Bleeding perioperative discontinuation, bridging, and reversal of anticoagulation and antiplatelet therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The management of perioperative bleeding in the context of anticoagulation and antiplatelet therapy depends on the medication administered to the patient.

2013 ESA Guidelines for the Management of Severe Perioperative Bleeding (DO NOT EDIT)

Antiplatelet Agents

Class 1

"1. We recommend that aspirin therapy should continue perioperatively in most surgical settings, especially cardiac surgery. (Level of Evidence: C)"

"2. Where aspirin withdrawal is considered, we recommend a time interval of 5 days. (Level of Evidence: C)"

"3. Clopidogrel increases perioperative bleeding. In cases of increased bleeding risk, we recommend that it should be withdrawn for no more than 5 days. (Level of Evidence: C)"

"4. Prasugrel increases perioperative bleeding. In cases of increased bleeding risk, we recommend that it should be withdrawn for no more than 7 days. (Level of Evidence: C)"

"5. We recommend that antiplatelet agent therapy should resume as soon as possible postoperatively to prevent platelet activation. (Level of Evidence: C)"

"6. We recommend postponement of elective surgery following coronary stenting (at least 6 to 12 weeks for bare metal stent and one year for drug-eluting stents). (Level of Evidence: C)"

"7. We recommend that a multidisciplinary team meeting should decide on the perioperative use of antiplatelet agents in urgent and semi-urgent surgery. (Level of Evidence: C)"

Class 2

"1. For intra- or postoperative bleeding clearly related to aspirin, we suggest that platelet transfusion be considered (dose: 0.7 × 1011 [i.e. two standard concentrates] per 7 kg body weight in adults). (Level of Evidence: C)"

"2. We suggest that the first postoperative dose of clopidogrel or prasugrel should be given no later than 24 h after skin closure. We also suggest that this first dose should not be a loading dose. (Level of Evidence: C)"

"3. We suggest that urgent or semi-urgent surgery should be performed under aspirin/clopidogrel or aspirin/prasugrel combination therapy if possible, or at least under aspirin alone. (Level of Evidence: C)"

"4. We suggest that platelet transfusion should be considered (dose: 0.7 × 1011 [i.e. two standard concentrates] per 7 kg body weight in adults) in cases of intra- or postoperative bleeding clearly related to clopidogrel or prasugrel. (Level of Evidence: C)"

"5. According to pharmacological characteristics, we suggest that the management of ticagrelor may be comparable to clopidogrel (i.e. withdrawal interval of 5 days). (Level of Evidence: C)"

"6. Platelet transfusion may be ineffective for treating bleeding clearly related to ticagrelor when given 12 h before. (Level of Evidence: C)"

Heparin

Class 1

"1. We recommend that severe bleeding associated with intravenous unfractionated heparin (UFH) should be treated with intravenous protamine at a dose of 1 mg per 100 IU UFH given in the preceding 2–3 h. (Level of Evidence: A)"

Class 2

"1. We suggest that severe bleeding associated with subcutaneous UFH unresponsive to intravenous protamine at a dose of 1 mg per 100 IU UFH could be treated by continuous administration of intravenous protamine, with dose guided by aPTT. (Level of Evidence: C)"

"2. We suggest that severe bleeding related to subcutaneous low molecular weight heparin (LMWH) should be treated with intravenous protamine at a dose of 1 mg per 100 anti-Xa units of LMWH administered. (Level of Evidence: C)"

"3. We suggest that severe bleeding associated with subcutaneous LMWH and unresponsive to initial administration of protamine could be treated with a second dose of protamine (0.5 mg per 100 anti-FXa units of LMWH administered). (Level of Evidence: C)"

Fondaparinux

Class 2

"1. We suggest that the administration of rFVIIa could be considered to treat severe bleeding associated with subcutaneous administration of fondaparinux (off-label treatment). (Level of Evidence: C)"

Vitamin K Antagonists

Class 1

"1. We recommend that vitamin K antagonists (VKAs) should not be interrupted for skin surgery, dental and other oral procedures, gastric and colonic endoscopies (even if biopsy is scheduled, but not polypectomy), nor for most ophthalmic surgery (mainly anterior chamber, e.g. cataract), although vitreoretinal surgery is sometimes performed in VKA treated patients. (Level of Evidence: C)"

"2. We recommend that for low-risk patients (e.g. atrial fibrillation patients with CHADS2 score ≤2, patients treated for > 3 months for a non-recurrent VTE) undergoing procedures requiring INR <1.5, VKA should be stopped 5 days before surgery. No bridging therapy is needed. Measure INR on the day before surgery and give 5 mg oral vitamin K if INR exceeds 1.5. (Level of Evidence: C)"

"3. We recommend bridging therapy for high-risk patients (e.g. atrial fibrillation patients with a CHADS2 score > 2, patients with recurrent VTE treated for <3 months, patients with a mechanical valve). Day 5: last VKA dose; Day 4: no heparin; Days 3 and 2: therapeutic subcutaneous LMWH twice daily or subcutaneous UFH twice or thrice daily; Day 1: hospitalisation and INR measurement; Day 0: surgery. (Level of Evidence: C)"

"4. We recommend that for groups 1 and 2 above, VKAs should be restarted during the evening after the procedure. Subcutaneous LMWH should be given postoperatively until the target INR is observed in two measurements. (Level of Evidence: C)"

"5. We recommend that for group 3 above, heparin (UFH or LMWH) should be resumed 6–48 h after the procedure. VKA can restart when surgical hemostasis is achieved. (Level of Evidence: C)"

"6. We recommend that, in VKA treated patients undergoing an emergency procedure or developing a bleeding complication, [[Prothrombin complex concentrate|PCC]] (25 IU FIX/kg) should be given. (Level of Evidence: B)"

"7. We recommend to assess creatinine clearance in patients receiving NOAs and being scheduled for surgery. (Level of Evidence: B)"

New Oral Anticoagulants

Class 1

"1. We recommend that for low-risk patients (e.g. atrial fibrillation patients with CHADS2 score 2, patients treated for >3 months for a non-recurrent VTE) undergoing procedures requiring normal coagulation (normal diluted thrombin time or normal specific anti-FXa level), NOAs can be stopped 5 days before surgery. No bridging is needed. (Level of Evidence: C)"

Class 2

"1. We suggest that new oral anticoagulant agents (NOAs) should not be interrupted for skin surgery, dental and other oral procedures, gastric and colonic endoscopies (even if biopsy is scheduled, but not polypectomy), nor for most ophthalmic surgery, (mainly anterior chamber, e.g. cataract), although vitreoretinal surgery is sometimes performed in NOA treated patients. (Level of Evidence: C)"

"2. In patients treated with rivaroxaban, apixaban, edoxaban and in patients treated with dabigatran in which creatinine clearance is higher than 50 ml/min, we suggest bridging therapy for high-risk patients (e.g. atrial fibrillation patients with a CHADS2 score >2, patients with recurrent VTE treated for <3 months). Day 5: last NOA dose; Day 4: no heparin; Day 3: therapeutic dose of LMWH or UFH; Day 2: subcutaneous LMWH or UFH; Day 1: last injection of subcutaneous LMWH (in the morning, i.e. 24 h before the procedure) or subcutaneous UFH twice daily (i.e. last dose 12 h before the procedure), hospitalisation and measurement of diluted thrombin time or specific anti-FXa; Day 0: surgery. (Level of Evidence: C)"

"3. In patients treated with dabigatran with a creatinine clearance between 30 and 50 ml/min, we suggest to stop NOAs 5 days before surgery with no bridging. (Level of Evidence: C)"

"4. We suggest that for groups 2 and 3, heparin (UFH or LMWH) should be restarted 6–72 h after the procedure, taking the bleeding risk into account. NOAs may be resumed when surgical bleeding risk is under control. (Level of Evidence: C)"

Comorbidities Involving Hemostatic Derangement

Class 1

"1. We do not recommend discontinuation of Gingko biloba extracts. (Level of Evidence: B)"

Class 2

"1. We suggest that patients with hemostatic derangements associated with systemic, metabolic and endocrine diseases should be managed perioperatively in collaboration with a hematologist. (Level of Evidence: C)"

"2. We suggest that selective serotonin reuptake inhibitor (SSRI) treatment should not be routinely discontinued perioperatively. (Level of Evidence: B)"

"3. We suggest individualized perioperative discontinuation of antiepileptic agents, such as valproic acid, which may increase bleeding. (Level of Evidence: C)"

Sources

• 2013 ESA Guidelines for the Management of Severe Perioperative Bleeding