Recent evidence suggests that bridging anticoagulation should be avoided in patients undergoing procedures with high bleeding risk who are not at high thromboembolic risk. Selection and pre-operative discontinuation of bridging medication. The type of procedure being performed dictates when bridging anticoagulation should resume. In patients who have undergone surgeries that involve high bleeding risk, LMWH should not be administered until hours post-surgery Grade 2C evidence. Of note, enoxaparin administered in one single daily dose, as compared to divided doses, is associated with a greater risk of post-operative bleeding.
UFH bridging should resume post-operatively without a bolus dose at 24 hours in low-risk bleeding cases or hours in high-risk bleeding cases Grade 2C evidence. On occasion, unanticipated adjustments to surgical cases—or complications—change the previously determined post-operative bleeding risk.
When to restart long-term vitamin K antagonists VKA post-procedure. In most instances, regardless of pre-operative bleeding risk stratification, the resumption of VKA may occur once post-operative hemostasis has been achieved and the patient has been instructed to resume eating by the proceduralist or surgeon.
This most often occurs on the calendar day following surgery, because it takes approximately five days for an INR to achieve therapeutic levels. Given the high risk of thrombosis, the decision was made to bridge with LMWH.
Although the patient underwent the operation without significant bleeding, the adjustment from an exploratory laparoscopy to an open laparotomy increased her post-operative bleeding risk from medium to high.
Therefore, bridging anticoagulation with LMWH was resumed no sooner than 48 hours after the operation. Her warfarin was restarted on the day following surgery, once she resumed her diet. Hospitalists must understand both the pre- and post-procedure thrombotic risks, as well as the pre- and post-procedural bleeding risks, when determining the selection and logistics of initiation and cessation of antithrombotic bridging for inpatients.
Kerbel is a hospitalist at the University of California Los Angeles. Skip to main content. Patient Care. The Hospitalist. Key Points The CHADS2 score, the presence of heart valve type and location, and the duration of time since previous VTE events help guide our understanding of the peri-procedural thrombotic risk in patients with atrial fibrillation, mechanical heart valves, and prior VTE. The type of procedure and the presence of inherited or acquired bleeding diatheses guides our understanding of the bleeding risk.
Patients at high risk for thrombotic events should receive bridging anticoagulation, while patients at low risk do not require bridging anticoagulation.
N Engl J Med. January CT, et al. Lip GY, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Douketis JD, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. Connolly SJ, et al. J Am Coll Cardiol. Friberg L, et al.
In most patients, warfarin should be initiated as a maintenance dosage of 5 mg daily. Older patients and persons with liver disease, poor nutritional status, or heart failure may require lower initiation dosages. 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.
If a patient's INR becomes subtherapeutic or supratherapeutic, the frequency of monitoring should be increased until it stabilizes again. Option 1: Decrease or hold dosage, increase frequency of monitoring, and resume at lower dosage once INR is within the therapeutic range. Option 2: May continue current dosage if INR is minimally elevated 0. Hold next one or two doses, increase frequency of monitoring, and resume at lower dosage once INR is within the therapeutic range.
Hold warfarin Coumadin and administer vitamin K grade 2C , increase frequency of monitoring, repeat vitamin K as necessary, and resume warfarin at an appropriate dosage when INR is within the therapeutic range. Patients taking warfarin in the evening can adjust their dosing based on that day's INR results. 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.
Drug, Food, and Disease State Interactions. Warfarin is subject to many drug-drug, drug-food, and drug—disease state interactions.
Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.
Consult Pharm. Dronedarone and vitamin K antagonists: a review of drug-drug interactions. Am Heart J. Krajewski KC. Inability to achieve a therapeutic INR value while on concurrent warfarin and rifampin. J Clin Pharmacol. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J Thromb Thrombolysis. Some medications, such as amiodarone and rifampin, can impact a patient's INR long after the medication is discontinued.
Foods with high vitamin K concentrations, such as leafy green vegetables, have the potential to partially reverse the anticoagulation effects of warfarin. Medical conditions such as diarrhea, heart failure, fever, hyperthyroidism, and liver disease can potentiate warfarin's effects.
Conversely, conditions such as hypothyroidism can decrease the expected effects of warfa-rin. 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.
Unfractionated heparin is a mixture of glycosaminoglycans that works by binding to antithrombin to inactivate thrombin factor IIa and factor Xa. Considerations for parenteral medications are provided in eTable B. Activated partial thromboplastintime or anti—factor Xa levels. Unfractionated heparin can bemonitored using the activatedpartial thromboplastin time withan institution-specific goal range orwith anti—factor Xa levels, typicallyusing a goal of 0.
Unfractionated heparin vs. LMWH Considered equally effective and safe. Unfractionated heparin may be better for patients with highbleeding risk because of short half-life and reversibility. Enoxaparin Lovenox 1 mg per kg SC every12 hours or 1. A peak level 4 hours after the doseis given can be measured, witha goal of 0. Anti—factor Xa levels only iffondaparinux is the referencestandard for the assay. Longer half-life for fondaparinux is advantageous daily dosing and potentially troublesome adverse effects and lack ofreversibility.
Food and Drug Administration for treatment of acute deepvenous thrombosis. Enoxaparin, 1. Lovenox enoxaparin sodium injection for subcutaneous and intravenous use [prescribing information]. Bridgewater, N. Accessed May 25, Innohep tinzaparin sodium injection [prescribing information]. Ballerup, Denmark: Leo Pharmaceutical Products; Arixtra fondaparinux sodium solution for subcutaneous injection [prescribing information].
Research Triangle Park, N. Accessed August 1, Beyond increased bleeding risk, unfractionated heparin is associated with other adverse effects, such as heparin-induced thrombocytopenia. This generally occurs five to 14 days after initiation, and can occur after heparin is discontinued. LMWH is derived from unfractionated heparin and has an increased affinity for factor Xa relative to thrombin. Monitoring with measurement of anti—factor Xa levels is not routinely recommended, but is potentially useful in certain situations in which predictability of the degree of anticoagulation may be altered, such as changes in pharmacokinetics and pharmacodynamics e.
In the outpatient setting, the usefulness of laboratory testing is limited to the assessment of bleeding events and therapeutic failures. It may also be of value to assess levels infrequently during the course of long-term therapy i. 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. Fondaparinux Arixtra is a synthetic analogue of heparin.
Like LMWH, fondaparinux is given subcutaneously and has predictable absorption and degree of anticoagulation. There are few data on the monitoring of fondaparinux. Anti—factor Xa levels can be used as long as fondaparinux and not LMWH is the reference standard in the assay. In the treatment of VTE and pulmonary embolism, the parenteral anticoagulant should be overlapped with warfarin for a minimum of five days.
In most cases, warfarin can be initiated on day 1, after the first dose of the parenteral agent has been given. Warfarin should not be initiated alone, and the parenteral anticoagulant should not be discontinued until the INR is in the therapeutic range for two consecutive days. Depending on the patient's risk of thromboembolism and bleeding, bridging should occur when a patient's oral anticoagulation therapy needs to be interrupted eTable C. Interruption is common in patients undergoing surgery.
For most persons who are not having a minor procedure, warfarin will be stopped approximately five days before surgery and restarted 12 to 24 hours postoperatively. LMWH should be restarted approximately 24 hours after the procedure, and it may be prudent to wait 48 to 72 hours before resuming the medication for patients at high risk of bleeding or who are undergoing major surgery.
At least 1 of the following: Aortic valve prosthesis caged-ball ortilting-disk. Dental: continue warfarin with an oral prohemostatic agent or stop warfarin2 to 3 days before procedure. Aortic valve prosthesis bileaflet and atleast 1 of the following: age older than75 years; atrial fibrillation; congestiveheart failure; diabetes mellitus;hypertension; prior stroke or TIA.
Aortic valve prosthesis bileaflet withoutatrial fibrillation and no other stroke riskfactors. Bleeding risk in hospitalized patients has been linked to multiple factors including active gastric or duodenal ulcer,bleeding within 3 months before admission, and thrombocytopenia. Outpatient management of anticoagulation therapy. Am Fam Physician. Douketis JD. Perioperative management of patients who are receiving warfarin therapy: an evidence-based and practical approach.
Kaatz S, Paje D. Update in bridging anticoagulation. For all warfarin indications, perioperative bridging is not indicated in patients at low risk of thromboembolism. The effectiveness of warfarin is well-established; however, it is a suboptimal anticoagulant because it requires frequent monitoring and dosage adjustments, and because of its potential for multiple drug-drug, drug-food, and drug—disease state interactions.
It has a lengthy half-life and a delayed anticoagulant effect, and it often requires bridging therapy. Since the approval of warfarin in , no other oral option existed for patients who needed long-term anticoagulation therapy. This changed in with the U. Characteristics of these anticoagulants are provided in Tables 4 and 5.
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.
Contraindications: active pathological bleeding; history of severe hypersensitivity reaction to rivaroxaban. Reduce risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. John's wort. Increased bleeding risk with certain medications e. Note differences in recommendation for dosage adjustments in renal impairment based on indication. 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.
Refer to package labeling for information on conversion from or to warfarin or parenteral anticoagulants, and on intervention for surgery. Recommended duration of therapy is 12 days for total knee replacement and 35 days for total hip replacement.
When transitioning from warfarin to rivaroxaban, give first dose of rivaroxaban when the international normalized ratio is less than 3. Food and Drug Administration. Other P-glycoprotein inhibitors should be evaluated on an individual basis. Information from references 10 through At least as effective and possibly superior at reducing total venous thromboembolism without increasing major bleeding risk. Food and Drug Administration boxed warning for increased risk of thrombotic events when apixaban discontinued in patients with nonvalvular atrial fibrillation.
Food and Drug Administration boxed warning for increased risk of thrombotic events when rivaroxaban discontinued in patients with nonvalvular atrial fibrillation. 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. Dabigatran is available as a fixed-dose medication for the prevention of systemic embolism and stroke in patients with nonvalvular atrial fibrillation.
Without applicable laboratory monitoring, there is no mechanism to establish if a patient's INR is subtherapeutic or supratherapeutic. If the patient's INR is supratherapeutic, there is no antidote for reversal. This can be problematic when determining the appropriate management in a patient who needs emergent surgery. The short half-life is potentially challenging when assessing the impact of noncompliance or missing the second daily dose.
Limited data are available for patients with hepatic impairment and for patients who are obese.
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