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xPlan Periprocedural Interruption and Bridging
Reference key concepts from the tools above
Quick ReferenceThe information in this app is based on content in the ACC’s Expert Consensus Decision Pathways. Refer to the Resources section for full references.
Anticoagulation Management Clinical Topic Collection
American Society for Gastrointestinal Endoscopy’s Standards of Practice Committee |
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American Society of Nephrology |
The risk stratification for the nephrology procedures was assigned based on the publications cited below and the following explanatory points:
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American Society of Regional Anesthesia and Pain Medicine |
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Interventional Section Leadership Council of the ACC |
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Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Gluckman TJ, Hucker W, Mehran R, Messé SR, Perino AC, Rodriguez F, Sarode R, Siegal D, Wiggins BS. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: a Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2020; Aug 76(5)594-622. DOI: 10.1016/j.jacc.2020.04.053
Doherty JU, Gluckman TJ, Hucker WJ, Januzzi Jr. JL, Ortel TL, Saxonhouse SJ, Spinler SA. 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation: A Report of the American College of Cardiology Expert Consensus Document Task Force. J Am Coll Cardiol 2017:69:871-898. DOI: 10.1016/j.jacc.2016.11.024
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October 2023
The app is meant for use by clinicians in relation to patients who are currently taking oral anticoagulants. Some parts of the app only apply to patients with nonvalvular AF, and this will be specified in those areas. The app applies to patients in the following situations:
The app is intended for use by clinicians to help navigate periprocedural planning and bleed management scenarios for patients on oral anticoagulants (OAC). The app is comprised of three tools to support the following clinical decisions:
To use the app:
The information and recommendations in this app are intended to support clinical decision making. They are not intended to represent the only or best course of care, or to replace clinical judgment. Therapeutic options should be determined after discussion between the patient and their care provider. While bleeding protocols at individual institutions may vary from the advice in this app, content in the app is derived from the referenced documents and is meant to represent ACC’s expert clinical opinion.
The information in this app was derived from the 2020 Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants and the 2017 Expert Consensus Decision Pathway on Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation. App content and design was refined and vetted by ACC member clinicians, and through user testing with clinicians practicing in relevant specialties. The app was developed as part of a continuing initiative to enable clinicians to access and implement ACC clinical policy at the point of care to improve quality, efficiency, and patient outcomes. The app is also part of ACC’s Anticoagulation Initiative, a comprehensive quality effort to improve care for patients on anticoagulation therapy.
Support for the app was provided by Boehringer Ingelheim, Daiichi Sankyo, Inc. and Janssen Pharmaceuticals, Inc. All content was independently developed with no sponsor involvement.
For Support
Call: (202) 375-6000, ext. 5603 or (800) 253-4636, ext. 5603
Email: membercare@acc.org
Indications for anticoagulation with high thrombotic risk
CHF: Congestive Heart Failure;TIA: Transient ischemic attackIndication | Patient characteristics |
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Mechanical valve prosthesis |
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Atrial fibrillation (AF) |
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Venous thromboembolism (VTE) |
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Prior thromboembolism with interruption of anticoagulation | Any |
Left ventricular or left atrial thrombus | Any |
Left ventricular assist device (LVAD) | Any |
In a life-threatening or critical site bleed, or in situations in which bleeding cannot be controlled with other measures, reversal of OACs may be required. This section provides guidance for administering reversal/hemostatic agents.
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Reversal Stratergy | Dosage | |
4F-PCC† | Note regarding vitamin K: When PCCs are used to reverse VKAs, vitamin K should always be given. If bleed is considered major: Administer 5-10 mg IV vitamin K If bleed is considered nonmajor: Administer 2-5 mg PO/IV vitamin K |
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• INR 2 to < 4 | 25 units/kg | |
• INR 4-6 | 35 units/kg | |
• INR >6 | 50 units/kg | |
4F-PCC low fixed-dose option | 1000 units for any non-intractional major bleed | |
1500 units for intrational hemorrhage | ||
If 4F-PCC not available, administer plasma | 10-15 mL/kg (1) |
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Reversal Stratergy | Dosage |
Idarucizumab | 5g idarucizumab IV ‡ |
If idarucizumab is not available, administer either PCC or aPCC | 50 units/kg IV § |
Consider activated charcoal for known recent ingestion (within 2-4 h) | (n/a) |
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Reversal Stratergy | Dosage |
Off-label treatment with andexanet alfa II ¶ | Initial IV Bolus 800 mg at a target rate of 30 mg/min, follow-up IV infusion 8 mg/min for up to 120 minutes |
If andexanet alfa is not available, administer PCC or aPCC | 50 units/kg IV § |
Consider activated charcoal for known recent ingestion (within 2-4 h) | (n/a) |
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Reversal Stratergy | Dosage | ||||
Andexanet alfa"¶ | Last dose of apixaban | Timing of last dose | Low/High | Initial IV Bolus | Follow-On IV Infusion |
≤ 5 mg | < 8 hours or unknown | Low dose | 400 mg at a target rate of 30 mg/min | 4 mg/min for up to 120 minutes | |
≥ 8 hours or unknown | Low dose | 400 mg at a target rate of 30 mg/min | 4 mg/min for up to 120 minutes | ||
> 5 mg or unknown | < 8 hours or unknown | High dose | 800 mg at a target rate of 30 mg/min | 8 mg/min for up to 120 minutes | |
≥ 8 hours | Low dose | 400 mg at a target rate of 30 mg/min | 4 mg/min for up to 120 minutes | ||
If andexanet alfa is not available, administer PCC or aPCC | 50 units/kg IV§ | ||||
Consider activated charcoal for known recent ingestion (within 2-4 h) | n/a |
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Reversal Stratergy | Dosage | ||||
Andexanet alfa"¶ | Last dose of rivaroxaban | Timing of last dose | Low/High | Initial IV Bolus | Follow-On IV Infusion |
≤ 10 mg | < 8 hours or unknown | Low dose | 400 mg at a target rate of 30 mg/min | 4 mg/min for up to 120 minutes | |
≥ 8 hours or unknown | Low dose | 400 mg at a target rate of 30 mg/min | 4 mg/min for up to 120 minutes | ||
> 10 mg or unknown | < 8 hours or unknown | High dose | 800 mg at a target rate of 30 mg/min | 8 mg/min for up to 120 minutes | |
≥ 8 hours | Low dose | 400 mg at a target rate of 30 mg/min | 4 mg/min for up to 120 minutes | ||
If andexanet alfa is not available, administer PCC or aPCC | 50 units/kg IV§ | ||||
Consider activated charcoal for known recent ingestion (within 2-4 h) | n/a |
4F-PCC = four-factor prothrombin complex concentrate; aPCC = activated prothrombin complex concentrate; h = hours; IV = intravenous; PCC = prothrombin complex concentrate; INR = international normalized ratio
*Reversal/hemostatic agents include repletion strategies such as PCCs, plasma, vitamin K, and specific reversal agents for DOACs (e.g., idarucizumab for dabigatran; andexanet alfa for apixaban or rivaroxaban).
† When PCCs are used to reverse vitamin K antagonists, vitamin K should also always be given.
‡ If bleeding persists after reversal and there is laboratory evidence of a persistent dabigatran effect, or if there is concern for a persistent anticoagulant effect before a second invasive procedure, a second dose of idarucizumab may be reasonable.
§ Refer to prescribing information for max units. To control bleeding in hemophilia patients with inhibitors, aPCC is typically administered intravenously in doses ranging from 50 U/kg to 100 U/kg, with a daily maximum of 200 U/kg. There are no randomized data regarding dosing in patients with factor Xa inhibitor–related major bleeding. Based on preclinical evidence, case reports, and case series data, an initial intravenous dose of 50 U/kg is suggested for patients with FXa inhibitor major bleeding and who are known or likely to have clinically significant anticoagulant levels.
II ANNEXA-4 full report excluded patients with DOAC levels <75 ng/ml because those patients were considered to have clinically insufficient levels for reversal agent. If drug effect/level can be assessed without compromising urgent clinical care decisions, then assessment should be performed before andexanet alfa is administered.
¶ Andexanet alfa is not currently available at every institution; please refer to product locator on manufacturer’s website.
(1) Sarode R, Milling TJ, Jr., Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma controlled, phase IIIb study. Circulation. 2013; 128:1234-43.
Drug | Suggested Test |
Dabigatran |
• Liquid chromatography-tandem mass spectrometry • Dilute thrombin time • Ecarin clotting time • Ecarin chromogenic assay |
Apixaban, betrixaban, edoxaban, or rivaroxaban | • Liquid chromatography-tandem mass spectrometry • Anti–FXa * |
*Useful for quantitation of plasma drug levels only when calibrated with the drug of interest DOAC = direct-acting oral anticoagulant; FXa = factor-Xa
Exclude Clinically Relevant* Drug Levels |
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Suggested Test:
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Interpretation:
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Determine Whether On-Therapy or Above On-Therapy Levels are Present |
Suggested Test:
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Interpretation:
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Exclude Clinically Relevant* Drug Levels |
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Suggested Tests:
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Interpretation:
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Determine Whether On-Therapy or Above On-Therapy Levels are Present. |
Suggested Test:
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Interpretation:
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Exclude Clinically Relevant* Drug Levels |
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Suggested Test:
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Interpretation:
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Determine Whether On-Therapy or Above On-Therapy Levels are Present |
Suggested Test:
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Interpretation:
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*The term “clinically relevant” refers to DOAC levels that may contribute to bleeding or surgical bleeding risk. The minimum DOAC level that may contribute to bleeding or surgical bleeding risk is unknown. The International Society on Thrombosis and Hemostasis recommends consideration of anticoagulant reversal for patients with serious bleeding and a DOAC level >50 ng/mL, and for patients requiring an invasive procedure with high bleeding risk and a DOAC level >30 ng/mL.
aPTT = activated partial thromboplastin time; DOAC = direct-acting oral anticoagulant; FXa = factor Xa; LMWH = low-molecular-weight heparin; PT = prothrombin time; TT = thrombin time; UFH = unfractionated heparin.
CrCl mL/Min |
≥80 | 50–79 | 30-49 | 15-29 | <15 | ≥30 | 15-29 | <15 |
Estimated drug half-life, h | 13 | 15 | 18 | 27 | 30 (off dialysis) |
• Apixaban, betrixaban, rivaroxaban: 6–15 • Betrixaban:19-27 |
• Apixaban: 17 • Edoxaban: 17 • Rivaroxaban: 9 |
• Apixaban: 17 (off dialysis) • Edoxaban: 10-17 (off dialysis) • Rivaroxaban: 13 (off dialysis) |
CrCl = creatinine clearance
CrCl mL/Min |
≥80 | 50–79 | 30-49 | 15-29 | <15 | ≥30 | 15-29 | <15 |
Low | ≥24 h | ≥36 h | ≥48 h | ≥72 h | No data. Consider measuring dTT and/or withholding ≥96 h. | ≥24 h | ≥36 h | No data. Consider measuring agent- specific anti-Xa level and/or withholding ≥48 h. |
Uncertain, intermediate, or high | ≥48 h | ≥72 h | ≥96 h | ≥120 h | No data. Consider measuring dTT | 48 h | No data. Consider measuring agent-specific anti-Xa level and/or withholding ≥72 h. |
NOTE: The duration for withholding is based upon the estimated DOAC half-life withholding times of 2 to 3 half-lives for low procedural bleeding risk and 4 to 5 drug half-lives for uncertain, intermediate, or high procedural bleeding risk
CrCl = creatinine clearance; DOAC = direct-acting oral anticoagulant; dTT = dilute thrombin time.
Type of Bleed | Initial Signs and Symptoms | Potential Consequences of Bleed |
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Intracranial hemorrhage: Includes intraparenchymal, subdural, epidural, and subarachnoid hemorrhages | Unusually intense headache, emesis
reduced or loss of consciousness, vision changes, numbness, weakness, aphasia, ataxia, vertigo, seizures |
Stupor or coma Permanent neurological deficit Death |
Other central nervous system hemorrhage: Includes intraocular, intra- or extra- axial spinal hemorrhages | Intraocular: monocular eye pain, vision changes, blindness
Spinal: back pain, bilateral extremity weakness or numbness, bowel or bladder dysfunction, respiratory failure |
Intraocular: permanent vision loss
Spinal: permanent disability, paraplegia, quadriplegia, death |
Pericardial tamponade | Shortness of breath, tachypnea, hypotension, paradoxical pulse, jugular venous distension, tachycardia, muffed heart sounds, rub | Cardiogenic shock Death |
Airway: includes posterior epistaxis | Airway: hemoptysis, shortness of breath, hypoxia
Posterior epistaxis: profuse epistaxis, hemoptysis, hypoxia, shortness of breath |
Hypoxemic respiratory failure Death |
Hemothorax, intra-abdominal bleeding, and retroperitoneal hemorrhage |
Hemothorax: tachypnea, tachycardia, hypotension, decreased breath sounds Intra-abdominal (nongastrointestinal): abdominal pain, distension, hypotension, tachycardia Retroperitoneal hemorrhage:back/flank/hip pain, tachycardia, hypotension |
Hemothorax: respiratory failure
Retroperitoneal hemorrhage: femoral neuropathy All: hypovolemic shock, death |
Extremity bleeds: Includes intramuscular and intra-articular bleeding | Intramuscular: pain, swelling, pallor, paresthesia, weakness, diminished pulse
Intra-articular: joint pain, swelling, decreased range of motion |
Intramuscular: compartment syndrome, paralysis, limb loss
Intra-articular: irreversible joint damage |
After a bleeding event, the indication for OAC should be reassessed to determine whether continued therapy is warranted based on established clinical practice guidelines. A risk-benefit assessment should be conducted in consultation with other practitioners and in discussion with patients or caregivers. The below information includes points to consider in determining the appropriateness of restarting anticoagulation.
The following are possible conditions for which OAC may no longer be indicated:
Patients who are at high thrombotic risk will likely benefit from restarting anticoagulation, even if the risk of rebleeding is high. In general, conditions with high thrombotic risk favor early reinitiation of anticoagulation once hemostasis is achieved and the patient is clinically stable.
Indication | Patient Characteristics |
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Mechanical valve prosthesis with or without AF* |
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Nonvalvular AF† |
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Valvular AF (with moderate or greater mitral stenosis or a mechanical valve prosthesis)* | |
VTE† |
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Prior thromboembolism with interruption of anticoagulation | |
Left ventricular thrombus§ |
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Left atrial thrombus | |
Left ventricular assist device§ |
*Currently, only warfarin is indicated for patients ready to restart their anticoagulation.
†Patients can resume any OAC when ready to restart their anticoagulation.
‡For patients with CHA2DS2-VASc scores of 4, the annual rate of thromboembolism is 4% (2.8-5.4%).
§Currently, only conventional-intensity warfarin therapy is indicated for patients ready to restart their anticoagulation.
AF = atrial fibrillation; CHA2DS2-VASc = Congestive heart failure, Hypertension, Age ( >65 = 1 point, ≥75 = 2 points), Diabetes, previous Stroke/transient ischemic attack (2 points); HF = heart failure; LV = left ventricular; MI = myocardial infarction; TIA = transient ischemic attack; VTE = venous thromboembolism.
The below definitions for thrombotic risk have been taken from the 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation. They have been defined in relation to this document, and may not be considered as standard accepted definitions.
Low | CHA2DS2-VASc 1-4 (annualized stroke risk <5%), no prior TE |
Moderate | CHA2DS2-VASc 5-6 (annualized stroke risk 5-10%) or prior TE more than 3 months previously |
High | CHA2DS2-VASc 7+ (annualized stroke risk >10%) or prior TE within 3 months |
Optimal patient engagement in the decision to restart anticoagulation involves shared decision making with patients and care providers. Discussions should include the risks of bleeding that come with resuming anticoagulation, including clinical signs of bleeding, implications of thrombotic events, and death without anticoagulation.
Factors to Consider | Discussion Points |
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Timing |
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Associated Risks |
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Associated benefits |
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Please use the below links to access complete prescribing information for drugs referenced in this app.