Properties of Oral Anticoagulants. Dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut)

Size: px
Start display at page:

Download "Properties of Oral Anticoagulants. Dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut)"

Transcription

1 Novel Oral Anticoagulants Efficacy, Laboratory Measurement, and Approaches to Emergent Reversal Warfarin, the most commonly used of the vitamin K antagonists, has been a mainstay of oral anticoagulation for decades. However, its usage is limited by morbidity and mortality secondary to bleeding as well as a cumbersome therapeutic monitoring process. In the past several years, a number of competing novel oral anticoagulants (NOACs) have been developed, each of which aspires to match or exceed warfarin s effectiveness while mitigating bleeding risk and eliminating therapeutic monitoring requirements. At present, 1 oral direct thrombin inhibitor and 2 direct factor Xa inhibitors are approved by the US Food and Drug Administration. Here, we compare the clinical efficacy and safety profiles of these new drugs. In addition, we discuss various laboratory assays that may be useful to measure these drugs in certain clinical circumstances. Finally, we discuss emerging strategies to reverse these agents in an emergency. The purpose of this article is to provide a framework for practicing pathologists to advise clinicians on NOAC laboratory measurement and management of NOAC-associated bleeding. (Arch Pathol Lab Med. 2015;139: ; doi: / arpa rs) Warfarin, the most commonly used vitamin K antagonist (VKA) in the United States, is approved by the US Food and Drug Administration (FDA) for treatment and prophylaxis of venous thromboembolism, thrombotic events in patients with atrial fibrillation and/or cardiac valve replacement, and for the reduction in risk of thromboembolic events after myocardial infarction. 1 Unfortunately, owing to a narrow therapeutic window and known interaction with various foods, bleeding events are frequently reported in patients taking warfarin. 2,3 This has led to the search for novel oral anticoagulants (NOACs) that offer equivalent or improved therapeutic profiles compared to warfarin, ideally with less bleeding risk, no interactions with food, and no FDA requirements for routine laboratory monitoring. At present, there are 3 NOACs available in the Accepted for publication March 24, From the Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut. The authors have no relevant financial interest in the products or companies described in this article. Reprints: Christopher Tormey, MD, Department of Laboratory Medicine, Yale University School of Medicine, VA Connecticut Healthcare System, 330 Cedar St, PO Box , New Haven, CT ( christopher.tormey@yale.edu). Eric Gehrie, MD; Christopher Tormey, MD United States: dabigatran etexilate (dabigatran; Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut); rivaroxaban, (Xarelto, Janssen Pharmaceuticals, Titusville, New Jersey); and apixaban (Eliquis, Bristol-Myers Squibb,. Dabigatran is a direct thrombin inhibitor that is currently FDA approved to reduce stroke and systemic embolism risk for patients with nonvalvular atrial fibrillation. 4 Rivaroxaban and apixaban are direct factor Xa inhibitors that are currently FDA approved to reduce stroke and systemic embolism risk for patients with nonvalvular atrial fibrillation. 5,6 Rivaroxaban is also currently FDA approved for the treatment of deep vein thrombosis (DVT) and pulmonary embolism and to reduce recurrence of DVT and pulmonary embolism and for DVT prophylaxis in patients undergoing knee or hip replacement surgery. 5 It is estimated that the cost of NOACs may exceed 60 times the cost of warfarin. 7 However, the NOACs have no known interactions with food, nor do they require routine laboratory draws. Table 1 offers a summary of the properties of NOACs in comparison to warfarin. EFFICACY OF NOVEL ORAL ANTICOAGULANTS Several studies have been performed to compare the effect of NOACs to established therapies. 3 The findings of the major studies that led to the FDA approval for dabigatran, rivaroxaban, and apixaban are summarized below. Dabigatran etexilate One large, randomized trial (the Randomization Evaluation of Long-Term Anticoagulation Therapy [RE-LY]) compared 2 doses of dabigatran therapy (110 mg and 150 mg) to warfarin therapy in patients with atrial fibrillation and an increased stroke risk. 8 Both doses of dabigatran were found to be noninferior to warfarin therapy for the prevention of stroke or systemic embolism. 8 Treatment with 150 mg of dabigatran was superior to warfarin for the prevention of stroke or systemic embolism. 8 However, the rate of myocardial infarction was higher among patients taking either dose of dabigatran than patients taking warfarin. 8 While both doses of dabiagtran had lower rates of intracranial hemorrhage and life-threatening bleeding than warfarin therapy, the 150 mg dose of dabigatran was more likely than warfarin to cause major gastrointestinal bleeding. 8 Interestingly, the FDA did not approve the 110- mg dose of dabigatran, but did approve a 75-mg dose for use in patients with impaired renal function without an additional clinical trial. 9 A subsequent phase 2 dosevalidation study found that dabigatran therapy was associ- Arch Pathol Lab Med Vol 139, May 2015 Novel Oral Anticoagulants Gehrie & Tormey 687

2 Warfarin (Coumadin, Table 1. Properties of Oral Anticoagulants Dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut) Rivaroxaban (Xarelto, Janssen Pharmaceuticals Inc, Titusville, New Jersey) Apixaban (Eliquis, Class Oral VKA Oral DTI Oral factor Xa inhibitor Oral factor Xa inhibitor FDA-approved indication Boxed label warning Prophylaxis and treatment of VTE/PE; prophylaxis and treatment of thromboembolism associated with afib or heart valve; reduction in death risk or recurrent MI or thromboembolic events after MI. To reduce stroke and systemic embolism risk for patients with nonvalvular afib. Can cause major or fatal Increased risk of stroke if bleeding; perform discontinued without regular monitoring (INR) adequate continuous on patients receiving anticoagulation. treatment; drugs, dietary changes, and other factors affect INR levels; instruct patients how to prevent bleeding and to report signs or symptoms of bleeding. To reduce stroke and systemic embolism risk for patients with nonvalvular afib; for DVT and PE treatment and to reduce recurrence risk of DVT and PE; for DVT prophylaxis in patients undergoing knee or hip replacement surgery. Increased risk of stroke if discontinued without adequate continuous anticoagulation; spinal/ epidural hematoma in patients receiving neuraxial anesthesia or undergoing spinal puncture. To reduce stroke and systemic embolism risk for patients with nonvalvular afib. Increased risk of stroke if discontinued without adequate continuous anticoagulation. Half-life, h ~ h with single dose, 12 h repeated dosing Dose Adjusted to achieve target INR 75- or 150-mg tablets twice daily, depending 10-, 15-, 20-mg tablets; dosing depends on CrCl 2.5 or 5 mg twice daily, depending on age, weight, Discontinue before surgery? Consider benefits and risks on CrCl Yes a : CrCl. 50 ml/min, 1 2 d CrCl, 50 ml/min, 3 5 d and indication Yes: at least 24 h and serum Cr Yes: moderate or high risk:.48 h Low risk:.24 h Pregnancy Category D if heart Category C Category C Category B valve, otherwise X Elimination Urine Urine and feces Urine and feces Urine and feces CYP450 inhibitor, Substrate of CYP2C9, No Substrate of CYP3A4/5 inducer, or substrate? 2C19, 2C8, 2C18, 1A2, 3A4 and CYP 2J2 Substrate of CYP3A4 and 1A2, 2C8, 2C9, 2C19, 2J2 Abbreviations: afib, atrial fibrillation; Cr, creatinine; CrCl, creatinine clearance; CYP, cytochrome P; DTI, direct thrombin inhibitor; DVT, deep vein thrombosis; FDA, US Food and Drug Administration; INR, international normalized ratio; MI, myocardial infarction; PE, pulmonary embolism; VKA, vitamin K antagonist; VTE, venous thromboembolism. a For a detailed discussion of dabigatran discontinuation before surgery, please see van Ryn et al. 24 ated with a higher incidence of bleeding complications and thromboembolism than warfarin in patients with mechanical heart valves. 10 Because of this finding, dabigatran is not approved for use in patients with mechanical heart valves. 4 Rivaroxaban A large, double-blind clinical trial (ROCKET AF) comparing rivaroxaban (15 or 20 mg daily dose) to doseadjusted warfarin (target international normalized ratio [INR]: 2 3) concluded that rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation and an increased risk of stroke. 11 ROCKET AF also found that rivaroxaban therapy was associated with less intracranial hemorrhage and fewer fatal bleeds, but more major gastrointestinal bleeds, compared to warfarin therapy. 11 An open-label, randomized noninferiority study (EIN- STEIN) compared rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg daily for 3, 6, or 12 months) to the low-molecular-weight heparin enoxaparin (1 mg/kg body weight, dosed twice daily) followed by either warfarin or acenocoumarol (to achieve an INR of 2 3) for patients with acute, symptomatic DVT. 12 This study found that rivaroxaban was noninferior to enoxaparin followed by warfarin, with equivalent rates of major bleeding; however, the patients receiving VKA therapy were only found to be within the INR therapeutic range approximately 57.7% of the time. 12 A randomized, double-blind, placebo-controlled continued treatment study (EINSTEIN extension) compared rivaroxaban 20 mg daily to placebo for 6 to 12 months in patients with a history of symptomatic DVT or pulmonary embolism who had already completed 6 or 12 months of VKA or rivaroxaban therapy. 12 This trial found that rivaroxaban therapy reduced the rate of recurrent venous thromboembolism compared to placebo without increasing the risk of fatal bleeding. 12 Finally, a randomized, doubleblind clinical trial (RECORD3) comparing oral rivaroxaban (10 mg daily) to subcutaneous enoxaparin (40 mg once 688 Arch Pathol Lab Med Vol 139, May 2015 Novel Oral Anticoagulants Gehrie & Tormey

3 Table 2. Property/Drug Routine monitoring required? Qualitative assessment of NOAC levels Quantitative assessment of NOAC levels Laboratory Monitoring of US Food and Drug Administration Approved Oral Anticoagulants Warfarin (Coumadin, Dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut) Rivaroxaban (Xarelto, Janssen Pharmaceuticals Inc, Titusville, New Jersey) Yes No No No N/A aptt a,pt a,tt a PT a PT a PT/INR dtt b,eca b, ECT b Chromogenic anti factor Xa c Apixaban (Eliquis, Bristol-Meyers Squibb, Princeton, New Jersey) Chromogenic anti factor Xa c Abbreviations: aptt, activated partial thromboplastin time; dtt, dilute thrombin time; ECA, ecarin chromogenic assay; ECT, ecarin clotting time; FDA, US Food and Drug Administration; INR, international normalized ratio; N/A, not applicable; NOAC, novel oral anticoagulant; PT, prothrombin time; TT, thrombin time. a Therapeutic range has not been determined. b These assays are not FDA approved and are not routinely available. c Care must be taken to use appropriate calibrator (see text for details). daily) in patients undergoing total knee arthroplasty found that treatment with rivaroxaban provided more effective thromboprophylaxis than treatment with enoxaparin. 13 Rivaroxaban and enoxaparin therapy were associated with similar instances of major bleeding. 13 Apixaban A large, double-blind clinical trial (ARISTOTLE) comparing apixaban (5 mg twice daily) to dose-adjusted warfarin (target INR: 2 3) found that apixaban was superior to warfarin for the prevention of ischemic or hemorrhagic stroke or systemic embolism among patients at risk for stroke and with atrial fibrillation. 14 The ARISTOTLE trial also found that patients taking apixaban were less likely to suffer major or nonmajor bleeding or to die than patients taking warfarin. 14 LABORATORY MEASUREMENT OF NOVEL ORAL ANTICOAGULANTS Because VKAs have a narrow therapeutic index and various factors (including diet and genetics) influence response to therapy, patients taking VKAs are routinely monitored by using the INR. In contrast, NOACs have predictable pharmacokinetics, eliminating the need for routine laboratory assessment. As a result, NOAC-specific laboratory assays are not widely available at present. 3 6 While the lack of routine monitoring is convenient and may help to mitigate some of the costs associated with NOACs, it may be informative to measure NOAC levels in patients presenting with relatively high or low body weight, renal insufficiency (dabigatran), patients taking other medications that alter P-glycoprotein and cytochrome P3A4 metabolism, or in patient populations that were not included in NOAC clinical trials. 15 In addition, the lack of a well-characterized NOAC laboratory assay may complicate the management of cases of NOAC overdose, NOAC-associated life-threatening bleeding, or the scheduling of urgent surgery in patients taking NOACs. 16 Therefore, it is recommended that clinical laboratories have a strategy for the assessment of NOACinduced changes in coagulation. 15 In addition, clinical laboratories should be aware that depending on the drug and the methodology NOAC therapy may alter clotting factor, protein C, antithrombin, and/or fibrinogen assays performed in clinical laboratories. 15 Approaches for laboratory assessment of NOACs are discussed below and summarized in Table 2. Dabigatran etexilate Dabigatran therapy is known to prolong numerous routine laboratory assessments of hemostasis, including the activated partial thromboplastin time (aptt), the prothrombin time (PT), and the thrombin time (TT). Of these, the aptt is suggested in the dabigatran package insert. 4 However, there is no defined aptt therapeutic range for dabigatran, 4,16 and the aptt assay is relatively insensitive to different plasma concentrations of some direct thrombin inhibitors. 16,17 In addition, the aptt may not be used to assess dabigatran therapy if the patient has a lupus anticoagulant or an intrinsic clotting factor deficiency, as the aptt prolongation from these conditions will mask the effect of dabigatran on the aptt. 18 In comparison to the aptt, the TT is far more sensitive and the PT is less sensitive to dabigatran therapy. 15 Therefore, a normal aptt or TT most likely excludes therapeutic levels of dabigatran, while a normal PT may not. 15 Quantitative assessment of dabigatran levels can be obtained with the dilute thrombin time (dtt), the ecarin clotting time, or the ecarin chromogenic assay. 16 Unfortunately, at present, these assays are not generally available and do not yet have FDA approval for measuring levels of dabigatran or other direct thrombin inhibitors Some laboratories may elect to make these assays available as laboratory-developed tests. 16 Rivaroxaban and Apixaban As with dabigatran, routine assessment is not required for patients taking rivaroxaban or apixaban owing to their predictable pharmacokinetics. 5,6 At present, no assays or calibration reagents are FDA approved for the measurement of the direct oral factor Xa inhibitors, although such reagents may be available to clinical laboratories on a research use only basis. While rivaroxaban and apixaban have been shown to affect routine coagulation tests, including the aptt, activated clotting time, PT, and chromogenic anti factor Xa assay, 15,19 no therapeutic ranges exist, complicating the interpretation of the results of these tests. 19,20 Overall, studies using spiked plasma samples suggest using either the PT (for a qualitative assessment of direct oral factor Xa inhibitors) or the chromogenic anti factor Xa assay (for a quantitative assessment of direct oral factor Xa inhibitors). 15,19 21 The PT provides a relatively more sensitive assessment of rivaroxaban and apixaban than the aptt or the activated clotting time. 15,19 Authors of a study performed Arch Pathol Lab Med Vol 139, May 2015 Novel Oral Anticoagulants Gehrie & Tormey 689

4 Property/Drug Table 3. Warfarin (Coumadin, Considerations in the Emergent Reversal of Oral Anticoagulants in the Setting of Moderate to Severe Hemorrhage Dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut) Rivaroxaban (Xarelto, Janssen Pharmaceuticals Inc, Titusville, New Jersey) Apixaban (Eliquis, Blood Product Platelets No a No a No a No a FFP Yes b No a No a No a Cryoprecipitate No a No a No a No a 3-Factor PCC No Consider c,d Consider c,d Consider c,d 4-Factor PCC Yes b,e Consider d Consider d Consider d FEIBA No Consider c,d Consider c,d Consider c,d rfviia No Consider c,d Consider c,d Consider c,d Antifibrinolytics No No d No d No d Drug Removal Activated charcoal No Recommend f Recommend f Recommend f Hemodialysis No Recommend No No Other Therapy Vitamin K Yes b,e No No No Abbreviations: FEIBA, factor eight inhibitor bypass activity; FFP, fresh frozen plasma; PCC, prothrombin complex concentrate; rfviia, recombinant factor VIIa. a The use of FFP, platelets, or cryoprecipitate may be indicated owing to blood loss, but these therapies would not be expected to be helpful as monotherapy in the reversal of the novel oral anticoagulants. b Consult Guyatt et al 22 for specific recommendations. c At hospitals where 4-factor PCC is not available, the blood bank may consider using a 3-factor PCC or an activated product (FEIBA or rfviia). For details, see Winkler and Tormey. 16 Activated factors may be more thrombogenic than the 4-factor PCC. d To date, no clinical trial has been performed to assess the efficacy of this approach. e A 4-factor PCC that is intended to be administered with vitamin K was recently approved by the US Food and Drug Administration for the purpose of treating major bleeding in patients taking vitamin K antagonists. 23 f Only thought to be effective if the last dose was within 1 to 2 hours (eg, in an overdose). by the manufacturer of apixaban recommended the chromogenic anti factor Xa assay for assessment of apixaban. 21 If the chromogenic anti factor Xa assay is used, it is important to use the appropriate calibrator (and specifically not to use heparin calibrators). 15 If the PT assay is used, the performing laboratory should be aware that PT prolongation is sensitive to the thromboplastin reagent and conversion to the INR increases measurement variability. 21 POTENTIAL REVERSAL OF NOVEL ORAL ANTICOAGULANTS Vitamin K antagonists mediate their anticoagulant effect by inducing a deficiency of coagulation factors II, VII, IX, and X. Therefore, VKA reversal can be accomplished by stopping the VKA, replacing vitamin K and providing an exogenous source of vitamin K dependent clotting factors. 22 In contrast, NOACs mediate their anticoagulant effect by directly inhibiting their target coagulation factors. Accordingly, a successful strategy to reverse NOACs would require either removing the drugs from circulation or overwhelming their inhibitory effects. While a 4-factor prothrombin complex concentrate (PCC) was recently FDA approved for the reversal of warfarin in patients with acute, major bleeding, 23 no specific NOAC reversal agent (or antidote ) is available for clinical use to date. In addition, no clinical trials have been conducted to assess the efficacy of PCCs or recombinant factor VIIa (rfviia) in bleeding patients taking NOACs. 15 While NOACs have shorter half-lives than warfarin 1,4 6 and are not associated with a higher risk of bleeding, it may be necessary to attempt to reverse the effect of NOACs in cases of life-threatening bleeding, or in cases where other clinical factors are preventing timely clearance of a NOAC. Although there is insufficient evidence to formulate clear clinical guidelines, considerations in the treatment of NOACs (accumulated from case reports/series and the authors experiences) are discussed below and summarized in Table 3. Dabigatran etexilate There is no FDA-approved specific reversal agent for dabigatran and there are no clinical trials that have studied the efficacy of various interventions in bleeding patients taking dabigatran. 16 In cases where intervention beyond supportive care is deemed to be necessary (eg, lifethreatening bleeding or suspected overdose), there is limited evidence to support the use of activated charcoal therapy if the dabigatran was ingested within 1 to 2 hours. 16,24 26 In certain clinical situations, hemodialysis may be considered, as dabigatran is only 35% bound to plasma proteins and, according to the manufacturer, hemodialysis may remove 49% to 57% of dabigatran within 4 hours. 4 Several studies have been published investigating the efficacy of PCCs, rfviia, and/or fresh frozen plasma (FFP) in animal models of bleeding A murine model of dabigatran-associated bleeding found that rfviia and combinations of rfviia plus a 4-factor PCC improved the aptt, but not blood loss volume. 27 Treatment with either the combination of rfviia plus a 4-factor PCC or treatment with factor eight inhibitor bypass activity (FEIBA, an activated PCC) improved the bleeding time but had an insignificant effect on blood loss. 27 Another murine model reported that 4-factor PCC, but not rfviia, reduced expansion of intracranial hematomas. 28 In contrast, a study of dabigatran-associated bleeding in a rabbit model showed that treatment with the 4-factor PCC reduced blood loss and improved bleeding time Arch Pathol Lab Med Vol 139, May 2015 Novel Oral Anticoagulants Gehrie & Tormey

5 The applicability of these animal models to patients receiving dabigatran who experience major bleeding is uncertain. One randomized, placebo-controlled trial in healthy males treated with dabigatran showed that treatment with a 4-factor PCC did not reverse the dabigatran effect on aptt, endogenous thrombin potential lag time, TT, or the ecarin clotting time. 30 There are several case reports of patients with lifethreatening bleeding associated with dabigatran therapy with variable reported responses to intervention Many of the reports seem to indicate that treatment with FFP, rfviia, PCCs, fibrinogen, and/or platelets were not helpful in achieving clinically relevant levels of hemostasis, 31,32,34,35,37 with a few reports suggesting a benefit from rfviia, hemodialysis, or PCC therapy. 33,34,36 There is 1 report of what appears to be a dramatic response to FEIBA, but this outcome has not been confirmed by other published case reports. 38 Overall, the available information from animal models, a clinical trial in healthy young volunteers, and a series of case reports does not identify a generalizable, evidence-based strategy to achieve hemostasis in dabigatran-associated bleeding. It seems that activated charcoal therapy within 1 to 2 hours of a dose and hemodialysis are the most effective strategies, in the proper clinical context. Other therapies, such as PCCs and rfviia, may be considered in cases of lifethreatening bleeding, but the potential benefits, as well as the potential inefficacy of the therapy, should be weighed against the possibility of thrombosis on a patient-by-patient basis. At our institutions, we are consulted several times per month for recommendations to achieve reversal of dabigatran in bleeding patients. Our approach at present is to recommend drawing pretreatment laboratory tests (PT/ INR, PTT, TT, and a complete blood count) and, in the event of an overdose within the past 2 hours, the administration of activated charcoal. If the patient has mild bleeding (defined as World Health Organization [WHO] grade 1 2), we recommend supportive care and careful observation. If the patient has life-threatening bleeding (WHO grade 3 4), we recommend hemodialysis if (1) the patient s creatinine clearance is below 30 ml/min, (2) the patient has acute kidney injury, and (3) the last dose of dabigatran was more than 2 but less than 12 hours before presentation. If criteria for hemodialysis are not met, we recommend delaying/ discontinuing dabigatran, fluid support (including blood product support) as needed, and the consideration of offlabel use of 4-factor PCC (25 units/kg, dose not to exceed 2500 units). We do not recommend redosing the 4-factor PCC, nor do we recommend providing rfviia or FEIBA within 24 hours of a dose of the 4-factor PCC owing to our concern for possible thromboembolic complications. Rivaroxaban and Apixaban Similar to dabigatran, activated charcoal may prevent absorption of rivaroxaban and apixaban if administered 1 to 2 hours after ingestion. 5,6 Rivaroxaban and apixaban are highly bound to plasma proteins and therefore, unlike dabigatran, there is no role for hemodialysis in the management of bleeding associated with their use. 5,6 There is no currently available antidote for rivaroxaban or apixaban. 5,6 Notably, a promising factor Xa inhibitor reversal agent (andexanet-a) has been reported in the medical literature, tested in an animal model, and is currently undergoing clinical trials. 39 At present, however, andexaneta is not available for clinical use. Animal models have been used to study the effect of various interventions on rivaroxaban-related bleeding. One study of rivaroxaban-induced bleeding in a rabbit model reported that a 4-factor PCC and recombinant factor VIIa (rfviia) improved coagulation laboratory studies but did not significantly reduce bleeding. 40 Another study 41 showed that a 4-factor PCC, FEIBA, and rfviia improved laboratory assessments of coagulation and reduced bleeding times in rats treated with rivaroxaban. A baboon model of rivaroxaban-associated bleeding also showed potential utility of FEIBA and rfviia in rivaroxaban reversal. 41 No human clinical trials have been performed to assess the efficacy of various interventions on rivaroxaban-related bleeding. However, a randomized, placebo-controlled study of young, healthy volunteers treated with 20 mg of rivaroxaban, dosed twice daily, found that administration of a 4-factor PCC led to normalization of the PT and the endogenous thrombin potential (apixaban was not evaluated). 30 In contrast, an in vitro study using human plasma obtained from healthy donors found that rfviia was superior to a 4-factor PCC at normalizing laboratory coagulation studies. 42 Animal studies of apixaban-related bleeding are sparse. 43 One rabbit model of apixaban-related bleeding found that treatment with rfviia, 4-factor PCC, or a fibrinogen concentrate failed to reduce hepatosplenic blood loss, with fibrinogen concentrate treatment actually increasing blood loss and bleeding time. 44 At present, we are not aware of any case reports of emergent apixaban reversal. 43 Similar to dabigatran, we are periodically consulted for recommendations to achieve reversal of rivaroxaban or apixaban in bleeding patients. As with dabigatran reversal, we always recommend drawing pretreatment laboratory tests (PT/INR, PTT, and a complete blood count) and, in the event of an overdose within the past 2 hours, the administration of activated charcoal. If the patient has mild bleeding (defined as WHO grade 1 2), we recommend supportive care and careful observation. If the patient has life-threatening bleeding (WHO grade 3 4), we recommend delaying/discontinuing the drug in question, fluid support (including blood product support) as needed, and the consideration of off-label use of a one-time dose of the 4- factor PCC (25 units/kg, dose not to exceed 2500 units). As with dabigatran reversal, we do not recommend redosing the 4-factor PCC, nor do we recommend providing rfviia or FEIBA within 24 hours of a dose of the 4-factor PCC. CONCLUSION Based on data from recent clinical trials, there is reason to believe that NOACs may offer some benefits over warfarin in certain clinical circumstances. In particular, it is believed that patients may reduce the risk of thrombotic events as well as the risk of treatment-related bleeding events while avoiding therapeutic monitoring by taking NOACs instead of warfarin for certain indications. However, warfarin has been in use for decades and has the benefit of a widely available monitoring test (PT/INR) as well as several treatment options for reversal. Although it is currently believed that patients taking NOACs have fewer lifethreatening bleeding events than patients taking warfarin, the safety of NOAC therapy is undermined by a lack of informative coagulation tests for NOAC measurement and the lack of specific NOAC reversal agents. At present, it is prudent for clinical laboratories to be aware of the effect of Arch Pathol Lab Med Vol 139, May 2015 Novel Oral Anticoagulants Gehrie & Tormey 691

6 NOACs on routine coagulation assays and to develop an approach to guide testing in circumstances where there is a clinical need to measure NOAC levels. Ideally, the clinical laboratory would act as a diagnostic consultant in NOACassociated bleeding and, together with the blood bank, guide rational (if not evidence-based) treatment for patients with NOAC-associated bleeding. Clinical trials assessing various interventions in bleeding patients (such as hemodialysis, 3- or 4-factor PCCs, rfviia, antifibrinolytic therapies, or, potentially, an antidote such as andexanet-a) would be very helpful toward the development of evidence-based guidelines for NOAC reversal. References 1. Coumadin [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007;167(13): Adam SS, McDuffie JR, Ortel TL, Williams JW Jr. Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systemic review. Ann Intern Med. 2012; 157(11): Pradaxa [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals; Xarelto [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; Eliquis [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; Avorn J. The relative cost-effectiveness of anticoagulants: obvious, except for the cost and the effectiveness. Circulation. 2011;123(22): Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12): Rieffel JA. Letter by Reiffel regarding article, Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY) trial. Circulation. 2012;125(3):e Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13): Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10): EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010; 363(26): Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358(26): Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11): Baglin T. The role of the laboratory in treatment with new oral anticoagulants. J Thromb Haemost. 2013;11(suppl 1): Winkler AM, Tormey CA; Education Committee of the Academy of Clinical Laboratory Physicians and Scientists (ACLPS). Pathology consultation on monitoring direct thrombin inhibitors and overcoming their effects in bleeding patients. Am J Clin Pathol. 2013;140(5): Curvers J, van de Kerkhof D, Stroobants AK, van den Dool EJ, Scharnhorst V. Measuring direct thrombin inhibitors with routine and dedicated coagulation assays: which assay is helpful? Am J Clin Pathol. 2012;138(4): Castellone DD, Van Cott EM. Laboratory monitoring of new anticoagulants. Am J Hematol. 2010;85(3): Douxfils J, Mullier F, Loosen C, Chatelain C, Chatelain B, Dogne JM. Assessment of the impact of rivaroxaban on coagulation assays: laboratory recommendations for the monitoring of rivaroxaban and review of the literature. Thromb Res. 2012;130(6): Asmis LM, Alberio L, Angelillo-Scherrer A, et al. Rivaroxaban: quantification by anti-fxa assay and influence on coagulation tests: a study in 9 Swiss laboratories. Thromb Res. 2011;129(4): Barrett YC, Wang Z, Frost C, Shenker A. Clinical laboratory measurement of direct factor Xa inhibitors: anti-xa assay is preferable to prothrombin time assay. Thromb Haemost. 2010;104(6): Guyatt GH, Akl EA, Crowther M, et al. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl 2):7S 47S. 23. Kcentra [prescribing information]. Marburg, Germany: CSL Behring; van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate: a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6): van Ryn J, Sieger P, Kink-Eiband M, Gansser D, Clemens A. Adsorption of dabigatran etexilate in water or dabigatran in pooled human plasma by activated charcoal in vitro [abstract]. Blood. 2009;114(22): Woo JS, Kapadia N, Phanco SE, Lynch CA. Positive outcome after intentional overdose of dabigatran. J Med Toxicol. 2013;9(2): Lambourne MD, Eltringham-Smith LJ, Gataiance S, Arnold DM, Crowther MA, Sheffield WP. Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost. 2012;10(9): Zhou W, Schwarting S, Illanes S, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke. 2011;42(12): Pragst I, Zeitler SH, Doerr B, et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (beriplex P/N) in a rabbit model. J Thromb Haemost. 2012;10(9): Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124(14): Truumees E, Gaudu T, Dieterichs C, Geck M, Stokes M. Epidural hematoma and intraoperative hemorrhage in a spine trauma patient on Pradaxa (dabigatran). Spine. 2012;37(14):E863 E Garber ST, Sivakumar W, Schmidt RH. Neurosurgical complications of direct thrombin inhibitors catastrophic hemorrhage after mild traumatic brian injury in a patient receiving dabigatran. J Neurosurg. 2012;116(5): Warkentin TE, Margetts P, Connolly SJ, Lamy A, Ricci C, Eikelboom JW. Recombinant factor VIIa (rfviia) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood. 2012;119(9): Harinstein LM, Morgan JW, Russo N. Treatment of dabigatran-associated bleeding: case report and review of the literature. J Pharm Pract. 2013;26(3): Lillo-Le Louet A, Wolf M, Soufir L, et al. Life threatening bleeding in four patients with an unusual excessive response to dabigatran: implications for emergency surgery and resuscitation. Thromb Haemost. 2012;108(3): Dumkow LE, Voss JR, Peters M, Jennings DL. Reversal of dabigatraninduced bleeding with a prothrombin complex concentrate and fresh frozen plasma. Am J Health Syst Pharm. 2012;69(19): Cano EL, Miyares MA. Clinical challenges in a patient with dabigatraninduced fatal hemorrhage. Am J Geriatr Pharmacother. 2012;10(2): Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in lifethreatening bleeding occurring during cardiac ablation with factor eight inhibitor bypassing activity. Crit Care Med. 2013;41(5):e42 e Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013;19(4): Godier A, Miclot A, Le Bonniec B, et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology. 2012;116(1): Perzborn E, Gruber A, Tinel H, et al. Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates. Thromb Haemost. 2013; 110(1): Korber MK, Langer E, Ziemer S, Perzborn E, Gericke G, von Heymann C. Measurement and reversal of prophylactic and therapeutic peak levels of rivaroxaban: an in vitro study [published online ahead of print July 5, 2013]. Clin Appl Thromb Hemost. doi: / Kaatz S, Kouides PA, Garcia DA, et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(suppl 1):S141 S Martin AC, Le Bonniec B, Fischer AM, et al. Evaluation of recombinant activated factor VII, prothrombin complex concentrate, and fibrinogen concentrate to reverse apixaban in a rabbit model of bleeding and thrombosis. Int J Cardiol. 2013;168(4): Arch Pathol Lab Med Vol 139, May 2015 Novel Oral Anticoagulants Gehrie & Tormey

NEWER ANTICOAGULANTS: FOCUS ON STROKE PREVENTION IN ATRIAL FIBRILLATION AND DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM

NEWER ANTICOAGULANTS: FOCUS ON STROKE PREVENTION IN ATRIAL FIBRILLATION AND DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM NEWER ANTICOAGULANTS: FOCUS ON STROKE PREVENTION IN ATRIAL FIBRILLATION AND DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM Carol Lee, Pharm.D., Jessica C. Song, M.A., Pharm.D. INTRODUCTION For many years, warfarin

More information

Failure or significant adverse effects to all of the alternatives: Eliquis and Xarelto

Failure or significant adverse effects to all of the alternatives: Eliquis and Xarelto This policy has been developed through review of medical literature, consideration of medical necessity, generally accepted medical practice standards, and approved by the IEHP Pharmacy and Therapeutics

More information

Disclosure. Warfarin

Disclosure. Warfarin Disclosure No conflicts of interest to disclose Reversal Strategies for Novel Oral Anticoagulants Noelle de Leon, PharmD, BCPS Critical Care Pharmacist, Department of Pharmaceutical Services Assistant

More information

Speaker Disclosure. Outline. Pharmacist Objectives. Patient Case. Outline 9/4/2014

Speaker Disclosure. Outline. Pharmacist Objectives. Patient Case. Outline 9/4/2014 Speaker Disclosure Matthew K. Pitlick, Pharm.D., BCPS St. Louis College of Pharmacy/VA St. Louis HCS mpitlick@stlcop.edu Matthew K. Pitlick, Pharm.D., BCPS declares no conflicts of interest, real or apparent,

More information

DVT/PE Management with Rivaroxaban (Xarelto)

DVT/PE Management with Rivaroxaban (Xarelto) DVT/PE Management with Rivaroxaban (Xarelto) Rivaroxaban is FDA approved for the acute treatment of DVT and PE and reduction in risk of recurrence of DVT and PE. FDA approved indications: Non valvular

More information

Out with the Old and in with the New? Target Specific Anticoagulants for Atrial Fibrillation

Out with the Old and in with the New? Target Specific Anticoagulants for Atrial Fibrillation Out with the Old and in with the New? Target Specific Anticoagulants for Atrial Fibrillation Goal Statement Pharmacists and technicians will gain knowledge in the use of target specific oral anticoagulants

More information

The author has no disclosures

The author has no disclosures Mary Bradbury, PharmD, BCPS Clinical Pharmacy Specialist, Cardiac Surgery September 18, 2012 Mary.bradbury@inova.org This presentation will discuss unlabeled and investigational use of products The author

More information

Committee Approval Date: September 12, 2014 Next Review Date: September 2015

Committee Approval Date: September 12, 2014 Next Review Date: September 2015 Medication Policy Manual Policy No: dru361 Topic: Pradaxa, dabigatran Date of Origin: September 12, 2014 Committee Approval Date: September 12, 2014 Next Review Date: September 2015 Effective Date: November

More information

Comparison between New Oral Anticoagulants and Warfarin

Comparison between New Oral Anticoagulants and Warfarin Comparison between New Oral Anticoagulants and Warfarin Warfarin was the mainstay of oral anticoagulant therapy until the recent discovery of more precise targets for therapy. In recent years, several

More information

USE AND INTERPRETATION OF LABORATORY COAGULATION TESTS IN PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN)

USE AND INTERPRETATION OF LABORATORY COAGULATION TESTS IN PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN) USE AND INTERPRETATION OF LABORATORY COAGULATION TESTS IN PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN) TARGET AUDIENCE: All Canadian health care professionals:

More information

Stop the Bleeding: Management of Drug-induced Coagulopathy. Stacy A. Voils, PharmD, BCPS Critical Care Specialist, Neurosurgery

Stop the Bleeding: Management of Drug-induced Coagulopathy. Stacy A. Voils, PharmD, BCPS Critical Care Specialist, Neurosurgery Stop the Bleeding: Management of Drug-induced Coagulopathy Stacy A. Voils, PharmD, BCPS Critical Care Specialist, Neurosurgery Objectives Discuss contemporary management of warfarin reversal in patients

More information

To assist clinicians in the management of minor, major, and/or life-threatening bleeding in patients receiving new oral anticoagulants (NOACs).

To assist clinicians in the management of minor, major, and/or life-threatening bleeding in patients receiving new oral anticoagulants (NOACs). MANAGEMENT OF BLEEDING IN PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN) TARGET AUDIENCE: All Canadian health care professionals. OBJECTIVE: To assist clinicians

More information

Reversing the New Anticoagulants

Reversing the New Anticoagulants Reversing the New Anticoagulants Disclosure Susan C. Lambe, MD Assistant Clinical Professor Department of Emergency Medicine University of California, San Francisco Roadmap for today 1 Roadmap for today

More information

Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Brief Comparison of Four Agents

Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Brief Comparison of Four Agents Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Brief Comparison of Four Agents Abbreviations AF: Atrial fibrillation ARISTOTLE: Apixaban for Reduction in Stroke and Other Thromboembolic

More information

Oral anticoagulants new and old: bleeding risk and management strategies. Logan Tinsen Pharm.D. Benefis Hospitals

Oral anticoagulants new and old: bleeding risk and management strategies. Logan Tinsen Pharm.D. Benefis Hospitals Oral anticoagulants new and old: bleeding risk and management strategies Logan Tinsen Pharm.D. Benefis Hospitals Disclaimer! I am not receiving any compensation from any drug company! Any opinions I may

More information

DABIGATRAN ETEXILATE TARGET Vitamin K epoxide reductase WARFARIN RIVAROXABAN APIXABAN

DABIGATRAN ETEXILATE TARGET Vitamin K epoxide reductase WARFARIN RIVAROXABAN APIXABAN TARGET SPECIFIC ORAL ANTICOAGULANTS (TSOACs) This document is intended as a guideline only and should not replace sound clinical judgment Please refer to UNMH formulary in Lexicomp for approved use(s)

More information

5/21/2012. Perioperative Use Issues. On admission: During hospitalization:

5/21/2012. Perioperative Use Issues. On admission: During hospitalization: Dabigatran and Rivaroxaban: Challenges in the Perioperative Setting Claudia Swenson, Pharm.D., CDE, BC-ADM, FASHP Central Washington Hospital Wenatchee, WA claudia.swenson@cwhs.com Dabigatran and Rivaroxaban:

More information

Critical Bleeding Reversal Protocol

Critical Bleeding Reversal Protocol Critical Bleeding Reversal Protocol Coagulopathy, either drug related or multifactorial, is a major contributing factor to bleeding related mortality in a variety of clinical settings. Standard therapy

More information

Recommendation for the Reversal of Novel Anticoagulants in Emergent Situations

Recommendation for the Reversal of Novel Anticoagulants in Emergent Situations Lauren Edwards PharmD Candidate 2016 Truman Medical Center, Lakewood Preceptor: Dr. Melissa Gabriel June 11, 2015 Recommendation for the Reversal of Novel Anticoagulants in Emergent Situations Background

More information

Impact of new (direct) oral anticoagulants in patient blood management

Impact of new (direct) oral anticoagulants in patient blood management Impact of new (direct) oral anticoagulants in patient blood management Yulia Lin, MD, FRCPC, CTBS Transfusion Medicine & Hematology, Sunnybrook Health Sciences Centre Dept of Laboratory Medicine & Pathobiology,

More information

Warfarin and Novel Anti-Coagulants: Management Before and After the Cath Lab

Warfarin and Novel Anti-Coagulants: Management Before and After the Cath Lab Warfarin and Novel Anti-Coagulants: Management Before and After the Cath Lab Drew Baldwin, MD Virginia Mason Seattle, Washington NCVH May 28, 2015 2:30 pm I have no disclosures. Stroke risk reduction in

More information

MANAGING BLEEDING IN THE

MANAGING BLEEDING IN THE MANAGING BLEEDING IN THE SETTING OF NEW ANTICOAGULANTS: HOW DO OLD METHODS MEASURE UP? Michelle Zeller MD Clinical Hematology Fellow November 5th, 2011 A FRIDAY NIGHT ON-CALL WITH DR. B. LUD Very keen

More information

No more rat poison? New oral anticoagulants and perioperative considerations

No more rat poison? New oral anticoagulants and perioperative considerations 1 No more rat poison? New oral anticoagulants and perioperative considerations Jerrold H. Levy, MD, FAHA, FCCM Professor Department of Anesthesiology/Critical Care Duke University School of Medicine Durham,

More information

NnEeWw DdEeVvEeLlOoPpMmEeNnTtSs IiıNn OoRrAaLl AaNnTtIiıCcOoAaGgUuLlAaTtIiıOoNn AaNnDd RrEeVvEeRrSsAaLl

NnEeWw DdEeVvEeLlOoPpMmEeNnTtSs IiıNn OoRrAaLl AaNnTtIiıCcOoAaGgUuLlAaTtIiıOoNn AaNnDd RrEeVvEeRrSsAaLl NnEeWw DdEeVvEeLlOoPpMmEeNnTtSs IiıNn OoRrAaLl AaNnTtIiıCcOoAaGgUuLlAaTtIiıOoNn AaNnDd RrEeVvEeRrSsAaLl Mikele Wissing, RN June 2014 Introduction until recently, was the unrivaled medication for treatment

More information

The management of cerebral hemorrhagic complications during anticoagulant therapy

The management of cerebral hemorrhagic complications during anticoagulant therapy The management of cerebral hemorrhagic complications during anticoagulant therapy Maurizio Paciaroni Stroke Unit Division of Cardiovascular Medicine University of Perugia - Italy Perugia Stroke Registry

More information

Dabigatran (Pradaxa) Guidelines

Dabigatran (Pradaxa) Guidelines Dabigatran (Pradaxa) Guidelines Dabigatran is a new anticoagulant for reducing the risk of stroke in patients with atrial fibrillation. Dabigatran is a direct thrombin inhibitor, similar to warfarin, without

More information

Xabans Good for What Ails Ya? Brian Tiffany, MD, PhD, FACEP Dept of Emergency Medicine Chandler Regional Medical Center Mercy Gilbert Medical Center

Xabans Good for What Ails Ya? Brian Tiffany, MD, PhD, FACEP Dept of Emergency Medicine Chandler Regional Medical Center Mercy Gilbert Medical Center Xabans Good for What Ails Ya? Brian Tiffany, MD, PhD, FACEP Dept of Emergency Medicine Chandler Regional Medical Center Mercy Gilbert Medical Center DISCLOSURES No relevant financial disclosures I will

More information

48 th Annual Meeting. Non-VKA Oral Anticoagulants: Prevention & Treatment of Bleeding. Terminology. Disclosure. Public Health Impact.

48 th Annual Meeting. Non-VKA Oral Anticoagulants: Prevention & Treatment of Bleeding. Terminology. Disclosure. Public Health Impact. 48 th Annual Meeting Terminology Non-VKA Oral Anticoagulants: Prevention & Treatment of Bleeding Stacy A. Voils, PharmD, MS, BCPS Navigating the Oceans of Opportunity Target-specific oral anticoagulants

More information

How To Treat Aneuricaagulation

How To Treat Aneuricaagulation Speaker Introduction Jessica Wilhoite, PharmD, BCACP Doctor of Pharmacy: Purdue University Postgraduate Residency Training: PGY1 Pharmacy Practice St. Vincent Hospital PGY2 Ambulatory Care St. Vincent

More information

Medication Policy Manual. Topic: Eliquis, apixaban Date of Origin: July 12, 2013. Committee Approval Date: July 11, 2014 Next Review Date: July 2015

Medication Policy Manual. Topic: Eliquis, apixaban Date of Origin: July 12, 2013. Committee Approval Date: July 11, 2014 Next Review Date: July 2015 Medication Policy Manual Policy No: dru313 Topic: Eliquis, apixaban Date of Origin: July 12, 2013 Committee Approval Date: July 11, 2014 Next Review Date: July 2015 Effective Date: August 1, 2014 IMPORTANT

More information

Devang M. Desai, MD, FACC, FSCAI Chief of Interventional Cardiology Director of Cardiac Catheterization Lab St. Mary s Hospital and Regional Medical

Devang M. Desai, MD, FACC, FSCAI Chief of Interventional Cardiology Director of Cardiac Catheterization Lab St. Mary s Hospital and Regional Medical Devang M. Desai, MD, FACC, FSCAI Chief of Interventional Cardiology Director of Cardiac Catheterization Lab St. Mary s Hospital and Regional Medical Center A.Fib affects 2.2 million Americans. The lifetime

More information

NON-VITAMIN K ORAL ANTICOAGULANT REVERSAL

NON-VITAMIN K ORAL ANTICOAGULANT REVERSAL DISCLAIMER: These guidelines were prepared by the Department of Surgical Education, Orlando Regional Medical Center. They are intended to serve as a general statement regarding appropriate patient care

More information

LAMC Reversal Agent Guideline for Anticoagulants 2013. Time to resolution of hemostasis (hrs) Therapeutic Options

LAMC Reversal Agent Guideline for Anticoagulants 2013. Time to resolution of hemostasis (hrs) Therapeutic Options LAMC Reversal Agent Guideline for Anticoagulants 2013 Medication resolution of hemostasis (hrs) Intervention Administration Instructions Heparin 3-4 Protamine 1mg IV for every 100 units of heparin Slow

More information

Session 3 Topics. Argatroban. Argatroban. Drug Use and Adverse Effects. Laboratory Monitoring of Anticoagulant Therapy

Session 3 Topics. Argatroban. Argatroban. Drug Use and Adverse Effects. Laboratory Monitoring of Anticoagulant Therapy ~~Marshfield Labs Presents~~ Laboratory Monitoring of Anticoagulant Therapy Session 3 of 4 Michael J. Sanfelippo, M.S. Technical Director, Coagulation Services Session 3 Topics Direct Thrombin Inhibitors:

More information

Analyzing Clinical Trial Findings of the Efficacy and Safety Profiles of Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation

Analyzing Clinical Trial Findings of the Efficacy and Safety Profiles of Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation Analyzing Clinical Trial Findings of the Efficacy and Safety Profiles of Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation Drew Baldwin, MD Virginia Mason Seattle, Washington NCVH May 29,

More information

The 50-year Quest to Replace Warfarin: Novel Anticoagulants Define a New Era. CCRN State of the Heart 2012 June 2, 2012

The 50-year Quest to Replace Warfarin: Novel Anticoagulants Define a New Era. CCRN State of the Heart 2012 June 2, 2012 The 50-year Quest to Replace Warfarin: Novel Anticoagulants Define a New Era CCRN State of the Heart 2012 June 2, 2012 Disclosures I have I have been involved in trials of new anticoagulants and have received

More information

New Oral Anticoagulant Drugs What monitoring if any is required?

New Oral Anticoagulant Drugs What monitoring if any is required? New Oral Anticoagulant Drugs What monitoring if any is required? Michelle Williamson Supervising Scientist High Throughput Haematology Pathology Queensland PAH Laboratory Overview Background What new oral

More information

Novel Anticoagulation Agents DISCLOSURES. Objectives ATRIAL FIBRILLATION TRIALS. NOAC Comparison 6/12/2015

Novel Anticoagulation Agents DISCLOSURES. Objectives ATRIAL FIBRILLATION TRIALS. NOAC Comparison 6/12/2015 Novel Anticoagulation Agents DISCLOSURES James W. Haynes, MD Department of Family Medicine Univ of TN Health Science Center (Chattanooga) Objectives Understand mechanism of action behind the NOAC agents

More information

Prior Authorization Guideline

Prior Authorization Guideline Guideline Guideline Name Formulary Xarelto (rivaroxaban) UnitedHealthcare Community & State Approval Date 0/0/203 Revision Date 8//204 Technician Note: CPS Approval Date: /5/20; CPS Revision Date: 8/20/204

More information

New Oral Anticoagulants

New Oral Anticoagulants New Oral Anticoagulants Tracy Minichiello, MD Associate Professor of Medicine Chief, San FranciscoVA Anticoagulation and Thrombosis Service Ansell, J. Hematology Copyright 2010 American Society of Hematology.

More information

ABOUT XARELTO CLINICAL STUDIES

ABOUT XARELTO CLINICAL STUDIES ABOUT XARELTO CLINICAL STUDIES FAST FACTS Xarelto (rivaroxaban) is a novel, oral direct Factor Xa inhibitor. On September 30, 2008, the European Commission granted marketing approval for Xarelto for the

More information

Prescriber Guide. 20mg. 15mg. Simply Protecting More Patients. Simply Protecting More Patients

Prescriber Guide. 20mg. 15mg. Simply Protecting More Patients. Simply Protecting More Patients Prescriber Guide 20mg Simply Protecting More Patients 15mg Simply Protecting More Patients 1 Dear Doctor, This prescriber guide was produced by Bayer Israel in cooperation with the Ministry of Health as

More information

NON-VITAMIN K ORAL ANTICOAGULANT REVERSAL

NON-VITAMIN K ORAL ANTICOAGULANT REVERSAL DISCLAIMER: These guidelines were prepared by the Department of Surgical Education, Orlando Regional Medical Center. They are intended to serve as a general statement regarding appropriate patient care

More information

Laboratory Testing in Patients on Novel Oral Anticoagulants (NOACs)

Laboratory Testing in Patients on Novel Oral Anticoagulants (NOACs) Laboratory Testing in Patients on Novel Oral Anticoagulants (NOACs) Dr. Art Szkotak artur.szkotak@albertahealthservices.ca University of Alberta Hospital Edmonton, AB NOACs Direct Thrombin Inhibitors (DTI):

More information

The Role of the Newer Anticoagulants

The Role of the Newer Anticoagulants The Role of the Newer Anticoagulants WARFARIN = Coumadin DAGIBATRAN = Pradaxa RIVAROXABAN = Xarelto APIXABAN = Eliquis INDICATION DABIGATRAN (Pradaxa) RIVAROXABAN (Xarelto) APIXABAN (Eliquis) Stroke prevention

More information

4/9/2015. Risk Stratify Our Patients. Stroke Risk in AF: CHADS2 Scoring system JAMA 2001; 285: 2864-71

4/9/2015. Risk Stratify Our Patients. Stroke Risk in AF: CHADS2 Scoring system JAMA 2001; 285: 2864-71 Anticoagulation in the 21 st Century Adam Karpman, D.O. Saint Francis Medical Center/Oklahoma State University Medical Center Disclosures: None Atrial Fibrillation Most common arrhythmia in clinical practice.

More information

New Oral Anticoagulants

New Oral Anticoagulants Laboratory Monitoring of New Oral Anticoagulants.....What you need to know Rita Selby MD Medical Director, Coagulation Laboratories Uniersity Health Network & Sunnybrook HSC Uniersity of Toronto The 15

More information

STARTING, SWITCHING OR STOPPING NEW ORAL ANTICOAGULANTS: A Practical Approach

STARTING, SWITCHING OR STOPPING NEW ORAL ANTICOAGULANTS: A Practical Approach STARTING, SWITCHING OR STOPPING NEW ORAL ANTICOAGULANTS: A Practical Approach Jeffrey I Weitz, MD, FRCP(C), FACP Professor of Medicine and Biochemistry McMaster University Canada Research Chair in Thrombosis

More information

New anticoagulants: Monitoring or not Monitoring? Not Monitoring

New anticoagulants: Monitoring or not Monitoring? Not Monitoring The 2 nd World Congress on CONTROVERSIES IN HEMATOLOGY (COHEM) Barcelona, Spain September 6 8, 2012 New anticoagulants: Monitoring or not Monitoring? Not Monitoring Anna Falanga, MD Immunohematology and

More information

FDA Approved Oral Anticoagulants

FDA Approved Oral Anticoagulants FDA Approved Oral Anticoagulants Generic (Trade Name) Warfarin (Coumadin, Jantoven ) 1 FDA approved indication Prophylaxis and treatment of venous thromboembolism (VTE) Prophylaxis and treatment of thromboembolic

More information

New Oral Anticoagulants in the Management of Atrial Fibrillation June, 2012 By Deborah K Brokaw, Pharm.D.

New Oral Anticoagulants in the Management of Atrial Fibrillation June, 2012 By Deborah K Brokaw, Pharm.D. New Oral Anticoagulants in the Management of Atrial Fibrillation June, 2012 By Deborah K Brokaw, Pharm.D. Introduction Since the 1950 s, the only orally available anticoagulant has been the vitamin K antagonist

More information

Anticoagulation and Reversal

Anticoagulation and Reversal Anticoagulation and Reversal John Howard, PharmD, BCPS Clinical Pharmacist Internal Medicine Affiliate Associate Clinical Professor South Carolina College of Pharmacy Disclosures I have no Financial, Industry,

More information

Antithrombotic alternatives for stroke prevention in atrial fibrillation: critical differences and remaining questions

Antithrombotic alternatives for stroke prevention in atrial fibrillation: critical differences and remaining questions The journal of interventions in clinical practice www.drugsincontext.com OPINION FULL TEXT ARTICLE Antithrombotic alternatives for stroke prevention in atrial fibrillation: critical differences and remaining

More information

How To Understand The History Of Analgesic Drugs

How To Understand The History Of Analgesic Drugs New Developments in Oral Anticoagulants: Treating and Preventing Embolic Events in the 21 st Century David Stewart, PharmD, BCPS Associate Professor of Pharmacy Practice East Tennessee State University

More information

The new oral anticoagulants & the future of haemostasis laboratory testing. Alcohol: the good, the bad and the ugly

The new oral anticoagulants & the future of haemostasis laboratory testing. Alcohol: the good, the bad and the ugly The new oral anticoagulants & the future of haemostasis laboratory testing Emmanuel J Favaloro Diagnostic Haemostasis Laboratory, Institute of Clinical Pathology & Medical Research, ICPMR, Pathology West,

More information

3/17/2014. No conflicts of interest to report

3/17/2014. No conflicts of interest to report No conflicts of interest to report Patrick M. Lewis, Pharm.D., BCPS, CACP Lahey Hospital & Medical Center Burlington, MA April 1 st 2014 Parts of this presentation discuss off-label use of reversal agents.

More information

Venous Thromboembolism: Long Term Anticoagulation. Dan Johnson, Pharm.D.

Venous Thromboembolism: Long Term Anticoagulation. Dan Johnson, Pharm.D. Venous Thromboembolism: Long Term Anticoagulation Dan Johnson, Pharm.D. Disclosures No financial relationships with products discussed Off-label use of drug therapy always discussed Objectives Review clinical

More information

New Oral Anticoagulants Increase Risk for Gastrointestinal Bleeding - A Systematic Review and Meta-Analysis

New Oral Anticoagulants Increase Risk for Gastrointestinal Bleeding - A Systematic Review and Meta-Analysis New Oral Anticoagulants Increase Risk for Gastrointestinal Bleeding - A Systematic Review and Meta-Analysis Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET Departments of Gastroenterology and Hepatology,

More information

Recommendations on Use of Dabigatran in Atrial Fibrillation

Recommendations on Use of Dabigatran in Atrial Fibrillation Recommendations on Use of Dabigatran in Atrial Fibrillation Developed by participants from the Section of Hematology/Oncology and Section of Cardiology, and Faculty of Pharmacy, University of Manitoba

More information

New Anticoagulation Options for Stroke Prevention in Atrial Fibrillation. Joy Wahawisan, Pharm.D., BCPS April 25, 2012

New Anticoagulation Options for Stroke Prevention in Atrial Fibrillation. Joy Wahawisan, Pharm.D., BCPS April 25, 2012 New Anticoagulation Options for Stroke Prevention in Atrial Fibrillation Joy Wahawisan, Pharm.D., BCPS April 25, 2012 Stroke in Atrial Fibrillation % Stroke 1991;22:983. Age Range (years) CHADS 2 Risk

More information

Disclosures. Objective (NRHS) Self Assessment #2

Disclosures. Objective (NRHS) Self Assessment #2 Development and Implementation of a Protocol for Reversing the Effects of Anticoagulants for Use in a Community Hospital Samantha Sepulveda, Pharm.D. PGY1 Pharmacy Resident Norman Regional Health System

More information

1/12/2016. What s in a name? What s in a name? NO.Anti-Coagulation. DOACs in clinical practice. Practical aspects of using

1/12/2016. What s in a name? What s in a name? NO.Anti-Coagulation. DOACs in clinical practice. Practical aspects of using What s in a name? Practical aspects of using DOACs (Direct Oral Anticoagulants) James L. Sebastian, MD, MACP Professor of Medicine (GIM) Medical College of Wisconsin February 5, 2016 DOAC NOAC NOAC ODI

More information

Reversing novel anticoagulants to divert catastrophe SEAN P. WILSON, MD DEPARTMENT OF EMERGENCY MEDICINE HENRY FORD HOSPITAL, DETROIT, MI

Reversing novel anticoagulants to divert catastrophe SEAN P. WILSON, MD DEPARTMENT OF EMERGENCY MEDICINE HENRY FORD HOSPITAL, DETROIT, MI Reversing novel anticoagulants to divert catastrophe SEAN P. WILSON, MD DEPARTMENT OF EMERGENCY MEDICINE HENRY FORD HOSPITAL, DETROIT, MI Novel anticoagulants? Dabigatran (Pradaxa) Stroke and systemic

More information

New Treatments for Stroke Prevention in Atrial Fibrillation. John C. Andrefsky, MD, FAHA NEOMED Internal Medicine Review course May 5 th, 2013

New Treatments for Stroke Prevention in Atrial Fibrillation. John C. Andrefsky, MD, FAHA NEOMED Internal Medicine Review course May 5 th, 2013 New Treatments for Stroke Prevention in Atrial Fibrillation John C. Andrefsky, MD, FAHA NEOMED Internal Medicine Review course May 5 th, 2013 Classification Paroxysmal atrial fibrillation (AF) Last < 7

More information

How To Compare The New Oral Anticoagulants

How To Compare The New Oral Anticoagulants Disclosures The New Oral Anticoagulants: Are they better than Warfarin? Alan P. Agins, Ph.D. does not have any actual or potential conflicts of interest in relation to this CE activity. Alan Agins, Ph.D.

More information

Post-ISTH review: Thrombosis-I New Oral Anticoagulants 臺 大 醫 院 內 科 部 血 液 科 周 聖 傑 醫 師

Post-ISTH review: Thrombosis-I New Oral Anticoagulants 臺 大 醫 院 內 科 部 血 液 科 周 聖 傑 醫 師 Post-ISTH review: Thrombosis-I New Oral Anticoagulants 臺 大 醫 院 內 科 部 血 液 科 周 聖 傑 醫 師 The antithrombotic efficacy is limited but the risk of bleeding is indefinite Fuster V et al. Circulation 2011;123:e269-e367

More information

The New Oral Anticoagulants: When and When Not to Use Them Philip C. Comp, M.D., Ph.D. Professor of Medicine, University of Oklahoma Health Sciences

The New Oral Anticoagulants: When and When Not to Use Them Philip C. Comp, M.D., Ph.D. Professor of Medicine, University of Oklahoma Health Sciences The New Oral Anticoagulants: When and When Not to Use Them Philip C. Comp, M.D., Ph.D. Professor of Medicine, University of Oklahoma Health Sciences Center September 25, 2015 Question: With which of the

More information

MCHENRY WESTERN LAKE COUNTY EMS SYSTEM OPTIONAL CE ADVANCED LEVEL (EMTP, PHRN, ECRN) August 2013. Anticoagulants

MCHENRY WESTERN LAKE COUNTY EMS SYSTEM OPTIONAL CE ADVANCED LEVEL (EMTP, PHRN, ECRN) August 2013. Anticoagulants MCHENRY WESTERN LAKE COUNTY EMS SYSTEM OPTIONAL CE ADVANCED LEVEL (EMTP, PHRN, ECRN) August 2013 Anticoagulants Anticoagulants are agents that prevent the formation of blood clots. Before we can talk about

More information

Objectives. New and Emerging Anticoagulants. Objectives (continued) 2/18/2014. Development of New Anticoagulants

Objectives. New and Emerging Anticoagulants. Objectives (continued) 2/18/2014. Development of New Anticoagulants Objectives New and Emerging Anticoagulants Adraine Lyles, PharmD, BCPS Clinical Pharmacy Specialist VCU Medical Center Describe the pharmacology of the novel oral anticoagulants Discuss the clinical evidence

More information

Oral Anticoagulants: What s New?

Oral Anticoagulants: What s New? Oral Anticoagulants: What s New? Sallie Young, Pharm.D., BCPS (AQ-Cardiology) Clinical Pharmacy Specialist, Cardiology Penn State Hershey Medical Center syoung1@hmc.psu.edu August 2012 Oral Anticoagulant

More information

DISCLOSURES CONFLICT CATEGORY. No conflict of interest to disclose

DISCLOSURES CONFLICT CATEGORY. No conflict of interest to disclose DISCLOSURES CATEGORY Employment Research support Scientific advisory board Consultancy Speakers bureau Major stockholder Patents Honoraria Travel support Other CONFLICT No conflict of interest to disclose

More information

Thrombosis and Hemostasis

Thrombosis and Hemostasis Thrombosis and Hemostasis Wendy Lim, MD, MSc, FRCPC Associate Professor, Department of Medicine McMaster University, Hamilton, ON Overview To review the important developments in venous thromboembolism

More information

Reversal of Antiplatelet and Anticoagulant Therapy: What You Need To Know. Ronald Walsh, MD Chief Medical Officer Community Blood Services

Reversal of Antiplatelet and Anticoagulant Therapy: What You Need To Know. Ronald Walsh, MD Chief Medical Officer Community Blood Services Reversal of Antiplatelet and Anticoagulant Therapy: What You Need To Know Ronald Walsh, MD Chief Medical Officer Community Blood Services HEMOSTATIC PROCESS Initiation and formation of the platelet plug

More information

Thrombosis management: A time for change practical management with NOACs Dr Wala Elizabeth Medical Director, Bayer Healthcare

Thrombosis management: A time for change practical management with NOACs Dr Wala Elizabeth Medical Director, Bayer Healthcare Thrombosis management: A time for change practical management with NOACs Dr Wala Elizabeth Medical Director, Bayer Healthcare Kenya Association of Physicians Conference 10 th May 2013 New anticoagulants:

More information

Rivaroxaban (Xarelto ) by

Rivaroxaban (Xarelto ) by Essentia Health Med Moment Short Video Tune-Up A brief overview of a new medication, or important new medication information Rivaroxaban (Xarelto ) by Richard Mullvain RPH BCPS (AQC) Current - August 2011

More information

Traditional anticoagulants

Traditional anticoagulants TEGH Family Practice Clinic Day April 4, 03 Use of Anticoagulants in 03: What s New (and What Isn t) Bill Geerts, MD, FRCPC Director, Thromboembolism Program, Sunnybrook HSC Professor of Medicine, University

More information

Anticoagulation in Atrial Fibrillation

Anticoagulation in Atrial Fibrillation Anticoagulation in Atrial Fibrillation Parag P. Patel, MD FACC Disclosures Eliquis Speakers Bureau 1 Clinical Scenario Ms. L is a 76F admitted to the stroke service with a dense right sided hemiparesis

More information

Troubled by warfarin s narrow therapeutic index, numerous

Troubled by warfarin s narrow therapeutic index, numerous Jeremy W. Vandiver, PharmD, BCPS; Douglas Faulkner, MD; Michael Erlandson, MD; Mary Onysko, PharmD, BCPS University of Wyoming School of Pharmacy, Laramie (Drs. Vandiver and Onysko); Hampden Medical Group,

More information

Breadth of indications matters One drug for multiple indications

Breadth of indications matters One drug for multiple indications Breadth of indications matters One drug for multiple indications Sylvia Haas, MD, PhD Formerly of the Technical University of Munich Munich, Germany Disclosures: Sylvia Haas 1 Novel oral anticoagulants:

More information

New Anticoagulants: What to Use What to Avoid

New Anticoagulants: What to Use What to Avoid New Anticoagulants: What to Use What to Avoid Bruce Davidson, MD, MPH Clinical Professor of Medicine Pulmonary and Critical Care Medicine Division University of Washington School of Medicine Seattle USA

More information

East Kent Prescribing Group

East Kent Prescribing Group East Kent Prescribing Group Rivaroxaban (Xarelto ) Safety Information Approved by the East Kent Prescribing Group. Approved by: East Kent Prescribing Group (Representing Ashford CCG, Canterbury and Coastal

More information

New Anticoagulants: When and Why Should I Use Them? Disclosures

New Anticoagulants: When and Why Should I Use Them? Disclosures Winship Cancer Institute of Emory University New Anticoagulants: When and Why Should I Use Them? Christine L. Kempton, MD, MSc Associate Professor of Pediatrics and Hematology and Medical Oncology Hemophilia

More information

Disclosure. New Agents for Treatment of DVT. Prevalence of DVT VTE. Normal Hemostasis 7/17/2015. Mark Oliver, MD, RVT, RPVI,FSVU

Disclosure. New Agents for Treatment of DVT. Prevalence of DVT VTE. Normal Hemostasis 7/17/2015. Mark Oliver, MD, RVT, RPVI,FSVU New Agents for Treatment of DVT Disclosure PI Adopt and Amplify trials Mark Oliver, MD, RVT, RPVI,FSVU BMS and Pfizer Speaker VTE Venous Thromboembolism Recognized DVT s New : 170,000 Recurrent : 90,000

More information

3/3/2015. Patrick Cobb, MD, FACP March 2015

3/3/2015. Patrick Cobb, MD, FACP March 2015 Patrick Cobb, MD, FACP March 2015 I, Patrick Cobb, MD, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict

More information

xaban) Policy covered: Coverage of following criteria: the following those who meet the or Hip Xarelto is For those impacted by this policy.

xaban) Policy covered: Coverage of following criteria: the following those who meet the or Hip Xarelto is For those impacted by this policy. Xarelto (rivarox xaban) Policy Number: 5.01.575 Origination: 06/2014 Last Review: 07/2015 Next Review: 07/2016 Policy BCBSKC will provide coverage for Xarelto when it is determined to be medically necessary

More information

Blood products and pharmaceutical emergencies

Blood products and pharmaceutical emergencies Blood products and pharmaceutical emergencies Kasey L. Bucher PharmD, BCPS Clinical Specialist, Emergency Medicine Mercy Health Saint Mary s September 12, 2013 Disclosures None significancemagazine.com

More information

New Oral Anticoagulants. How safe are they outside the trials?

New Oral Anticoagulants. How safe are they outside the trials? New Oral Anticoagulants How safe are they outside the trials? Objectives The need for anticoagulant therapy Indications for anticoagulation Traditional anticoagulant therapies Properties of new oral anticoagulants

More information

New Anticoagulation Agents and Their Reversal Agents. Objectives. Background 12/21/2015

New Anticoagulation Agents and Their Reversal Agents. Objectives. Background 12/21/2015 New Anticoagulation Agents and Their Reversal Agents Jay Hazelcorn, Pharm.D. PGY-1 Pharmacy Resident Broward Health Medical Center Objectives Review the pharmacology, indications, and place in therapy

More information

MEDICAL ASSISTANCE HANDBOOK PRIOR AUTHORIZATION OF PHARMACEUTICAL SERVICES. A. Prescriptions That Require Prior Authorization

MEDICAL ASSISTANCE HANDBOOK PRIOR AUTHORIZATION OF PHARMACEUTICAL SERVICES. A. Prescriptions That Require Prior Authorization MEDICAL ASSISTANCE HBOOK PRI AUTHIZATION OF PHARMACEUTICAL SERVICES I. Requirements for Prior Authorization of Anticoagulants A. Prescriptions That Require Prior Authorization Prescriptions for Anticoagulants

More information

Management for Deep Vein Thrombosis and New Agents

Management for Deep Vein Thrombosis and New Agents Management for Deep Vein Thrombosis and New Agents Mark Malesker, Pharm.D., FCCP, FCCP, FASHP, BCPS Professor of Pharmacy Practice and Medicine Creighton University 5 th Annual Creighton Cardiovascular

More information

How To Manage An Anticoagulant

How To Manage An Anticoagulant PERI-OPERATIVE MANAGEMENT OF PATIENTS WHO ARE RECEIVING A NEW ORAL ANTICOAGULANT (DABIGATRAN, RIVAROXABAN, APIXABAN) TARGET AUDIENCE: All Canadian health care professionals, including primary care physicians,

More information

The New Anticoagulants are Here! Do you know how to use them? Arrhythmia Winter School February 11 th, 2012. Jeff Healey

The New Anticoagulants are Here! Do you know how to use them? Arrhythmia Winter School February 11 th, 2012. Jeff Healey The New Anticoagulants are Here! Do you know how to use them? Arrhythmia Winter School February 11 th, 2012 Jeff Healey RELY: A New Era in AF Connolly SJ et al. N Engl J Med 2009;361:1139-1151 ROCKET-AF:

More information

Bios 6648: Design & conduct of clinical research

Bios 6648: Design & conduct of clinical research Bios 6648: Design & conduct of clinical research Section 1 - Specifying the study setting and objectives 1. Specifying the study setting and objectives 1.0 Background Where will we end up?: (a) The treatment

More information

New Anticoagulants for the Treatment of Thromboembolism With a little subplot on superficial thrombophlebitis. Mark Crowther

New Anticoagulants for the Treatment of Thromboembolism With a little subplot on superficial thrombophlebitis. Mark Crowther New Anticoagulants for the Treatment of Thromboembolism With a little subplot on superficial thrombophlebitis Mark Crowther 1 Disclosures Advisory Boards in last 24 months Pfizer, Alexion, Bayer, CSL Behring,

More information

Novel Anticoagulants

Novel Anticoagulants Novel Anticoagulants Mark T. Reding, MD Associate Professor of Medicine Division of Hematology, Oncology, and Transplantation Director, Center for Bleeding and Clotting Disorders University of Minnesota

More information

DOACs. What s in a name? or TSOACs. Blood Clot. Darra Cover, Pharm D. Clot Formation DOACs work here. Direct Oral AntiCoagulant

DOACs. What s in a name? or TSOACs. Blood Clot. Darra Cover, Pharm D. Clot Formation DOACs work here. Direct Oral AntiCoagulant DOACs NOACs or TSOACs Generic Name DOACs Brand Name Mechanism of Action Direct Xa Inhibitor Direct Thrombin Inhibitor Dabigatran Pradaxa X Rivaroxaban Xarelto X Darra Cover, Pharm D Apixaban Eliquis X

More information

Eliquis. Policy. covered: Eliquis is. indicated to. reduce the. therapy. Eliquis is. superior to. of 32 to. Eliquis is AMPLIFY. nonfatal. physicians.

Eliquis. Policy. covered: Eliquis is. indicated to. reduce the. therapy. Eliquis is. superior to. of 32 to. Eliquis is AMPLIFY. nonfatal. physicians. Eliquis (apixaban) Policy Number: 5.01.573 Origination: 06/2014 Last Review: 07/2015 Next Review: 07/2016 Policy BCBSKC will provide coverage for Eliquis when it is determined to be medically necessary

More information

Kevin Saunders MD CCFP Rivergrove Medical Clinic Wellness Institute @ SOGH April 17 2013

Kevin Saunders MD CCFP Rivergrove Medical Clinic Wellness Institute @ SOGH April 17 2013 Kevin Saunders MD CCFP Rivergrove Medical Clinic Wellness Institute @ SOGH April 17 2013 Family physician with Rivergrove Medical Clinic Practice in the north end since 1985 Medical Director of the Wellness

More information

The speakers have attested that their presentation will be free of all commercial bias toward a specific company and its products.

The speakers have attested that their presentation will be free of all commercial bias toward a specific company and its products. Update on New Anticoagulants (Apixaban, Dabigatran and Rivaroxaban) Patient Safety Daniel B. DiCola, MD and Paul Ament,, Pharm.D Excela Heath, Latrobe, PA Disclosures: Paul Ament discloses that he receives

More information