Like LMWH, fondaparinux is given subcutaneously and has predictable absorption and degree of anticoagulation. Heparin-induced thrombocytopenia should be suspected if a patient's platelet count decreases by at least 50 percent, or is less than 150 103 per L after initiation of heparin. Heparin or LMWH should be administered at initiation of the vitamin K antagonist and be continued for a minimum of five days and until the international normalized ratio (INR) is in the targeted therapeutic range for a minimum of 24 hours. The study found that effectiveness was similar for all oral anticoagulants and risk of major hemorrhage was reduced among dabigatran users when compared with rivaroxaban (but not vitamin K antagonists) in patients with a moderate-to-high burden of chronic conditions.26 Rates of gastrointestinal hemorrhage were highest in the rivaroxaban group. If the INR is not within the desired therapeutic range after excluding explanatory factors, a 5 to 20 percent increase or decrease in the total weekly dosage is required.46 Patients should be provided with the simplest regimen to achieve the new total weekly dosage. The recently published American Heart Association (AHA) /American College of Cardiology (ACC)/Heart Rhythm Society (HRS) guidelines recommend a direct oral anticoagulant over vitamin K antagonists, unless the patient has moderate-to-severe mitral stenosis or a mechanical heart valve. Patients taking warfarin in the evening can adjust their dosing based on that day's INR results. Compared with vitamin K antagonists, direct oral anticoagulants are associated with a reduction in the incidence of stroke of 21% to 35% and a reduction in the incidence of intracranial hemorrhage of 33% to 60%.2225, One comparative effectiveness analysis looked at the treatment of patients with atrial fibrillation who may not have been well-represented in clinical trials because of multiple comorbidities.26 This study used Medicare data to compare vitamin K antagonists with dabigatran and rivaroxaban in patients with atrial fibrillation and multiple chronic conditions. Kcentra is preferred over a fresh frozen plasma infusion because of its smaller volume, faster infusion rate, and superior effectiveness in INR reduction. Validated bleeding risk assessments such as HAS-BLED should be performed at each visit and modifiable factors should be addressed. Copyright 2019 by the American Academy of Family Physicians. Author disclosure: No relevant financial affiliations. Last Updated: April 2019 Vitamin K Antagonists: Warfarin (Coumadin) o Warfarin may be held, or reduced, with INR correction in 2-5 days for MOST patients. Do not administer plasma or prothrombin complex concentrates for nonemergent reversal of vitamin K antagonists (i.e., outside of the setting of major bleeding, intracranial hemorrhage, or anticipated emergent surgery). Although LMWH has a similar bleeding risk and lower heparin-induced thrombocytopenia risk compared with unfractionated heparin, a patient with a history of heparin-induced thrombocytopenia should not take LMWH.1, Fondaparinux (Arixtra) is a synthetic analogue of heparin. In addition, rivaroxaban (Xarelto) and dabigatran have a higher risk of gastrointestinal bleeding compared with apixaban.15 Real world experience with direct oral anticoagulants in terms of safety and effectiveness seems consistent with published trials.15,16, In patients who have had acute ischemic stroke, the prevalence of comorbid atrial fibrillation is increasing, and atrial fibrillationassociated strokes have a higher mortality rate.17 One study found that treatment decisions are often not guideline adherent.18 The CHADS2 (congestive heart failure; hypertension; age 75 years or older; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism [doubled]) tool (https://www.mdcalc.com/chads2-score-atrial-fibrillation-stroke-risk) or CHA2DS2-VASc (congestive heart failure; hypertension; age 75 years or older [doubled]; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism [doubled]; vascular disease; age 65 to 74 years; sex category) tool (https://www.mdcalc.com/cha2ds2-vasc-score-atrial-fibrillation-stroke-risk) can be used to estimate the risk of stroke. Although there is a small subset of patients who may have unexpected responses to warfarin, it is not currently recommended that patients undergo genetic testing.1. Data Sources: A PubMed search was completed in Clinical Queries using the key terms outpatient, anticoagulation, warfarin, dabigatran, rivaroxaban, heparin, low-molecular-weight heparin, dalteparin, enoxaparin, patient self-monitor, and INR. Patients taking warfarin (Coumadin) should be treated using systematic processes of care to optimize effectiveness and minimize adverse effects. PATRICIA WIGLE, PharmD, BRAD HEIN, PharmD, AND CHRISTOPHER R. BERNHEISEL, MD. This guideline outlines the evidence for managing anticoagulation therapy with oral vitamin K antagonist (warfarin) for adult patients in the ambulatory setting. Two LMWHs, dalteparin (Fragmin) and enoxaparin (Lovenox), are commonly used in clinical practice. In patients with atrial fibrillation and at least one other risk factor for stroke, newer agents (rivaroxaban [Xarelto] and dabigatran [Pradaxa]) that do not require frequent laboratory monitoring are as effective as warfarin for prevention of stroke or systemic embolism and have comparable risks of major bleeding. Optimal dose, duration, and the need for repeat dosing and mitigation of thromboembolic risk have yet to be delineated. The ANNEXA-4 study showed that 79% of patients with acute major bleeding treated with andexanet alfa achieved effective hemostasis.30 Key selected exclusion criteria from this study included impending surgery, a major thrombotic event within two weeks before enrollment, intracranial hemorrhage with a Glasgow Coma Scale score of less than 7, or receipt of one of the following agents within seven days before screening: vitamin K antagonist, dabigatran, 4-factor prothrombin complex concentrate, blood, or plasma. Reviewed and approved by: UNMH Anticoagulation Subcommittee, UNMH P&T Committee Approval date: March 2013 Last updated: June 2020 4 V. Warfarin dosing nomogram for MAINTENANCE therapy ( 1 week of warfarin therapy) of non-bleeding patients5 Primarily geared toward outpatient therapy. LMWH and select direct oral anticoagulants can be used for anticoagulation therapy initiation on an outpatient basis. Warfarin, a vitamin K antagonist, is recommended for the treatment of venous thromboembolism and for the prevention of stroke in persons with atrial fibrillation, atrial flutter, or valvular heart disease. See permissionsforcopyrightquestions and/or permission requests. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. In the ARISTOTLE and AVERROES trials, apixaban reduced the primary outcome of ischemic stroke, hemorrhagic stroke, and systemic embolism compared with warfarin and aspirin, respectively. LMWH is derived from unfractionated heparin and has an increased affinity for factor Xa relative to thrombin.1 LMWH, which is given subcutaneously, has predictable absorption and degree of anticoagulation. After a baseline INR is determined, the next INR should be obtained after the patient has received two or three doses of the vitamin K antagonist. ED is often a symptom of another health problem or health-related factor. Vitamin K antagonists are subject to many drug interactions. Dabigatran's safety profile needs further evaluation.13. The immediate effect of direct oral anticoagulants permits select patients at low risk to initiate treatment in the outpatient setting for venous thromboembolism, including pulmonary embolism. Characteristics of these anticoagulants are provided in Table 5913 and eTable B. Most of the recommendations are based on the 10th edition of the American College of Chest Physicians (ACCP) guidelines on antithrombotic therapy for VTE disease (Table 1).15, Indications for initiation and duration of therapy for vitamin K antagonists, direct oral anticoagulants, and LMWH are listed in Table 2.1. Physicians should not automatically consider all patients taking vitamin K antagonists to be good candidates for direct oral anticoagulants because of the diversity in the characteristics of these medications. Rivaroxaban is indicated for the prevention of deep venous thrombosis in patients undergoing knee or hip replacement surgery, for treatment of deep venous thrombosis and pulmonary embolism, for reducing the risk of recurrent deep venous thrombosis and pulmonary embolism after initial treatment, and for prevention of systemic embolism in patients with nonvalvular atrial fibrillation. The 2019 National Comprehensive Cancer Network guidelines on cancer-associated VTE include rivaroxaban as a monotherapy option.34 Apixaban is included as an acceptable alternative for patients who refuse LMWH or who have compelling reasons to avoid LMWH.35. This activity reviews the indications, action, and contraindications for warfarin as a valuable agent in the prophylaxis and treatment of myocardial infarction, deep vein thrombosis, pulmonary . One of the roles of a professional body is . Low-risk procedures in patients treated with direct oral anticoagulants (DOACs): Omit the DOAC the morning of the procedure. This can be problematic when determining the appropriate management in a patient who needs emergent surgery. Download for Apple devices. The ACC published an expert consensus decision pathway in 2017 on the management of bleeding for patients taking oral anticoagulants.28 Management of bleeding for patients taking vitamin K antagonists depends on the severity of the bleed. PATRICIA WIGLE, PharmD, BCPS, BRADLEY HEIN, PharmD, HANNA E. BLOOMFIELD, MD, MPH, MATTHEW TUBB, MD, PhD, AND MICHAEL DOHERTY, PharmD, BCACP. Unfractionated heparin is a mixture of glycosaminoglycans that works by binding to antithrombin to inactivate thrombin (factor IIa) and factor Xa.1 It also prevents the growth and potential propagation of clots. Subcutaneous LMWH has a predictable absorption and degree of anticoagulation, so monitoring with antifactor Xa levels is not routinely recommended. Optimal dose, duration, need for repeat dosing, and mitigation of thromboembolic risk is yet to be delineated. The American College of Chest Physicians provides recommendations for the use of anticoagulant medications for several indications that are important in the primary care setting. During this initial period, the patient can enter a hypercoagulable state caused by warfarin's effects on proteins C and S.1 Heparin or LMWH should be administered with warfarin initiation and continued until the INR has been in the targeted therapeutic range for a minimum of 24 hours. Foods with high vitamin K concentrations, such as leafy green vegetables, have the potential to partially reverse anticoagulation effects of the vitamin K antagonist.4 A consistent diet is more important than limiting dietary vitamin K. Considerations for parenteral medications are provided in eTable A. Dalteparin (Fragmin) and enoxaparin (Lovenox) are commonly used LMWHs in clinical practice. Direct oral anticoagulants have fewer overall drug-drug interactions (Table 65,913); a comparable (if not lower) bleeding rate; a shorter half-life; and fixed dosing based on indication, drug interactions, and renal or hepatic function. The following are key points to remember from this review on anticoagulation in concomitant chronic kidney disease (CKD) and atrial fibrillation (AF): AF and CKD often coexist as they share multiple risk factors, including hypertension, diabetes mellitus, and coronary artery disease. Patients on warfarin therapy should be treated using a systematic process to optimize effectiveness and minimize adverse effects. Andexanet alfa has been approved to reverse the anticoagulant effects of rivaroxaban and apixaban in patients with life-threatening or uncontrolled bleeding. Then, the frequency of INR monitoring decreases to twice weekly until the INR is within the therapeutic range, then weekly, every other week, and finally monthly.1 The ACCP guidelines allow clinicians to consider INR monitoring up to every 12 weeks in patients who are stable (defined as having at least three months of consistent results with no need to adjust warfarin dosing). Characteristics of these anticoagulants are provided in Tables 4 and 5.1019, FDA boxed warning: increased risk of stroke in patients with nonvalvular atrial fibrillation who discontinue apixaban without adequate continuous anticoagulation, Contraindications: active pathological bleeding; history of serious hypersensitivity reaction to apixaban, Use not recommended in patients with prosthetic heart valves or severe hepatic impairment; pregnant or breastfeeding patients, Contraindications: active pathological bleeding; history of serious hypersensitivity reaction to dabigatran; mechanical prosthetic heart valve, Use not recommended in patients with bioprosthetic heart valves; pregnant or breastfeeding patients, FDA boxed warning: increased risk of thrombotic events in patients with nonvalvular atrial fibrillation who discontinue rivaroxaban without adequate continuous anticoagulation; risk of epidural/spinal hematoma in patients receiving neuraxial anesthesia or in patients undergoing spinal puncture while taking rivaroxaban, Contraindications: active pathological bleeding; history of severe hypersensitivity reaction to rivaroxaban, Reduce risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, Prevent DVT in patients undergoing knee or hip replacement surgery, Reduce risk of recurrent DVT and pulmonary embolism after initial treatment, 2.5 mg twice daily if patient has at least 2 of the following: age 80 years or older, body weight of 132 lb (60 kg) or less, or serum creatinine level of 1.5 mg per dL or higher, No data for patients on dialysis or with CrCl < 15 mL/min/1.73 m2 or patients with moderate hepatic impairment, Not recommended for patients with severe hepatic impairment, 2.5 mg twice daily if patient is on a strong dual inhibitor of CYP3A4 and P-glycoprotein (e.g., ketoconazole, itraconazole [Sporanox], ritonavir [Norvir], clarithromycin [Biaxin]); avoid use of these drugs if patient is already taking 2.5 mg twice daily, CrCl 30 to 50 mL/min/1.73 m2 and concurrent use of dronedarone (Multaq) or systemic ketoconazole: decrease dosage to 75 mg twice daily, CrCl 15 to 30 mL/min/1.73 m2: decrease dosage to75 mg twice daily, CrCl < 30 mL/min/1.73 m2 and concurrent use of a P-glycoprotein inhibitor: avoid use, DVT prophylaxis and CrCl < 30 mL/min/1.73 m2: avoid use, Prevent stroke in patients with nonvalvular atrial fibrillation: 20 mg once daily, Prevent stroke in patients with nonvalvular atrial fibrillation and CrCl 15 to 50 mL/min/1.73 m2: 15 mg once daily, Prevent stroke in patients with nonvalvular atrial fibrillation and CrCl < 15 mL/min/1.73 m2: avoid use, Treat DVT and pulmonary embolism or reduce risk of future DVT and pulmonary embolism after initial treatment: 15 mg twice daily with food for 21 days, then20 mg once daily for the remainder of the treatment interval (six months total) or for long-term risk reduction; avoid in patients with CrCl < 30 mL/min/1.73 m2, See usual dosage for dose modification information, Avoid use of strong dual inhibitor of CYP3A4 and P-glycoprotein in patients taking apixaban, 2.5 mg twice daily, Avoid use of strong dual inducer of CYP3A4 and P-glycoprotein (e.g., carbamazepine [Tegretol], phenytoin [Dilantin], rifampin, St. John's wort), Increased bleeding risk with certain medications (e.g., clopidogrel [Plavix], nonsteroidal anti-inflammatory drugs), Avoid concurrent use with P-glycoprotein inducers (e.g., rifampin), Evaluate P-glycoprotein inhibitors individually*, Increased bleeding risk with certain medications (e.g., clopidogrel, nonsteroidal anti-inflammatory drugs), Avoid with combined P-glycoprotein inhibitor and CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, ritonavir, conivaptan [Vaprisol]), Avoid with combined P-glycoprotein inducer and CYP3A4 inducer (e.g., carbamazepine, phenytoin, rifampin, St. John's wort), Note differences in recommendation for dosage adjustments in renal impairment based on indication, Dosing recommendations for patients with moderate hepatic impairment are not available, No specific recommendations are made regarding hepatic impairment, Avoid if moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment or with any hepatic disease associated with coagulopathy, Refer to package labeling for information on conversion from or to warfarin (Coumadin) or parenteral anticoagulants, and on intervention for surgery, Do not chew, break, open capsules; capsules must be dispensed in original container and not repackaged because of sensitivity to moisture, Need more information about use in patients under and over ideal body weight, Refer to package labeling for information on conversion from or to warfarin or parenteral anticoagulants, and on intervention for surgery, Rivaroxaban should be stopped 24 hours before major surgery, The first dose should be initiated 6 to 10 hours after surgery, Recommended duration of therapy is 12 days for total knee replacement and 35 days for total hip replacement, Prevent stroke in patients with atrial fibrillation, When transitioning from warfarin to rivaroxaban, give first dose of rivaroxaban when the international normalized ratio is less than 3, Lower bleeding risk compared with warfarin, At least as effective and possibly superior at reducing total venous thromboembolism without increasing major bleeding risk, Lack of long-term safety/effectiveness data, U.S. Food and Drug Administration boxed warning for increased risk of thrombotic events when apixaban discontinued in patients with nonvalvular atrial fibrillation, Underweight patients and those with renal impairment may be at increased bleeding risk, Lack of long-term safety/effectiveness data (e.g., dyspepsia, hepatotoxicity, myocardial infarction), Packaging does not allow redistribution to pill boxes, Noncompliance with medication potentially more harmful, U.S. Food and Drug Administration boxed warning for increased risk of thrombotic events when rivaroxaban discontinued in patients with nonvalvular atrial fibrillation, Lack of long-term safety/effectiveness data (e.g., hepatotoxicity), Cannot use in patients with moderate or severe hepatic impairment, By alleviating the need for frequent dose titrations and laboratory monitoring, especially with therapy initiation and new drug additions or deletions, apixaban possesses key clinical advantages compared with warfarin, Warfarin's predictable adverse effect profile, once-daily administration, reversibility with vitamin K, and ability to be monitored for sub-and supratherapeutic dosing provide reassurance for the clinician, By alleviating the need for frequent dose titrations and laboratory monitoring, especially with therapy initiation and new drug additions or deletions, dabigatran possesses key clinical advantages compared with warfarin, Warfarin's predictable adverse effect profile, once-daily administration, reversibility with vitamin K, and ability to be monitored for sub- and supratherapeutic dosing provide reassurance for the clinician, By alleviating the need for frequent dose titrations and laboratory monitoring, especially with therapy initiation and new drug additions or deletions, rivaroxaban possesses key clinical advantages compared with warfarin, Warfarin's predictable adverse effect profile, once-daily administration, relatively longer half-life, reversibility with vitamin K, and ability to be monitored for sub- and supratherapeutic dosing provide reassurance for the clinician, Oral administration makes it easier to allow for longer duration of deep venous thrombosis prophylaxis in patients undergoing orthopedic surgery. In this prospective cohort study, we aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) versus heparin/vitamin K antagonists for the treatment of venous thromboembolism (VTE) in patients with inherited thrombophilia. Eur Heart J. Major bleeding should be treated with vitamin K and 4-factor prothrombin complex concentrate for patients already being treated with a vitamin K antagonist. The targeted INR range depends on indication for use and, at times, patient comorbidities. Dabigatran and apixaban are indicated for the prevention of systemic embolism and stroke in persons with nonvalvular atrial fibrillation. For all warfarin indications, perioperative bridging is not indicated in patients at low risk of thromboembolism.1 For patients with a high risk of thromboembolism, bridging with a therapeutic dose of unfractionated heparin or LMWH is indicated.1 The ACCP guidelines are less clear about how patients with a moderate risk of thromboembolism should be treated.1 Clinicians need to balance the individual's risk of thromboembolism, based on the medical history and surgical procedure, and risk of bleeding when determining what is optimal in persons in this moderate-risk category. The international normalized ratio goal and duration of treatment with warfarin vary depending on indication and risk. Cost can limit availability and use of andexanet alfa. Cause of elevated INR should be investigated. Since dabigatran's approval, four additional direct oral factor Xa inhibitors have been approved. Search date: August 10, 2012. The ACCP guidelines recommend fondaparinux for general surgical prophylaxis in patients who have contraindications to LMWH.1. Rationale Anticoagulation medications are high-risk medications due to complex dosing, insufficient monitoring, and inconsistent patient compliance. Bridging with low-molecular-weight heparin or other agents is based on balancing the risk of thromboembolism with the risk of bleeding. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. Decreased mortality, enhanced INR control, decreased thromboembolic events, and an improvement in patient satisfaction and quality of life have been demonstrated with patient self-testing, all without an increase in bleeding complications.2224 In 2008, the Centers for Medicare and Medicaid Services expanded its patient self-testing coverage,25 which is outlined in eTable D. 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