep vein thrombosis in most hemodynamically stable patients is three months of an oral factor Xa inhibitor or dabigatran.

A female patient who is pregnant has been admitted to the hospital with a DVT. The physician will begin heparin therapy. What is the mechanism of action of heparin?

D. Heparin potentiates antithrombin Heparin binds to antithrombin and then inactivates factor IIa (thrombin) and factor Xa.

JD is a 76-year-old male (height 5′7″, weight 200 lbs) with a mechanical mitral heart valve, hypertension, type 2 diabetes mellitus, and hyperlipidemia. JD will be undergoing a major elective surgical procedure and is considered high-risk for thromboembolism. Medications:Lisinopril 40 mg PO dailyLovastatin 40 mg PO daily with dinnerMetformin 850 mg PO twice dailyWarfarin 7.5 mg PO daily Laboratory Tests:Serum creatinine 0.85 mg/dLINR 2.9 What is the best perioperative anticoagulation plan for this patient?

D. Hold warfarin for 5 days prior to the procedure. Bridge with enoxaparin 90 mg subcutaneously twice daily. Oral anticoagulants (eg, warfarin) are discontinued before surgery to minimize the risk of major bleeding. Warfarin is held for 5 days (half-life ~40 hours) prior to surgery, which results in normalization of the INR (ie, INR < 1.5) in most patients. Thrombotic risk is assessed to determine the need for an anticoagulant with a shorter half-life while the oral anticoagulant is held perioperatively. Patients at high risk for developing a clot (eg, mechanical valve) should receive treatment-dose parenteral anticoagulant once the INR is subtherapeutic. The anticoagulant dosing is as follows: Intravenous unfractionated heparin (UFH): adjusted per hospital policy to a therapeutic activated partial thromboplastin time (aPTT) (or antifactor Xa levels in select patients or institutions); discontinue 4-6 hours before surgery. Subcutaneous enoxaparin: 1 mg/kg every 12 hours; discontinue 24 hours before surgery. (Choices A and B) Holding warfarin for 2 days is not an adequate amount of time for the INR to normalize. (Choice C) Routine administration of preoperative vitamin K is not recommended. Oral vitamin K takes 24-48 hours to reach peak effect and prolongs the time to a therapeutic INR when warfarin is restarted. However, low-dose oral vitamin K (1-2.5 mg) can be used if the INR is elevated the day before surgery to prevent blood product administration or surgery delays. (Choice E) Enoxaparin is dosed according to patient weight in kilograms, not pounds. Things to remember:Warfarin is held 5 days before major surgery to decrease the risk of severe bleeding. Patients at high risk of thrombosis should receive perioperative treatment-dose parenteral anticoagulation once the INR is subtherapeutic.

A 55-year-old male receives phytonadione 10 mg intravenously in the emergency department. Which of the following adverse drug reactions should the patient be monitored for?

D. Hypersensitivity reaction Phytonadione (synthetic vitamin K) is used to reverse the effects of warfarin, prevent/treat vitamin K deficiency, and treat coagulopathy in patients with liver disease (off-label). Phytonadione acts as a cofactor to vitamin K-dependent clotting factor synthesis, which replenishes endogenous clotting factors. Intravenous and intramuscular administrations of phytonadione are generally avoided due to safety concerns (boxed warning for hypersensitivity) but can be given when other routes (eg, oral, subcutaneous) are not feasible or not recommended. The hypersensitivity reaction from phytonadione (previously called an anaphylactoid reaction) is IgE-independent and can result in cardiac arrest. Strategies to minimize a hypersensitivity reaction include the following: Dilute the drug in a minimum of 50 mL 0.9% sodium chloride or 5% dextrose. Administer the lowest required dose at a slow rate, not to exceed 1 milligram per minute. (Choice A) Acute interstitial nephritis is a type of acute kidney injury frequently associated with NSAIDs, proton pump inhibitors, and some antibiotics (eg, aminoglycosides, amphotericin B), not phytonadione. It usually occurs after repeated exposure (a few days later) to the offending drug. (Choices B and E) Dystonia and neuroleptic malignant syndrome are precipitated by antipsychotics, not phytonadione. (Choice C) Hyperkalemia (high potassium) can be caused by many drugs, including those that act on the renin-angiotensin-aldosterone system (eg, ACE inhibitors) and potassium-sparing diuretics. Phytonadione is not associated with hyperkalemia. Things to remember:Due to the risk of hypersensitivity reactions, intravenous phytonadione is reserved for situations when other routes of administration are not feasible or not recommended. To mimimize the risk of a hypersensitivity reaction, the drug must be diluted in a minimum of 50 mL and administered at a slow rate, not to exceed 1 milligram per minute.

PW is a 64-year-old female who is taking warfarin for atrial fibrillation. She has a past medical history significant for HTN, type 2 diabetes, back pain and a previous CVA in 2008. PW is a retired nurse and does not drink alcohol or smoke. Medications: Prinzide Lopressor Coumadin Glucophage Victoza Labs: Wt: 160 lbs Ht: 5'1" SCr: 1.2 mg/dL KP complains that her back pain is worsening and wants to take Advil or Doan's for pain relief. The pharmacist should provide the following counseling:

D. It is not safe to take either Advil or Doan's while on warfarin. 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. Both are popular OTC products. Acetaminophen is the analgesic of choice when a patient is on warfarin.

A patient is being started on Pradaxa. Choose the correct statement regarding Pradaxa:

D. Once a bottle of Pradaxa is opened, the capsules must be used within 120 days The 60-count bottles of Pradaxa expire 4 months after opening the bottle.

A 63-year-old male is brought to the cardiac stepdown unit from the cardiac catheterization laboratory following a percutaneous coronary intervention. Since admission, the patient has received aspirin, metoprolol, ticagrelor, fentanyl, and IV unfractionated heparin. Five minutes after arrival to the stepdown unit, he reports a severe headache. CT scan reveals an acute intracerebral hemorrhage. Vital Signs: BP 110/80 mmHg, HR 102 bpm, RR 20 bpm, O2 sat 95% on room air, T 97.7°F (36.5°C) Laboratory Tests:White blood cells 11,000 cells/mm3Hemoglobin 13 g/dLHematocrit 39%Platelets 130,000/mm3Activated partial thromboplastin time 155 seconds Which of the following should be given to the patient to minimize further bleeding?

D. Protamine sulfate This patient has life-threatening bleeding in his brain precipitated by high-dose unfractionated heparin (UFH) received during percutaneous coronary intervention. Anticoagulation reversal is indicated to minimize further bleeding. Protamine, a mixture of proteins derived from fish sperm, is the reversal agent of choice for heparins [UFH, low molecular weight heparin (LMWH)]. The anticoagulation effects of UFH are reliably neutralized with protamine administration (based on the amount of IV UFH received in the past 2-3 hours). Protamine is also used as a reversal agent for LMWHs, but it does not completely reverse the anti-Xa activity. Vital signs are closely monitored during protamine administration due to the boxed warning for severe hypersensitivities. This risk increases with rapid administration (maximum infusion rate is 5 mg/min), presence of a fish allergy, and previous protamine exposure. (Choice A) In conjunction with vitamin K, 4-factor prothrombin complex concentrate (KCentra) (factors II, VII, IX, and X) is used to reverse major bleeding from warfarin. (Choice B) Idarucizumab (Praxbind) is a humanized monoclonal antibody fragment that binds to and reverses the effects of dabigatran (Pradaxa). (Choice C) Platelets are not given to reverse anticoagulation. Heparin does not directly lower platelets, except in the presence of heparin-induced thrombocytopenia (HIT). (Choice E) Tranexamic acid (Cyklokapron, Lysteda) is an antifibrinolytic drug used to induce hemostasis. The oral formulation Lysteda is used to stop menorrhagia. Tranexamic acid's mechanism of action stops the breakdown of blood clots and does not impact heparin. Things to remember:Protamine sulfate rapidly neutralizes the anticoagulation effects of unfractionated heparin and partially reverses the effects of low molecular weight heparin.

PR is a 76-year-old female who reports occasional episodes of dizziness and a racing heartbeat after her evening walks over the past few weeks. An electrocardiogram reveals an "irregularly irregular" heart rate and rhythm. She is subsequently diagnosed with nonvalvular atrial fibrillation. There are no other significant laboratory or physical examination findings. Past Medical History: hypertension, hypothyroidism Social History: smokes cigarettes (1 cigarette after dinner), does not drink alcohol Allergies: none Medications: levothyroxine 25 mcg PO QAM, Lotrel 10/20 mg PO QAM Vital Signs: BP 132/82 mmHg, HR 96 bpm, Ht 64″, Wt 130 lbs Which of the following medications should be added to the patient's regimen?

D. Rivaroxaban In atrial fibrillation (AF), disorganized atrial contractions can lead to blood stasis and clot formation. Patients with AF have a five-fold increased risk of thromboembolism (including stroke). Oral anticoagulation reduces stroke risk, estimated by the CHA2DS2-VASc score, in some nonvalvular AF patients. The HAS-BLED score calculates the risk of major bleeding and can identify patients who require more frequent monitoring when anticoagulated. This patient's CHA2DS2-VASc score is 4 [female (+1), hypertension (+1), older than 75 (+2)], placing her in a high stroke risk category. Females with a score of ≥ 3 require anticoagulation, preferably with a direct-acting oral anticoagulant (DOAC) [eg, apixaban (Eliquis), rivaroxaban (Xarelto)] due to a more favorable risk-benefit profile compared to warfarin (eg, similar efficacy, decreased risk of intracranial hemorrhage). (Choices A and B) Antiplatelet therapy [eg, aspirin/dipyridamole (Aggrenox), clopidogrel (Plavix)], as dual or monotherapy, is inferior to oral anticoagulation for stroke prevention and should be considered only if contraindications (ie, allergy) exist to both warfarin and DOACs. (Choice C) Nimodipine, a dihydropyridine calcium channel blocker, reduces cerebral vasospastic activity in patients experiencing acute subarachnoid hemorrhage. It has an affinity for the cerebral arteries and should not be used in the management of hypertension. (Choice E) Warfarin (INR goal of 2-3) can be used for stroke prophylaxis in patients with AF but is less desirable than DOACs because of the increased risk of bleeding and the need for frequent monitoring. Warfarin is the preferred treatment for valvular AF. Things to remember:Patients with atrial fibrillation and a higher risk for stroke (as determined by CHA2DS2-VASc score) should be anticoagulated, preferrably with a direct-acting oral anticoagulant.

A 76-year-old female with longstanding atrial fibrillation comes to the clinic for an appointment 3 months after hospitalization for atrial fibrillation with rapid ventricular response. While hospitalized, the patient was started on amiodarone, and the dose of metoprolol was increased. Past Medical History: atrial fibrillation, dyslipidemia, hypertension, ischemic stroke Home Medications:Amiodarone 200 mg PO dailyAspirin 81 mg PO dailyLisinopril 20 mg PO dailyMetoprolol tartrate 50 mg PO BIDRosuvastatin 20 mg PO HSWarfarin 2 mg PO daily Vital Signs: BP 103/65 mmHg, HR 45 bpm, RR 16 bpm, Ht 5' 6", Wt 63 kg Laboratory Tests:Serum creatinine 1.8 mg/dLINR 2.2 Diagnostic Tests:Electrocardiogram: normal sinus rhythm The prescriber discontinues amiodarone. What is the expected impact of the medication change on the patient's anticoagulation?

D. The INR will decrease and the patient may clot Warfarin (Coumadin, Jantoven) is a racemic mixture of R- and S-warfarin, with S-warfarin being the more potent enantiomer. R- and S-warfarin are oxidatively metabolized by different CYP450 enzymes in the liver to inactive metabolites. S-warfarin is metabolized by CYP2C9 and R-warfarin by CYP1A2, 2C19, and 3A4. Initiation or discontinuation of drugs that impact these CYP enzymes alter the anticoagulant effect of warfarin. Inhibition of warfarin metabolism leads to higher warfarin serum levels and, ultimately, an increased INR and risk of bleeding. Amiodarone (Pacerone, Nexterone) (an antiarrhythmic) inhibits CYP2C9, 3A4, and 2D6. When initiating amiodarone in a patient stabilized on warfarin, the reduction in warfarin metabolism results in an increased INR. To reduce the risk of a supratherapeutic INR and bleeding, the dose of warfarin is often decreased by 30 to 50%. If amiodarone is discontinued, the inhibition of warfarin metabolism by amiodarone slowly decreases (over several months). Therefore, the INR must be monitored, and the dose of warfarin will need to be increased to reduce the risk of clotting due to inadequate anticoagulation. (Choice A) The INR will decrease when amiodarone is discontinued, which increases the risk of clotting, not bleeding. (Choices B and C) Following discontinuation of amiodarone, the INR will decrease (not increase), which increases the risk of clotting. In comparison, when amiodarone is initiated, the INR will increase, which can result in bleeding (not clotting). Things to remember:Amiodarone's inhibition of CYP450 2C9 and 3A4 leads to an increased anticoagulant effect from warfarin (increased INR). Discontinuation of amiodarone in a patient stabilized on warfarin results in a decreased anticoagulant effect (decreased INR) as the effects of amiodarone wear off.

Select the incorrect statement about Pradaxa.

D. The effect can be reversed with Mephyton Dabigatran (Pradaxa) is formulated as a capsule. The capsules must be swallowed whole; do not open and administer via an NG tube. Phytonadione (Mephyton) is the antidote for warfarin. The antidote for dabigatran is idarucizumab (Praxbind).

The pharmacist is paged to review a critical laboratory result. Laboratory Tests:Prothrombin time 17 secActivated partial thromboplastin time > 150 secPlasma fibrinogen 220 mg/dLINR 1.2 Which of the following medications should be adjusted based on these results?

D. Unfractionated heparin Anticoagulants are high-riskmedications that must be monitored closely for safety and efficacy. In general, medications that affect the extrinsic pathway prolong the prothrombin time (PT), whereas inhibition of the intrinsic pathway prolongs the activated partial thromboplastin time (aPTT). Medications that affect the final common pathway (factor X or factor II) can prolong the aPTT or PT. Thrombin time (TT) is prolonged by medications that directly or indirectly inhibit thrombin. Unfractionated heparin (UFH) acts via antithrombin-associated inhibition of factors X and II; UFH should prolong both PT and PTT. However, the commonly used PT reagents contain heparin-binding chemicals (eg, heparinase, polybrene) that block this PT prolongation effect. Therefore, PT is usually reported as normal for patients receiving UFH. The aPTT is the most common monitoring parameter for UFH and evaluates blood clotting time (in seconds). The higher the aPTT, the more anticoagulated the patient is. UFH can also be monitored by anti-Xa levels in select patients or institutions. (Choice A) Cangrelor is an intravenous antiplatelet medication used in patients unable to take an oral P2Y12 inhibitor. Platelet function activity can be monitored using specialized tests, but these are not routinely recommended. (Choice B) Dabigatran, an oral direct thrombin inhibitor (DTI), is not routinely monitored for efficacy with any laboratory test. Intravenous DTIs (argatroban and bivalirudin) also prolong both PT/INR and aPTT. The aPTT is the monitoring parameter of choice for IV DTIs because the effect of the PT varies by drug and reagent used. (Choice C) Factor Xa inhibitors (eg, rivaroxaban) are not routinely monitored for efficacy. Specialized anti-Xa testing can be performed in certain circumstances. (Choice E) Warfarin is monitored by PT/INR because its effect is mainly on the extrinsic pathway (factor VII). Things to remember:Many anticoagulants require laboratory monitoring to ensure safe, effective therapy and reduce the risk of bleeding. Unfractionated heparin is routinely monitored with activated partial thromboplastin time.

BW is a 25-year-old female with antiphospholipid syndrome admitted for a pulmonary embolism. She was started on warfarin (goal INR: 2.0-3.0) plus enoxaparin on June 24th. Enoxaparin was discontinued on July 1st at the time of hospital discharge. Date Warfarin Dose INR 6/24 10 mg 1.4 6/25 5 mg 1.6 6/26 5 mg 1.7 6/27 5 mg 2.0 6/28 5 mg 1.8 6/29 5 mg2.2 6/30 5 mg 2.4 7/1 5 mg 2.3 On which date should enoxaparin have been discontinued?

E. 6/30 Warfarin is an inhibitor of the vitamin K epoxide reductase enzyme complex (VKORC1). It stops the formation of new active vitamin K-dependent clotting factors (VII, IX, X, and II) and two natural anticoagulants (protein C and protein S). Warfarin does not inhibit existing clotting factors. The onset of anticoagulation depends on elimination of the existing clotting factors according to their half-lives. The INR increases after 1-2 days due to the short half-life of factor VII, but therapeutic anticoagulation does not occur for several days due to the long half-life of factor II (60 hours). Patients are prothrombotic early in warfarin therapy because proteins C and S are depleted before clotting factors X and II. Warfarin must be used with a rapid-acting parenteral anticoagulant (eg, enoxaparin) when treating a venous thromboembolism (Choice A). The overlap period with a parenteral anticoagulant and warfarin is commonly referred to as "bridging." The bridging period must last: A minimum of 5 days AND Until the INR is therapeutic for at least 24 hours (Choice B) It is too early to discontinue enoxaparin on day 4 of therapy despite the INR being therapeutic; there is still an increased risk of clotting. In addition, the INR has not been therapeutic (at least 2.0) for at least 24 hours. (Choice D) The patient has been bridged for 6 days and the INR is therapeutic; however, the INR has not been therapeutic for at least 24 hours. Things to remember:Warfarin has a slow onset of therapeutic anticoagulant activity. It must be used with a parenteral anticoagulant for at least 5 days and until the INR is therapeutic for at least 24 hours.

Chief Complaint: "I feel dizzy." History of Present Illness: GH is an 84-year-old male patient with a long history of cardiovascular disease. He has been feeling dizzy when walking, but otherwise reports that he is doing well. His PCP did an ECG in the office today and GH was found to be in atrial fibrillation. Allergies: sulfa Past Medical History: Hypertension, MI x 2 (25 and 12 years ago - no stents), heart failure (last ECHO: EF 29%), type 2 diabetes, osteoarthritis Medications: Mobic 7.5 mg daily, Coreg 6.25 mg BID, Zestril 10 mg daily, Lasix 40 mg daily, Lantus 7 units at HS, Glucophage XR 1,000 mg daily, aspirin 81 mg daily Physical Exam / Vitals: Height: 5'7" Weight: 152 lbs Vitals: BP: 145/89 HR: 98 BPM RR: 14 BPM Temp: 98.8 F O2 Sat: 97% Pain: 2/10 General: Elderly male accompanied by daughter Cardiovascular: Irregularly irregular Lungs: Crackles bilaterally L worse than R Extremities: 1+ pitting edema bilaterally. No infection or lesions of the extremities. Labs: Na (mEq/L) = 135 (135 - 145) WBC (cells/mm3) = 6.3 (4 - 11 x 103) K (mEq/L) = 3.5 (3.5 - 5) Hgb (g/dL) = 16.2 (13.5 - 18 male, 12 - 16 female) Cl (mEq/L) = 100 (95 - 103) Hct (%) = 48 (38 - 50 male, 36 - 46 female) HCO3 (mEq/L) = 26 (24 - 30) Plt (cells/mm3) = 246 (150 - 450 x 103) BUN (mg/dL) = 22 (7 - 20) AST (IU/L) = 12 (10 - 40) SCr (mg/dL) = 1.4 (0.6 - 1.3) ALT (IU/L) = 23 (10 - 40) Glucose (mg/dL) = 188 (100 - 125) Albumin (g/dL) = 2.9 (3.5 - 5) Ca (mg/dL) = 8.7 (8.5 - 10.5) A1C (%) = 8.7 Mg (mEq/L) = 1.9 (1.3 - 2.1) PT (sec) = 12 (10 - 13) PO4 (mg/dL) = 2.5 (2.3 - 4.7) INR = 1 Tests:CXR: Cardiomegaly, hazy infiltrates bilaterallyECG: Atrial fibrillation Plan: Refer to the hospital for management of new onset atrial fibrillation.

E. CHA2DS2-VASc score = 6; oral anticoagulation is recommended The CHA2DS2-VASc incorporates a few additional stroke risk factors as compared to CHADS2, which was used previously. Oral anticoagulation is recommended when the score is ≥ 2 in males and ≥ 3 in females.

A 24-year-old female, gravida 1 para 0, at 16 weeks of gestation comes to the emergency department due to swelling and pain in her left leg. On physical examination, the left calf is larger than the right and tender to palpation. Left lower leg ultrasound reveals a deep vein thrombosis. The patient is given a drug that potentiates antithrombin. What drug did the patient receive?

E. Enoxaparin The patient has a deep vein thrombosis (DVT) that was likely precipitated by pregnancy, a risk factor for venous thromboembolism. Blood clots during pregnancy are safely treated with unfractionated heparin (UFH) or low molecular weight heparins (LMWHs). Antithrombin, one of the body's natural anticoagulants, binds to factors Xa and IIa (thrombin) in the clotting cascade to inhibit their effects. Heparins [UFH and LMWHs (enoxaparin, dalteparin)] have oligosaccharide chains containing a specific pentasaccharide sequence that binds to antithrombin, thereby causing a conformational change. This potentiates (enhances) the anticoagulant effects of antithrombin by increasing the ability to inactivate factor Xa. Only UFH has a chain long enough (> 18 saccharide units) to bind to both antithrombin and thrombin. The LMWH chain varies in length but is often shorter than UFH. As a result, UFH has equal activity against factor Xa and thrombin, whereas LMWHs have greater activity against factor Xa than thrombin. (Choice A) Alteplase (Activase) is a recombinant tissue plasminogen activator (tPA) approved for the treatment of ischemic stroke, massive pulmonary embolism, and ST-segment elevation myocardial infarction (STEMI). Alteplase converts plasminogen to plasmin, triggering the breakdown of fibrin in blood clots (ie, fibrinolysis). (Choice B) Apixaban (Eliquis) directly inhibits factor Xa. (Choices C and D) Bivalirudin (Angiomax) and dabigatran (Pradaxa) are direct thrombin inhibitors that bind to and inhibit circulating and clot-bound thrombin. Things to remember:Low molecular weight heparins and unfractionated heparin bind to antithrombin and potentiate its activity against clotting factor Xa. The longer unfractionated heparin molecule has equal activity against thrombin, whereas low molecular weight heparins have greater activity against factor Xa than thrombin.

SN is a 52-year-old female being seen in the Anticoagulation Clinic. Allergies: sulfa Past Medical History: hypertension, heart failure (last ECHO: EF 30%), lower extremity DVT (diagnosed 2 weeks ago). Medications: Coreg 6.25 mg BID, Zestril 10 mg daily, Lasix 40 mg daily, warfarin 5 mg daily Physical Exam / Vitals: Height: 5'7" Weight: 132 lbs Vitals: BP: 143/80 HR: 80 BPM RR: 14 BPM Temp: 98.8°F Labs:Na (mEq/L) = 130 (135 - 145) K (mEq/L) = 3.3 (3.5 - 5) Cl (mEq/L) = 100 (95 - 103) HCO3 (mEq/L) = 26 (24 - 30) BUN (mg/dL) = 22 (7 - 20) SCr (mg/dL) = 1.5 (0.6 - 1.3) Glucose (mg/dL) = 188 (100 - 125) Ca (mg/dL) = 8.3 (8.5 - 10.5) Mg (mEq/L) = 1.9 (1.3 - 2.1) PO4 (mg/dL) = 2.5 (2.3 - 4.7) Hgb (g/dL) = 9.1 (12 - 16 female) Hct (%) = 28.5 (36 - 46 female) Plt (cells/mm3) = 246 (150 - 450 x 103) AST (IU/L) = 12 (10 - 40) ALT (IU/L) = 23 (10 - 40) Albumin (g/dL) = 2.1 (3.5 - 5) PT (sec) = 14 (10 - 13) INR = 2.8 A1C (%) = 7.9 Question: Which of SN's lab results suggests that she could experience an altered response to warfarin?

E. Hypoalbuminemia Warfarin is highly protein-bound. Patients with low albumin (possibly malnourished) will have more free drug in their system and will be at increased risk of bleeding (especially if other risks are present). These patients generally require a lower dose. Monitor carefully.

A 53-year-old female arrives at the emergency department with a severe headache, vomiting, and muscle weakness. She is found to have a right hemisphere hemorrhagic stroke. Past Medical History: hypertension, obesity Vital Signs: BP 185/105 mmHg, HR 110 bpm, RR 24 bpm, O2 sat 90% on room air, T 100.4°F (38°C), Ht 5'9", Wt 130 kg Laboratory Tests:Hemoglobin 12 g/dLHematocrit 36%Platelets 200,000 cells/mm3Serum creatinine 1.4 mg/dL What is the best option to prevent a deep vein thrombosis in this patient during the initial period of hospitalization?

E. Intermittent pneumatic compression devices Pharmacists evaluate hospitalized patients on the need for venous thromboembolism (VTE) prophylaxis. Hospital-acquired VTEs, including deep vein thrombosis (DVT) and pulmonary embolism (PE), are preventable and can occur in up to 15% of patients within the first 30 days following an acute stroke (ischemic or hemorrhagic), with the peak incidence occurring in 2-7 days. Pharmacologic DVT prophylaxis is contraindicated immediately following a hemorrhagic stroke due to the risk of exacerbating the bleed. However, nonpharmacological DVT prophylaxis can be initiated immediately with intermittent pneumatic compression (IPC) devices, sometimes called sequential compression devices (SCDs). IPC devices are sleeves or boots worn over the legs that increase blood flow by periodically filling with air to apply pressure on the legs. Initiating IPC devices within 72 hours of an acute stroke can prevent DVT. (Choice A) Aspirin is an antiplatelet drug that is started within 48 hours following an ischemic stroke for secondary stroke prophylaxis. Aspirin monotherapy is not adequate to prevent DVT. (Choices B, C, and D) Pharmacologic DVT prophylaxis with subcutaneous (SC) low molecular weight heparin (LMWH) or unfractionated heparin is considered in a stable patient 1-4 days following hemorrhagic stroke. The following doses are appropriate for DVT prophylaxis in this patient: Heparin 5,000 units SC every 8-12 hours Enoxaparin (Lovenox) 40 mg SC every 24 hours Things to remember:Pharmacologic deep vein thrombosis prophylaxis is contraindicated in patients with a life-threatening bleed. Intermittent pneumatic compression devices should be started within 72 hours of a hemorrhagic stroke to prevent deep vein thrombosis.

Which of the following anticoagulants can be used to treat patients with prosthetic heart valves?

E. Jantoven DOACs should not be used for patients with prosthetic heart valves. Only warfarin (Jantoven) is used for treating these patients.

(same as above) ST's healthcare provider would like to start warfarin per the Anticoagulation Management protocol at the hospital. Which of the following is appropriate to start along with warfarin on day #1 of therapy for the DVT?

E. Lovenox 90 mg SC q12h

KD is a 40-year-old female who presents with a new fluttering feeling in her chest after drinking a glass of wine. Her blood pressure is 118/78 mmHg. A 12-lead electrocardiogram shows that she is in atrial fibrillation with a heart rate of 92 beats per minute, and an echocardiogram shows normal left ventricular function and no valvular abnormalities. Thyroid function tests and serum creatinine are within normal limits. Which of the following medications should be started for the prevention of a stroke given her new diagnosis of atrial fibrillation?

E. No additional therapy is needed Atrial fibrillation can occur due to a reversible cause (eg, sepsis, alcohol use) or irreversible structural heart changes (eg, hypertension, valve disease). The loss of organized atrial contraction in atrial fibrillation increases the chance of stagnant blood coagulating (eg, forming of a clot) within the atria. If dislodged, the clot can travel to the brain causing a cardioembolic stroke. Anticoagulation is used to prevent strokes in patients at high risk. The CHA2DS2-VASc score assesses the likelihood of stroke based on risk factors and guides decision making on the need for anticoagulation. The risk of stroke must outweigh the risk of bleeding from anticoagulation to warrant anticoagulant therapy. Females receive one point regardless of other risk factors because they are more likely to have a stroke than a male with the same risk factors, especially when at least two non-sex risk factors are present. This female patient has a CHA2DS2-VASc score of 1 (low risk of stroke) and does not require anticoagulation. Oral anticoagulation is recommended for all patients with two or more non-sex risk factors (eg, a male with a CHA2DS2-VASc ≥ 2 or a female with a CHA2DS2-VASc ≥ 3) (Choices A and D). (Choice B) Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (eg, clopidogrel) is not recommended for the prevention of stroke in patients with atrial fibrillation. (Choice C) Ivabradine is not effective for heart rate control in patients with atrial fibrillation because it only slows electrical impulses through the sinoatrial node. It is used to reduce hospitalizations in patients with heart failure. Things to remember:The risk of bleeding associated with anticoagulation is greater than the risk of stroke in most males with a CHA2DS2-VASc score of 0 and females with a CHA2DS2-VASc score of 1.

MG is a 43-year-old male with an appointment at the anticoagulation clinic. He is usually well controlled on a warfarin regimen of 7.5 mg five days per week (Sunday, Monday, Wednesday, Friday, Saturday) and 5 mg two days per week (Tuesday, Thursday). He reports that he completed a 10-day course of levofloxacin for an upper respiratory infection this morning. His INR is elevated today at 3.5 (goal INR 2-3). He has no noticeable bleeding. In addition to holding warfarin, which of the following is the most appropriate treatment?

E. No additional therapy is required It is crucial to identify the cause of a supratherapeutic INR in a patient on warfarin and monitor for bleeding. An elevated INR can occur from drug interactions, dosing errors, acute illness, variations in vitamin K intake, heart failure, and liver disease. This patient does not have evidence of bleeding (eg, epistaxis, coffee-ground emesis, hematuria, black tarry stool, low hemoglobin/hematocrit), and the elevated INR is likely due to recent levofloxacin use (destruction of vitamin K-producing bacteria in the gut). In the absence of bleeding or minimal bleeding, a patient with a supratherapeutic INR < 4.5 can be treated by holding 1-2 doses of warfarin, monitoring the INR, and resuming warfarin when the INR is in the therapeutic range. A reduction in warfarin dose may not be necessary. (Choices A and D) IV phytonadione and 4-factor prothrombin complex concentrate are given together to treat major bleeding caused by warfarin. This combination will completely reverse anticoagulation and increase the risk of future thromboembolic events until therapeutic anticoagulation is reestablished. (Choice B) Oral phytonadione 2.5 mg can be given to patients with an INR of 4.5-10 at an increased risk of bleeding (eg, older age) and patients with an INR > 10 without bleeding. (Choice C) IM phytonadione can be administered to pediatric patients to treat/prevent vitamin K deficiency. IM administration is avoided in adults due to the risk of hematoma. Things to remember:Patients on warfarin with a supratherapeutic INR < 4.5 and no major bleeding usually have 1-2 doses of warfarin held. Warfarin can be resumed at the same or a slightly reduced dose.

A 45-year-old male is starting Xarelto for an acute deep vein thrombosis of the left lower extremity. Which of the following medications should be started on day 1 along with Xarelto?

E. No other medication is required Rapid therapeutic anticoagulation is necessary in patients with an active blood clot to prevent expansion or dislodgment. Direct-acting oral anticoagulants (DOACs) (eg, factor Xa inhibitors, direct thrombin inhibitor) provide rapid systemic anticoagulation that closely correlates with peak plasma concentration. As a result, the DOACs rivaroxaban (Xarelto) and apixaban (Eliquis) do not require overlap with another anticoagulant when initiating therapy. Although edoxaban (Savaysa) and dabigatran (Pradaxa) provide rapid systemic anticoagulation, their FDA-approved dosing regimens for treating a venous thromboembolism (VTE) require at least five days of parenteral anticoagulant administration before starting oral therapy. (Choice A) Aspirin rapidly inhibits platelet function and is used for secondary prevention of atherosclerotic cardiovascular disease (eg, ischemic stroke, myocardial infarction). Aspirin does not provide adequate anticoagulation to treat a blood clot. (Choices B and C) The parenteral drugs enoxaparin (Lovenox) and fondaparinux (Arixtra) can be used alone for rapid anticoagulation or overlapped with warfarin. This is commonly called "bridging." (Choice D) Warfarin (Coumadin, Jantoven), a vitamin K antagonist, has a delayed systemic anticoagulant effect; therefore, bridging with a parenteral drug (eg, enoxaparin, unfractionated heparin, fondaparinux) is necessary for VTE treatment. The combination of warfarin and a DOAC is not recommended because it can cause life-threatening bleeding without potential benefit. Things to remember:Unlike warfarin, direct-acting oral anticoagulants such as rivaroxaban or apixaban (factor Xa inhibitors) have a rapid onset of therapeutic anticoagulation and do not require overlap with another anticoagulant.

LL is a 27-year-old female seen in clinic for 3 weeks of general malaise, decrease in appetite, and intermittent vomiting. Past Medical History: antiphospholipid syndrome, hypothyroidism, pulmonary embolism (2 years ago) Home Medications: levothyroxine 75 mcg PO QAM, warfarin 7.5 mg PO daily Laboratory Tests:Hemoglobin 15 g/dLPlatelets 320,000/mm3Creatinine 0.9 mg/dLINR 3.4Beta-hCG positive Diagnostic Tests:Ultrasound (transvaginal): + pregnancy (estimated 8 weeks gestational age) Which of the following is the most appropriate action to take regarding LL's warfarin therapy?

E. Stop warfarin and start enoxaparin when her INR is less than 2.0 Both warfarin and heparins [unfractionated heparin and low molecular weight heparin (LMWH)] are appropriate anticoagulants for the treatment of a venous thromboembolism. However, warfarin is generally contraindicated during pregnancy because it is a small molecule (low molecular weight) that easily crosses the placenta into fetal circulation. It is considered teratogenic because fetal exposure can cause warfarin embryopathy (eg, nasal and limb hypoplasia, fetal bleeding). The risk of teratogenicity is greater during the first trimester (when significant embryonic and fetal development occurs) and with larger doses of warfarin. Low molecular weight heparins (eg, enoxaparin) are the anticoagulant of choice during pregnancy for most conditions (eg, DVT, PE) that require therapeutic anticoagulation. However, for patients with mechanical heart valves, the decision to change to LMWH depends on the risk-benefit ratio. The benefit of continuing warfarin despite its teratogenic potential may outweigh the risk of switching to a LMWH during pregnancy in patients with a mechanical heart valve requiring < 5 mg/day of warfarin. For patients with a mechanical heart valve and in the first trimester of pregnancy requiring ≥ 5 mg/day of warfarin, LMWH is recommended. (Choices A and D) Enoxaparin is the preferred anticoagulant given this patient's indication for anticoagulation (pulmonary embolism with antiphospholipid syndrome) and pregnancy (positive urine beta-hCG and transvaginal ultrasound). (Choices B and C) If the patient were not pregnant and were to be continued on warfarin, she would require a total weekly dose decrease since her INR is above the target range of 2-3. Things to remember:Warfarin crosses the placenta and can produce teratogenic effects (eg, fetal nasal and limb hypoplasia, fetal bleeding). Low molecular weight heparins (eg, enoxaparin) are the preferred anticoagulants during pregnancy.

A 41-year-old female is brought to the emergency department on July 1 due to confusion and right-sided weakness. Past Medical History: asthma, breast cancer (diagnosed 2 years ago), chronic kidney disease, depression, diabetes mellitus, migraines Home Medications: Last FillRxMedicationN/AN/AMirena IUD inserted in clinic on 4/16/15RefillLiraglutide 0.6 mg SC daily6/15RefillLisinopril 20 mg PO daily6/15RefillMetformin 500 mg PO BID6/15RefillSertraline 150 mg PO daily6/15RefillSymbicort 80/4.5 1 inhalation twice daily and as needed for shortness of breath6/15RefillTamoxifen 20 mg PO daily6/24NewDepakote ER 500 mg PO at bedtime Vital Signs: BP 188/98 mmHg, HR 88 bpm, RR 16 bpm Laboratory Tests:White blood cells 13,000 cells/mm3Hemoglobin 13 g/dLSodium 134 mEq/LPotassium 3.8 mEq/LChloride 98 mEq/LBicarbonate 19 mEq/LBlood urea nitrogen 35 mg/dLSerum creatinine 1.8 mg/dLGlucose 70 mg/dL Diagnostic Tests:CT head: basal ganglia lacunar ischemic stroke Which of the following home medications most likely contributed to the patient's new diagnosis?

E. Tamoxifen The patient has an ischemic stroke, which can occur when blood clots block blood flow to or within the brain. Medications that are associated with provoked blood clots include erythropoiesis-stimulating agents (eg, epoetin alfa, darbepoetin alfa), estrogen-containing drugs (eg, ethinyl estradiol/drospirenone, estradiol/levonorgestrel), and selective estrogen receptor modulators (SERMs). The patient has a history of breast cancer (prothrombotic condition) and is taking tamoxifen, a SERM. There are many proposed mechanisms by which tamoxifen is thought to increase clotting, including increasing thrombin generation, decreasing antithrombin, and decreasing sensitivity to activated protein C. Although both cancer and SERMs increase the risk of clotting, the benefit of SERM treatment (treating cancer) often outweighs the risk (blood clots). (Choice A) Short-term use of divalproex (Depakote, Depakote ER, Depakote Sprinkle) is not associated with blood clots; however, long-term use can lead to metabolic syndrome, which can increase the risk of a stroke. (Choice B) Liraglutide (Victoza, Saxenda) is a GLP-1 agonist that decreases (not increases) the risk of stroke in patients with diabetes. Liraglutide can cause hypoglycemia, which can mimic a stroke (confusion, coma). (Choice C) Estrogen-containing contraceptives are associated with clotting, but progestin-only intrauterine devices, such as levonorgestrel (Mirena), are not associated with an increased risk of clotting. (Choice D) Sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), can increase bleeding by inhibiting the reuptake of serotonin into platelets. Depletion of platelet serotonin reduces the ability to form a clot. Things to remember:Certain drugs (eg, erythropoiesis-stimulating agents, estrogen-containing drugs, selective estrogen receptor modulators) are associated with provoked blood clots, but the benefit to treatment initiation may outweigh the risk.

While reviewing a patient's chart, the pharmacist sees the following note:"Send tests for VKORC1 and CYP2C9 alleles"Which medication do these tests relate to?

E. Warfarin Pharmacogenomic testing for warfarin is available, but not routinely performed. Presence of the CYP 2C9*2 or *3 alleles and/or polymorphism of the VKORC1 gene can increase bleeding risk.