Hospital Medicine

Anti-coagulation in the pre/perioperative period

I. Problem/Challenge.

Many patients who are on an antithrombotic medication eventually face the need for an operation or invasive procedure.

The perioperative risk of increased bleeding and its complications may outweigh the thromboembolic risk of an interruption in their anticoagulant medications. Cardioembolic stroke or arterial thromboembolism frequently leads to major disability and has a high mortality rate. Prosthetic valve thrombosis carries extremely high morbidity and mortality rates. Venous thromboembolism (VTE) perioperatively can also be devastating.

On the other hand, intraoperative or postoperative hemorrhage can lead to organ damage, wound infection or death. Balancing these risks is usually a complex endeavor. Physicians may lack consensus in preferences for perioperative anticoagulation, and there is often minimal evidence that applies to an individual patient undergoing a particular procedure.

II. Identify the Goal Behavior

The health care provider must decide whether to interrupt anticoagulants prior to a planned procedure, and if so, when to stop them, when to restart them, and whether to bridge the interruption with a shorter acting antithrombotic.

Considerations should include patient-related risks, the indication for anticoagulation, procedure-related risks, available evidence, recommendations of the surgeon or provider performing the procedure, and pertinent patient preferences. If the patient is not known to the provider, a complete history and physical is warranted. The patient's prior tolerance of procedures and periprocedural bleeding with or without anticoagulants will be of interest. The provider should know the timing and type of procedure planned.

Find out from the surgeon or provider performing the procedure if he or she has certain concerns regarding anticoagulants. Determine what is known about the bleeding risk of the procedure. Ensure thromboembolic and bleeding risks are adequately conveyed to the patient and that his or her concerns are addressed. It is ideal for the patient to be re-evaluated during the postoperative period as the plan may need to change based on unexpected outcomes.

III. Describe a Step-by-Step approach/method to this problem.

Managing patients on antiplatelets:

  • Is the patient undergoing a percutaneous coronary intervention (PCI)?

    • An antiplatelet should typically be continued prior to a PCI.

    • If clopidogrel is interrupted, a loading dose should be given prior to PCI if possible.

  • Is the patient on aspirin alone?

    • For patients with prior distant PCI (ie, greater than 1 year following a drug-eluting stent, and greater than 6 weeks of a bare metal stent), it is appropriate to continue aspirin perioperatively. Some surgeries, such as spinal surgery, may be exceptions, highlighting the importance of discussion with the surgeon.

    • For all other patients, the POISE-2 trial demonstrated lack of efficacy for perioperative aspirin but demonstrated increased bleeding risk, so aspirin is generally stopped pre-operatively in these patients. Aspirin should be stopped 7-10 days prior to surgery and restarted the day after surgery if hemostasis is attained.

  • Is the patient on dual antiplatelet therapy with aspirin and a thienopyridine, such as clopidogrel, prasugrel, or ticlopidine for a coronary stent?

    • For patients with a new coronary stents (ie, a bare metal stent placed within 6 weeks or a drug-eluting stent placed within a year), management of antiplatelet agents is complicated, as interruption of dual antiplatelet therapy raises the risk of thrombotic complications. For patients undergoing non-urgent noncardiac surgery, it is generally deferred until after a year after placement of the bare metal or drug eluting stent. However, the greatest risk is during the first 6 months and it is generally recommended to wait, if at all possible, until 6 months after placement for surgery. Physicians should consider delaying elective procedures during this time. Should urgent surgery be considered during this time period, an interdisciplinary conversation with a cardiologist and the surgeon regarding the bleeding risk of the procedure and the risk of thrombotic complications is recommended, and this risk-benefit balance should be discussed with the patient.

    • For patients with more distant coronary stents (bare metal stents placed greater than 6 weeks ago or drug-eluting stents placed greater than 1 year ago), the thienopyridine can be stopped and aspirin continued perioperatively for most patients. Clopidogrel should be stopped 5-7 days prior to surgery. It may be restarted the day after surgery if hemostasis is attained.

      More data is available for clopidogrel than the other drugs in its class. Similar reasoning may apply to prasugrel and ticlopidine, but since ticlopidine may have more prolonged antiplatelet effects, consideration may be given to an earlier preoperative discontinuation time for this drug where appropriate.

  • Is there excessive perioperative bleeding in the setting of antiplatelet usage?

    • Platelet transfusion may be considered in the setting of excessive bleeding when antiplatelets are still in effect, such as when the urgency of a procedure prevents their early discontinuation.

    • Continued close monitoring in an appropriate setting will be necessary.

Managing patients on anticoagulants

Step 1: Determine the urgency of the procedure.

  • Before an emergent or urgent invasive procedure, patients may be given vitamin K orally or subcutaneously (intravenous route preserved for emergencies) if taking vitamin K antagonists. If the procedure is emergent, patients may also receive fresh-frozen plasma (FFP) or another prothrombin concentrate.

  • For patients taking dabigatran, anti-fibrinolytic agents can be given. For life-threatening bleeding, idarucizumab is a recently approved reversal agent. Activated prothrombin complex concentrate (aPCC) is also available for life-threatening bleeding events.

  • At this time, there are no approved reversal products for rivaroxaban, apixaban, or edoxaban. Anti-fibrinolytic agents can be given along with 4-factor PCC.

  • Adnexanet alpha is like to be FDA-approved soon but has not been approved at the time of this writing. This agent reverses the anti-factor Xa effect of rivaroxaban and edoxaban.

Step 2: Estimate the risk of major bleeding associated with the procedure.

  • There is no validated method to stratify procedures according to bleeding risk.

  • Consultation about the bleeding risk with the surgeon or physician performing the procedure may be helpful, as he or she may have specific requirements (e.g. will not operate until the international normalized ratio (INR) is below a certain level).

  • The following surgeries are usually considered to be of high risk of excessive bleeding: coronary artery bypass surgery, heart valve replacement, major vascular surgery such as aortic aneurysm repair or peripheral artery bypass surgery, intracranial or spinal surgery, major orthopedic surgery such as large joint replacement, prostate or bladder surgery, major cancer surgery, and reconstructive plastic surgery.

  • The following surgeries are generally considered low risk for bleeding: Cataract surgeries and many dermatologic procedures.

  • All other procedures are generally considered to be of average bleeding risk. It is always helpful to discuss bleeding risk with the surgeon prior to performing a pre-operative assessment.

  • Procedures that may pose a substantial risk of bleeding or hematoma include: biopsies of highly vascular tissues (such as the kidney or prostate), cardiac pacemaker or defibrillator implantation and resection of some colon polyps such as sessile polyps greater than 2 centimeters (cm) in diameter.

Step 3: Determine the patient's thromboembolic risk in the absence of their anticoagulants.

  • Does the patient have atrial fibrillation?

    • High-risk patients include those with a CHADS2 (congestive heart failure, hypertension, age greater than or equal to 75 years, diabetes mellitus, prior stroke or transient ischemic attack (TIA)) score of 5 or 6, stroke or TIA within 3 months, or rheumatic heart disease.

    • Moderate risk patients include those with a CHADS2 score of 3 or 4 or a remote stroke or TIA.

    • Low risk patients include those with a CHADS2 score of 0 to 2 without a history of stroke or TIA.

  • Does the patient have a mechanical heart valve?

    • High-risk patients include those with a mitral valve prosthesis, an older prosthetic aortic valve (such as a caged ball or tilting disc valve), or a stroke or TIA within 6 months.

    • Moderate risk patients include those with a bileaflet aortic valve prosthesis plus one of the following: history of stroke/TIA, atrial fibrillation, heart failure, hypertension, diabetes, or aged over 75 years.

    • Low risk patients include those with a bileaflet aortic valve prosthesis without a history of stroke/TIA or stroke risk factors listed above.

  • Does the patient have a history of a VTE?

    • High-risk patients include those with a VTE within 3 months or with severe thrombophilia (such as protein C or S deficiency, antithrombin deficiency, or antiphospholipid antibodies).

    • Moderate risk patients include those with a VTE in the past 3-12 months, recurrent VTE, active cancer (such as receiving treatment within 6 months or palliation), or with less severe thrombophilia (such as heterozygous factor V Leiden mutation or heterozygous factor II mutation).

    • Low risk patients include those with only a single VTE that occurred over a year ago.

Step 4: Weigh risks and benefits to recommend a possible interruption in antithrombotic therapy and whether bridging is necessary.

  • How to manage vitamin K antagonists (VKAs)

    • VKAs should be stopped at least 5 days prior to the procedure if normalization of the INR is required.

    • Low dose (1-2mg) oral vitamin K may be given to patients who still have an elevated INR just prior to surgery.

    • VKAs may be restarted 12-24 hours postoperatively if hemostasis is attained.

  • How to manage Direct Oral Anticoagulants (DOACs, otherwise known as Novel Oral Anticoagulants): Typically bridging is NOT required for these agents given their short half-life. Longer periods of interruption should be considered in consultation with the surgeon for neurosurgical procedures or other procedures of excessive bleeding risk.

    • Dabigatran: This direct thrombin inhibitor can be stopped 1 day prior to a minor procedure and 2-3 days prior to a major surgical procedure if renal function is normal, and stopped 3-5 days for patients with CrCl< 30-50 milliliters/minute). Within each recommended window, consider longer cessation of anticoagulation for higher bleeding-risk procedures or where the consequences of bleeding would be severe (e.g., neurosurgery).

    • Rivaroxaban, apixaban, and edoxaban: These direct factor Xa inhibitors can be stopped 2-3 days prior to a procedure. The longer end of this window is reserved for patients undergoing high bleeding risk procedures.

  • Whether to use bridge therapy

    • For atrial fibrillation:

      • High risk for thromboembolism: Bridging with parenteral anticoagulation (unfractionated heparin [UFH] or low molecular weight heparin [LMWH]) is recommended.

      • Intermediate risk for thromboembolism: Based on recent data (the BRIDGE study), bridging is not recommended for this group due to lack of efficacy and increased bleeding risk.

      • Low risk for thromboembolism – no bridging required.

    • For venous thromboembolism:

      • The risk of recurrent VTE is highest with in the first month following the index VTE, and for patients requiring urgent surgery within the first month following a VTE, both pre- and post-operative bridging is recommended.

      • For patients 1-3 months after an episode of acute VTE, post-operative bridging is recommended. Pre-operative bridging in this group can be considered.

    • For prosthetic heart valves:

      • Patients at high risk of thromboembolism (defined above as mitral valve prostheses, older prosthetic aortic valves, or patients with recent stroke/TIA) should be bridged pre- and post-operatively.

      • Bridging should also be considered for patients at intermediate risk for thromboembolism.

  • How to use bridge therapy

    • Consider outpatient use of subcutanous LMWH, as it incurs less cost than intravenous (IV) UFH in an inpatient setting.

    • If LMWH is used, administer the twice daily dosing regimen and give the last dose about 24 hours prior to the procedure.

    • If IV UFH is used, stop the infusion about four hours prior to the procedure.

    • LMWH or IV UFH may be restarted the day after the procedure with a lower bleeding risk if hemostasis is attained. For major surgery, restart parenteral anticoagulation 48-72 hours after the surgery.

Step 5: Continue to monitor the patient pre- and postoperatively to address antithrombotic decisions based on ongoing blood loss or increases in thromboembolic risk (e.g. after spinal or major orthopedic surgery).

IV. Common Pitfalls

Medical decisions are often made without seeking the patient's input. Involve the patient when possible to discover his or her personal values or requests. For example, a patient may want you to do anything possible to prevent a stroke, and be willing to accept increased risks of excessive bleeding. A patient who would not want blood products may be willing to accept a higher thromboembolic risk to avoid an increased risk of bleeding.

Hospitalists may encounter patients referred for pre-operative assessment very close to a previously scheduled procedure without sufficient time to implement changes to anticoagulants. In individual cases, it may be appropriate to delay a procedure in order to have time to reduce perioperative risks of bleeding or thromboembolic events.

If the provider managing anticoagulation is a consultant, he or she should not "sign off the case" too early. Monitoring for postoperative bleeding or thrombosis and optimizing timing and type of prophylactic treatment can prevent complications.

If the patient is already seeing another provider who has contributed to the patient's antithrombotic treatment in the past (such as a haematologist or pulmonologist), consider consulting with this provider pre-operatively. There may be details of the patient's past surgical or thromboembolic history that will be pertinent to the current decision-making.

V. National Standards, Core Indicators and Quality Measures.

The recommendations from the 9th edition of the American College of Chest Physicians (ACCP) guidelines for the perioperative management of antithrombotic therapy are largely represented in this article.

The American College of Cardiology/American Heart Association (ACC/AHA) has not published specific guidelines on perioperative antithrombotic management.

The ACCP guidelines include a summary and review of pertinent studies through 2010.

The best evidence for the peri-operative management of warfarin for patients with atrial fibrillation comes from the BRIDGE study. This large randomized trial found no benefit and increased bleeding for patients bridged with peri-operative low-molecular-weight heparin.

Management of perioperative aspirin therapy was changed by the POISE-2 trial, which found no benefit but increased bleeding for perioperative aspirin use.

IV. What's the evidence?

Douketis, JK, Spyropoulos, AC, Kaatz, S. "Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation". New Engl J Med. vol. 373. 2015. pp. 823-33.

Devereaux, PJ, Mkrobada, M, Sessler, DI. "Aspirin in Patient Undergoing Noncardiac Surgery". N Engl J Med. vol. 370. 2014. pp. 1494-1503.

Douketis, JD, Berger, PB, Spencer, FA. "Perioperative management of antithrombotic therapy. American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition)". Chest. vol. 141. 2012 Feb. pp. e326S-e350s.

Faltas, B, Kouides, PA. "Update on perioperative bridging in patients on chronic oral anticoagulation". Expert Review of Cardiovascular Therapy. vol. 7. 2009. pp. 1533-1539.

Kraai, EP, Lopes, RD, Alexander, JH. "Perioperative management of anticoagulation: guidelines translated for the clinician". Journal of Thrombosis and Thrombolysis. vol. 28. 2009. pp. 16-22.

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