Which Patients Should Receive Bridging Anticoagulation? – The Hospitalist



Case

A 77-year-old woman with a history of stroke five months prior, bileaflet aortic valve prosthesis, hypertension, and insulin-dependent diabetes is admitted for laparoscopy with lysis of adhesions. The patient stopped her warfarin 10 days prior to admission and initiated enoxaparin five days later. When should the enoxaparin be discontinued?

Intra-operatively, the surgeon converted the case to an open laparotomy for a bowel resection with re-anastomosis; post-operatively, when should the hospitalist reinitiate warfarin and enoxaparin?

Background

Many patients receive chronic oral anticoagulant therapy to minimize their long-term risk of thromboembolic disease. Hospitalists and outpatient providers often care for such patients who need to undergo a medical procedure or operation. The risk of bleeding associated with the medical procedure necessitates an interruption in the patient’s chronic oral anticoagulant therapy. In this scenario, providers are faced with several therapeutic decisions:

  • How soon before the procedure should patients stop taking oral anticoagulant?
  • During the period of time when the patient is not taking chronic oral anticoagulant, should the patient receive parenteral bridging anticoagulant therapy?
  • After the procedure, when should patients restart chronic oral anticoagulant therapy?

‘Bridge’ anticoagulant therapy is the administration of a short-acting parenteral anticoagulant during the peri-operative period, when the patient is not taking chronic oral anticoagulant.1 The intent of bridge anticoagulant therapy is to minimize both the risk of thromboembolic events and the risk of bleeding during the peri-operative period. Bridging anticoagulant therapy is appropriate for some but not all patients undergoing medical procedures.

The Data

When to discontinue warfarin? Warfarin, the most commonly prescribed oral anticoagulant, achieves its therapeutic effects by antagonizing the actions of endogenous vitamin K-dependent coagulation factors. The decision on when to stop warfarin prior to surgery is dependent on the regeneration time of coagulation factors following the discontinuation of warfarin therapy. Although warfarin’s half-life is typically 36-42 hours, its therapeutic effects typically last up to five days in healthy subjects and often longer in elderly patients.2

Current guidelines recommend the discontinuation of warfarin at least five days prior to surgery (Grade 1C recommendation).3 Despite this recommendation, approximately 7% of patients will still have an international normalized ratio (INR) >1.5 after not taking warfarin for five days.4 For this reason, the guidelines recommend that all patients have their INR checked on the day of surgery. For those patients with an INR of 1.5 to 1.9 on the day prior to surgery, there is evidence to show that administration of 1 mg of vitamin K will lower the INR to 1.4 in greater than 90% of cases.5

Assessment of peri-procedural thrombotic risk. Knowledge of a patient’s past medical history is critical in helping providers stratify the patient’s peri-procedural thrombotic risk. According to the 2012 American College of Chest Physicians (ACCP) guidelines, a history of atrial fibrillation (Afib), mechanical heart valve(s), and previous VTE are independent risk factors for peri-procedural thrombotic events.3 Hospitalists may risk-stratify their patients based on the anticipated annualized rate of thrombosis or embolization: 15% for the respective low, medium, and high-risk groups.6

Patients with Afib history. For these patients, the CHADS2 score helps to stratify the risk of peri-procedural thrombosis. Low risk is defined as a CHADS2 score of zero to two, assuming that the two points were not scored for transient ischemic attack (TIA) or cerebrovascular accident (CVA). Any patient with a TIA or CVA within the previous three months is automatically considered high risk. Medium risk is a score of three or four.

FAQs

Why does warfarin have to be bridged?

The intent of bridge anticoagulant therapy is to minimize both the risk of thromboembolic events and the risk of bleeding during the peri-operative period. Bridging anticoagulant therapy is appropriate for some but not all patients undergoing medical procedures

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When starting a patient on warfarin How long should you bridge with heparin?

Therapeutic management of venous thromboembolism (VTE) (i.e. PE or DVT) with parenteral heparin anticoagulation should be overlapped with warfarin until the anticoagulant effect of warfarin is established (usually 5-6 days including at least 48 hours with the INR in the therapeutic range)

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How long do you bridge warfarin?

Bridging will begin 1 to 2 days after you stop warfarin. Warfarin is stopped about 4 to 5 days before your procedure or surgery. During this time, your blood levels of warfarin slowly drop. Bridging will be started again after your procedure or surgery, when it is safe.

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Why do you bridge warfarin with heparin?

Therefore, heparin is often used as a ?bridge? when initiating warfarin therapy in patients with AF, not only because physicians feel a need to begin anticoagulation as soon as possible for stroke prevention but also because they want to protect patients from this presumed transient hypercoagulable state

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Who should receive bridging anticoagulation?

Guidelines suggest that patients at high risk of thromboembolism receive bridging anticoagulation. This group includes patients with a CHADS2 score of 5 or 6, most patients with mechanical heart valves, and those with recent ischemic stroke or TIA, or recent deep vein thrombosis or pulmonary embolism (Box 2).

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What INR is too high for surgery?

Discuss with surgeon and anesthesiologist what the goal INR should be before surgery. Baseline INR is recommended in every case and this will guide further therapy. An INR < 1.5 is generally acceptable except for neurosurgery, ocular surgery and procedures requiring spinal anesthesia or epidural analgesia.

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How long does it take for INR to drop after stopping warfarin?

Almost all patients will achieve an international normalized ration (INR) of < 1.5 within 4 - 5 days of stopping warfarin,9 although patients with a higher (2.5 ? 3.5) target INR and the elderly (> 70 years) will require a longer period of warfarin withdrawal before surgery.

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How quickly does warfarin increase INR?

The anticoagulant and antithrombotic activity of warfarin depends on the clearance of functional clotting factors from the systemic circulation once the drug is administered (2, 3). The earliest changes in INR are typically seen 24 to 36 hours after administration of the dose.

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Why are enoxaparin and warfarin used together?

Enoxaparin injection is used together with warfarin to treat acute deep vein thrombosis with or without pulmonary embolism. It is also used to treat certain types of acute heart attacks.

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How do you manage high INR on warfarin?

Life-threatening bleeding and elevated INR: Hold warfarin therapy and give FFP WITH vitamin K 10 mg by slow IV infusion, repeated, if necessary depending on the INR.

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Can you take enoxaparin and warfarin together?

warfarin enoxaparin

Using warfarin together with enoxaparin may increase the risk of bleeding, including severe and sometimes fatal hemorrhage. Talk to your doctor if you have any questions or concerns.

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When should you not take enoxaparin?

You should not use enoxaparin if you are allergic to enoxaparin, heparin, benzyl alcohol, or pork products, or if you have: active or uncontrolled bleeding; or. if you had decreased platelets in your blood after testing positive for a certain antibody while using enoxaparin within the past 100 days.

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Does enoxaparin increase INR?

We demonstrate an increase in the INR for patients who received enoxaparin for post-operative VTE prophylaxis.

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Should warfarin and clexane be given together?

There is no interaction between these two medications if given at the same time. If you are taking Clexane once per day then, just like warfarin, take it in the same part of the day each time, ie. always in the morning, or always in the evening.

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When is the best time to give enoxaparin?

Adults?40 milligrams (mg) injected under the skin once a day for 7 to 10 days. The first dose should be given 2 hours before the surgery.

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Is enoxaparin better than warfarin?

After treatment D-dimer level and number of patients with high D-dimer diminished in both groups. Conclusion: Enoxaparin proved more effective than warfarin in the first treatment month. In the same safety and prophylactic effect enoxaparin is more effective in recanalization of occusions in the deep veins.

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Which Patients Should Receive Bridging Anticoagulation?

Which Patients Should Receive Bridging Anticoagulation? – The Hospitalist Case A 77-year-old woman with a history of stroke five months prior, bileaflet aortic valve prosthesis, hypertension, and insulin-dependent diabetes is admitted for laparoscopy with lysis of adhesions. The patient stopped her warfarin 10 days prior to admission and initiated enoxaparin five days later. When should the enoxaparin be discontinued? Intra-operatively, the surgeon converted the case to an open laparotomy for a bowel resection with re-anastomosis; post-operatively, when should the hospitalist reinitiate warfarin and enoxaparin? Background Many patients receive chronic oral anticoagulant therapy to minimize their long-term risk of thromboembolic disease. Hospitalists and outpatient providers often care for such patients who need to undergo a medical procedure or operation. The risk of bleeding associated with the medical procedure necessitates an interruption in the patient’s chronic oral anticoagulant therapy. In this scenario, providers are faced with several therapeutic decisions: How soon before the procedure should patients stop taking oral anticoagulant? During the period of time when the patient is not taking chronic oral anticoagulant, should the patient receive parenteral bridging anticoagulant therapy? After the procedure, when should patients restart chronic oral anticoagulant therapy? ‘Bridge’ anticoagulant therapy is the administration of a short-acting parenteral anticoagulant during the peri-operative period, when the patient is not taking chronic oral anticoagulant.1 The intent of bridge anticoagulant therapy is to minimize both the risk of thromboembolic events and the risk of bleeding during the peri-operative period. Bridging anticoagulant therapy is appropriate for some but not all patients undergoing medical procedures. The Data When to discontinue warfarin? Warfarin, the most commonly prescribed oral anticoagulant, achieves its therapeutic effects by antagonizing the actions of endogenous vitamin K-dependent coagulation factors. The decision on when to stop warfarin prior to surgery is dependent on the regeneration time of coagulation factors following the discontinuation of warfarin therapy. Although warfarin’s half-life is typically 36-42 hours, its therapeutic effects typically last up to five days in healthy subjects and often longer in elderly patients.2 Current guidelines recommend the discontinuation of warfarin at least five days prior to surgery (Grade 1C recommendation).3 Despite this recommendation, approximately 7% of patients will still have an international normalized ratio (INR) >1.5 after not taking warfarin for five days.4 For this reason, the guidelines recommend that all patients have their INR checked on the day of surgery. For those patients with an INR of 1.5 to 1.9 on the day prior to surgery, there is evidence to show that administration of 1 mg of vitamin K will lower the INR to 1.4 in greater than 90% of cases.5 Assessment of peri-procedural thrombotic risk. Knowledge of a patient’s past medical history is critical in helping providers stratify the patient’s peri-procedural thrombotic risk. According to the 2012 American College of Chest Physicians (ACCP) guidelines, a history of atrial fibrillation (Afib), mechanical heart valve(s), and previous VTE are independent risk factors for peri-procedural thrombotic events.3 Hospitalists may risk-stratify their patients based on the anticipated annualized rate of thrombosis or embolization: 15% for the respective low, medium, and high-risk groups.6 Patients with Afib history. For these patients, the CHADS2 score helps to stratify the risk of peri-procedural thrombosis. Low risk is defined as a CHADS2 score of zero to two, assuming that the two points were not scored for transient ischemic attack (TIA) or cerebrovascular accident (CVA). Any patient with a TIA or CVA within the previous three months is automatically considered high risk. Medium risk is a score of three or four.

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Bridging anticoagulation for interruption of warfarin in a patient …

Bridging anticoagulation for interruption of warfarin in a patient with atrial fibrillation Journal List CMAJ v.188(5); 2016 Mar 15 PMC4786390 CMAJ. 2016 Mar 15; 188(5): 361–362. A 78-year-old man with chronic nonvalvular atrial fibrillation presents to his family physician three weeks before a transurethral resection of the prostate for benign prostatic hypertrophy. His history includes hypertension and type 2 diabetes. He has no history of congestive heart failure, stroke or transient ischemic attack (TIA). His medications include warfarin, ramipril and metformin. He has a CHADS2 score of 3 and a CHA2DS2-VASc score of 4 (Box 1).1,2Box 1:Stratification for stroke risk in atrial fibrillation1,2The patient in this case has a CHADS2 score of 3. This risk score quantifies stroke risk in nonvalvular atrial fibrillation. By this scheme, his estimated annual risk of stroke is 5.9% (95% confidence interval 4.6%–7.3%).The patient’s CHA2DS2-VASc score is 4. This risk score attempts to improve the estimation of stroke risk, particularly at lower CHADS2 scores, by considering additional risk factors such as sex and the presence of vascular disease. By this score, his estimated annual risk of stroke (adjusted for warfarin use) is 4.0%.Should this patient’s anticoagulation be interrupted for surgery?Both the procedural bleeding risk and anesthetic plan affect the decision of whether to interrupt anticoagulation. Prospective observational studies and randomized trials have shown that continuing anticoagulants for most skin, dental and cataract procedures is safe.3 Patients undergoing pacemaker or defibrillator insertion experience less bleeding when warfarin is continued perioperatively than when bridging with heparin is used.4 However, procedures with a major bleeding risk, including abdominal, thoracic, orthopedic and urologic surgeries, require anticoagulant interruption.3 As such, temporary warfarin cessation is appropriate for this patient.Should bridging anticoagulation be used?Guidelines suggest warfarin be stopped about five days before a major procedure.3 Anticoagulation is resumed when the postoperative bleeding risk is diminished, with full therapeutic effect delayed five to seven days. Bridging anticoagulation is the use of heparin (typically low-molecular-weight heparin [LMWH]) to minimize time off anticoagulation and reduce the risk of thrombosis.Guidelines suggest that patients at high risk of thromboembolism receive bridging anticoagulation.3 This group includes patients with a CHADS2 score of 5 or 6, most patients with mechanical heart valves, and those with recent ischemic stroke or TIA, or recent deep vein thrombosis or pulmonary embolism (Box 2).3 However, a meta-analysis involving more than 12 000 patients suggested that bridging is associated with an increased risk of overall and major bleeding, with no improvement in stroke risk.5 Data from a prospective observational registry of more than 7000 US outpatients with atrial fibrillation also showed that patients undergoing anticoagulation bridging had more bleeding events, with a higher risk of arterial thromboembolism, hospital admission and death.6Box 2:Suggested risk stratification scheme for perioperative thromboembolism3Risk category (% annual risk of thromboembolism)Atrial fibrillationMechanical heart valveVenous thromboembolism (VTE)High (> 10%)CHADS2 score1 of 5 or 6; recent (within 3 mo) stroke or transient ischemic attack (TIA); rheumatic valvular heart diseaseAny mitral valve prosthesis; any caged-ball or tilting-disk aortic valve prosthesis; recent (within 6 mo) stroke or TIARecent (within 3 mo) VTE; severe thrombophilia (e.g., deficiency of protein C, protein S or antithrombin; antiphospholipid antibodies; multiple abnormalities)Moderate (5%–10%)CHADS2 score1 of 3 or 4Bi-leaflet aortic valve prosthesis and ≥ 1 risk factor (atrial fibrillation, prior stroke or TIA, hypertension, diabetes, congestive heart failure, age > 75 yr)VTE within past 3–12 mo; nonsevere thrombophilia (heterozygous factor V Leiden or prothrombin gene mutation); recurrent VTE; active…

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LMWH Bridging, Anticoagulation Clinic | UC San Diego Health

LMWH Bridging, Anticoagulation Clinic | UC San Diego Health‘Bridging” is a term that refers to the use of short-acting anticoagulants (heparin or LMWH) for a period of time during interruption of warfarin therapy when the INR is not within a therapeutic range. There is no established single bridging regimen.  Variability exists in the type of anticoagulant, intensity of anticoagulation and timing of perioperative administration.  In considering which regimen and administration approach to use, there are several points to consider: Anticoagulant intensity to prevent thromboembolism Proximity ot surgery of anticoagulant administration and risk for bleeding Dose of anticoagulant administration and risk for bleeding General recommendations: Stop therapeutic LMWH at least 24 hours prior to surgery Stop prophylactic LMWH at least 12 hours prior to surgery Resume LMWH once normal hemostasis is achieved (usually ~24-48 hours later) or based on thromboembolic risk (often evening of THA or TKA) See “Peri-Procedural Anticoagulation Recommendations” for more information. Reference: Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Throbosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141;e326S-e350S

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Bridging to Warfarin with Heparin in Atrial Fibrillation Isn't …

Bridging to Warfarin with Heparin in Atrial Fibrillation Isn’t Necessary, May Be HarmfulThe idea of bridging to warfarin using heparin or a low molecular weight heparin (LMWH, such as enoxaparin) is deeply engrained in pharmacy students and medical residents early in their education. Due to an initial prothrombotic state and a delayed onset of anticoagulation, warfarin is commonly “bridged” with parenteral anticoagulants until full anticoagulation is achieved. Among patients with atrial fibrillation with an elevated CHA2DS2-VASc score who are selected for warfarin, it seems logical to implement a heparin or LMWH “bridge” until an internal normalizing ratio (INR) goal of 2 to 3 is achieved; however, not only is this practice unnecessary, it may actually be harmful to patients.The Need for Bridging Warfarin in Patients with Venous Thromboembolism (VTE)When warfarin is used to treat an acute deep vein thrombosis (DVT) or pulmonary embolism (PE), a bridge with a parenteral anticoagulant is absolutely necessary for 2 reasons: Warfarin takes about 5 days to achieve full anticoagulation (INR above 2). During the first few days of warfarin therapy, patients are prothrombotic due to a decrease in protein C and S (natural anticoagulants) before thrombin levels diminish significantly.The necessity of warfarin bridging was best described in a 1992 article comparing heparin bridging versus no bridging among patients receiving warfarin for a DVT.1 Within the first 7 days of initiating warfarin, patients without a heparin bridge were much more likely to have an extension of their DVT or a new PE versus those with a bridge (39.6% vs 8.2%). On the basis of this trial, only 3 patients would need to receive a heparin bridge in order for one patient to not have a worsening of his or her DVT or experience a new PE.Warfarin Anticoagulation Among Patients with Atrial FibrillationIn atrial fibrillation, the 2014 AHA/ACC/HRS guidelines recommend either warfarin (class IA) or a DOAC (class IB) among patients with a CHA2DS2-VASc score of 2 or more.2 Among patients with atrial fibrillation, these anticoagulants are recommended to decrease the long-term risk of embolic stroke caused by blood stasis on the left side of the heart, primarily in the left atrium.The CHA2DS2-VASc scoring system provides an estimate of the risk of stroke or thrombotic embolism per year.3 For example, a CHA2DS2-VASc score of 2 correlates to a risk of approximately 2.2%, whereas the maximum score of 9 corresponds to an annual risk of 15.2%. If these risks were extrapolated to a 5-day period (the typical duration of warfarin onset), the risk is actually surprisingly small (0.03% to 0.2%). Given the very small risk of stroke during a 5-day period, the necessity of bridging to warfarin in patients with atrial fibrillation becomes more questionable.The 2014 Atrial Fibrillation Guidelines Don’t Provide Clear GuidanceThe 2014 atrial fibrillation guidelines recommend bridging to warfarin among patients with mechanical valves, but they provide little guidance for all other patients aside from emphasizing the balance between the risk of stroke and bleeding in the decision-making process.2 Given the paucity of data regarding the necessity to bridge to…

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