Perioperative bleeding

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

Synonyms and keywords: perioperative hemorrhage

Overview

Excessive perioperative bleeding is a major complication following surgery and is associated with increased morbidity and mortality. Common causes include inherited bleeding diathesis or platelet disorders, major surgical procedures, and coagulation abnormalities related to certain conditions (eg, uremia, liver failure, sepsis) and medications.

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

Evaluation of Coagulation Status

Class 1

"1. We recommend the use of a structured patient interview or questionnaire before surgery or invasive procedures, which considers clinical and family bleeding history and detailed information on the patient’s medication. (Level of Evidence: C) "

"2. We recommend the use of standardized questionnaires on bleeding and drug history as preferable to the routine use of conventional coagulation screening tests such as aPTT, PT and platelet count in elective surgery. (Level of Evidence: C) "

"3. We recommend the application of transfusion algorithms incorporating predefined intervention triggers to guide hemostatic intervention during intraoperative bleeding. (Level of Evidence: B) "

"4. We recommend the application of transfusion algorithms incorporating predefined intervention triggers based on point-of-care (POC) coagulation monitoring assays to guide hemostatic intervention during cardiovascular surgery. (Level of Evidence: C) "

Evaluation of Platelet Function

Class 2

"1. We suggest preoperative platelet function testing only in addition to a positive bleeding anamnesis. (Level of Evidence: C) "

"2. We suggest that preoperative platelet function testing be used to identify decreased platelet function caused by medical conditions and antiplatelet medication. (Level of Evidence: C) "

Preoperative Correction of Anemia

Class 1

"1. We recommend that patients at risk of bleeding are assessed for anemia 4–8 weeks before surgery. (Level of Evidence: C) "

"2. If anemia is present, we recommend identifying the cause (iron deficiency, renal deficiency or inflammation). (Level of Evidence: C) "

"3. We recommend treating iron deficiency with iron supplementation (oral or intravenous). (Level of Evidence: B) "

Class 2

"1. If iron deficiency has been ruled out, we suggest treating anemia patients with erythropoietin-stimulating agents. (Level of Evidence: A) "

"2. If autologous blood donation is performed, we suggest treatment with erythropoietin-stimulating agents in order to avoid preoperative anemia and increased overall transfusion rates. (Level of Evidence: B) "

Optimizing Macrocirculation

Class 1

"1. We recommend aggressive and timely stabilization of cardiac preload throughout the surgical procedure, as this appears beneficial to the patient. (Level of Evidence: B) "

"2. We recommend the avoidance of hypervolemia with crystalloids or colloids to a level exceeding the interstitial space in steady state, and beyond an optimal cardiac preload. (Level of Evidence: B) "

"3. We recommend against the use of central venous pressure and pulmonary artery occlusion pressure as the only variables to guide fluid therapy and optimize preload during severe bleeding; dynamic assessment of fluid responsiveness and non-invasive measurement of cardiac output should be considered instead. (Level of Evidence: B) "

Class 2

"1. We suggest the replacement of extracellular fluid losses with isotonic crystalloids in a timely and protocol-based manner. (Level of Evidence: C) "

"2. We suggest the use of balanced solutions for crystalloids and as a basic solute for iso-oncotic preparations. (Level of Evidence: C) "

Transfusion Triggers

Class 1

"1. We recommend a target haemoglobin concentration of 7–9g dl-1 during active bleeding. (Level of Evidence: C) "

Oxygen Fraction

Class 1

"1. We recommend that inspiratory oxygen fraction should be high enough to prevent arterial hypoxaemia in bleeding patients, while avoiding extensive hyperoxia (PaO2>26.7 kPa [200 mmHg]). (Level of Evidence: C) "

Monitoring Tissue Perfusion

Class 1

"1. We recommend repeated measurements of a combination of hematocrit/hemoglobin, serum lactate, and base deficit in order to monitor tissue perfusion, tissue oxygenation and the dynamics of blood loss during acute bleeding. These parameters can be extended by measurement of cardiac output, dynamic parameters of volume status (e.g. stroke volume variation, pulse pressure variation) and central venous oxygen saturation. (Level of Evidence: C) "

Transfusion of Labile Blood Products

Class 1

"1. We recommend that all countries implement national hemovigilance quality systems. (Level of Evidence: C) "

"2. We recommend a restrictive transfusion strategy which is beneficial in reducing exposure to allogeneic blood products. (Level of Evidence: A) "

"3. We recommend photochemical pathogen inactivation with amotosalen and UVA light for platelets. (Level of Evidence: C) "

"4. We recommend that labile blood components used for transfusion are leukodepleted. (Level of Evidence: B) "

"5. We recommend that blood services implement standard operating procedures for patient identification and that staff be trained in early recognition of, and prompt response to, transfusion reactions. (Level of Evidence: C) "

"6. We recommend that multiparous women be excluded from donating blood for the preparation of FFP and for the suspension of platelets in order to reduce the incidence of transfusion-related acute lung injury. (Level of Evidence: C) "

"7. We recommend that all RBC, platelet and granulocyte donations from first-or second-degree relatives be irradiated even if the recipient is immunocompetent, and all RBC, platelet and that granulocyte products be irradiated before transfusing to at-risk patients. (Level of Evidence: C) "

"8. We recommend the transfusion of leukocyte-reduced RBC components for cardiac surgery patients. (Level of Evidence: a) "

Cell Salvage

Class 1

"1. We recommend the routine use of red cell salvage which is helpful for blood conservation in cardiac operations using CPB. (Level of Evidence: A) "

"2. We recommend against the routine use of intraoperative platelet-rich plasmapheresis for blood conservation during cardiac operations using CPB. (Level of Evidence: A) "

"3. We recommend the use of red cell salvage in major orthopedic surgery because it is useful in reducing exposure to allogenic red blood cell transfusion. (Level of Evidence: A) "

"4. We recommend that intraoperative cell salvage is not contraindicated in bowel surgery, provided that initial evacuation of soiled abdominal contents and additional cell washing are performed, and that broad-spectrum antibiotics are used. (Level of Evidence: C) "

Storage Lesions

Class 1

"1. We recommend that RBCs up to 42 days old should be transfused according to the first-in first-out method in, the blood services to minimise wastage of erythrocytes. (Level of Evidence: C) "

Coagulation Management

Class 1

"1. We recommend treatment with fibrinogen concentrate if significant bleeding is accompanied by at least suspected low fibrinogen concentrations or function. (Level of Evidence: C) "

"2. We recommend that a plasma fibrinogen concentration <1.5–2.0 g L-1 or ROTEM/TEG signs of functional fibrinogen deficit should be triggers for fibrinogen substitution. (Level of Evidence: C) "

"3. We recommend that patients on oral anticoagulant therapy should be given prothrombin complex concentrate (PCC) and vitamin K before any other coagulation management steps for severe perioperative bleeding. (Level of Evidence: B) "

Class 2

"1. We suggest an initial fibrinogen concentrate dose of 25–50 mg kg-1. (Level of Evidence: C) "

"2. We suggest that the indication for cryoprecipitate is lack of available fibrinogen concentrate for the treatment of bleeding and hypofibrinogenemia. (Level of Evidence: C) "

"3. In cases of ongoing or diffuse bleeding and low clot strength despite adequate fibrinogen concentrations, it is likely that FXIII activity is critically reduced. In cases of significant FXIII deficiency (i.e. < 60% activity), we suggest that FXIII concentrate (30 IU kg-1) can be administered. (Level of Evidence: C) "

"4. We suggest that PCC (20 –30 IU kg-1) can also be administered to patients not on oral anticoagulant therapy in the presence of an elevated bleeding tendency and prolonged clotting time. Prolonged INR/PT alone is not an indication for PCC, especially in critically ill patients. (Level of Evidence: C) "

"5. We suggest that off-label administration of recombinant activated factor VII (rFVIIa) can be considered for bleeding which cannot be stopped by conventional, surgical or interventional radiological means and/or when comprehensive coagulation therapy fails. (Level of Evidence: C) "

Antifibrinolytics and Tranexamic Acid

Class 1

"1. We recommend the consideration of tranexamic acid (20 –25 mg kg-1). (Level of Evidence: A) "

Class 2

"1. We suggest the use of DDAVP under specific conditions (acquired von Willebrand syndrome). There is no convincing evidence that DDAVP minimises perioperative bleeding or perioperative allogeneic blood transfusion in patients without a congenital bleeding disorder. (Level of Evidence: B) "

Correction of Confounding Factors

Class 1

"1. We recommend maintaining perioperative normothermia because it reduces blood loss and transfusion requirements. (Level of Evidence: B) "

"2. While pH correction alone cannot immediately correct acidosis-induced coagulopathy, we recommend that pH correction should be pursued during treatment of acidotic coagulopathy. (Level of Evidence: C) "

"3. We recommend that rFVIIa should only be considered alongside pH correction. (Level of Evidence: C) "

Class 2

"1. We suggest that rFVIIa may be used in treatment of patients with hypothermic coagulopathy. (Level of Evidence: C) "

"2. We suggest that calcium should be administered during massive transfusion if Ca2+ concentration is low, in order to preserve normocalcaemia (0.9 mmol l-1). (Level of Evidence: B) "

Emergency Radiological/Surgical Interventions to Reduce Blood Loss

Class 2

"1. We suggest that endovascular embolisation is a safe alternative to open surgical intervention after failed endoscopic treatment for upper gastrointestinal bleeding. (Level of Evidence: C) "

"2. We suggest super-selective embolisation as primary therapy for treatment of angiogram positive lower gastrointestinal bleeding. (Level of Evidence: C) "

"3. We suggest embolization as first-line therapy for arterial complications in pancreatitis. (Level of Evidence: C) "

Cost Implications

Class 1

"1. We recommend restricting the use of rFVIIa to its licensed indication because, outside these indications, the effectiveness of rFVIIa to reduce transfusion requirements and mortality remains unproven and the risk of arterial thromboembolic events as well as costs are high. (Level of Evidence: A) "

Algorithms in Specific Clinical Fields

Cardiovascular Surgery

Class 2

"1. We recommend that a prophylactic dose of low molecular weight heparin should be administered subcutaneously 8–12 h before elective CABG surgery. This intervention does not increase the risk of perioperative bleeding. (Level of Evidence: B) "

"2. We recommend that tranexamic acid or EACA should be considered before CABG surgery. (Level of Evidence: A) "

"3. We recommend that intraoperative tranexamic acid or EACA administration should be considered to reduce perioperative bleeding in high-, medium- and low-risk cardiovascular surgery. (Level of Evidence: A) "

"4. We recommend that tranexamic acid should be applied topically to the chest cavity to reduce postoperative blood loss following CABG surgery. (Level of Evidence: C) "

"5. We recommend that fibrinogen concentrate infusion guided by point-of-care viscoelastic coagulation monitoring should be used to reduce perioperative blood loss in complex cardiovascular surgery. (Level of Evidence: B) "

"6. We recommend the use of standardized hemostatic algorithms with predefined intervention triggers. (Level of Evidence: A) "

Class 2

"1.We suggest considering prophylactic preoperative infusion of 2 g fibrinogen concentrate in patients with fibrinogen concentration < 3.8 g/L, because it may reduce bleeding following elective CABG surgery. (Level of Evidence: C) "

"2. We suggest that recombinant FVIIa may be considered for patients with intractable bleeding during cardiovascular surgery once conventional hemostatic options have been exhausted. (Level of Evidence: B) "

"3. We suggest that antiplatelet therapy with aspirin or clopidogrel may be administered in the early postoperative period without increasing the risk of postoperative bleeding. (Level of Evidence: C) "

"4. We suggest that rFVIIa may be considered for patients with intractable bleeding after cardiovascular surgery once conventional haemostatic options have been exhausted. (Level of Evidence: B) "

Gynecological (Non-Pregnant) Bleeding

Class 2

"1. We suggest against normovolemic hemodilution because it does not reduce allogeneic transfusion. (Level of Evidence: A) "

"2. We suggest using preoperative intravenous iron to reduce allogeneic transfusion requirements in gynecological cancer patients receiving chemotherapy. (Level of Evidence: B) "

"3. We suggest using intravenous iron to correct preoperative anemia in women with menorrhagia. (Level of Evidence: B) "

"4. We suggest against the use of tranexamic acid in benign gynecological operations such as myomectomy. (Level of Evidence: B) "

Obstetric Bleeding

Class 1

"1. We recommend that peripartum haemorrhage should be managed by a multidisciplinary team. An escalating management protocol including uterotonic drugs, surgical and/or endovascular interventions, and procoagulant drugs should be available. (Level of Evidence: C) "

"2. We recommend that moderate (<9.5 g dl-1) to sever(<8.5 g dl-1) postpartum anemia be treated with intravenous iron rather than oral therapy. (Level of Evidence: B) "

"3. We recommend the administration of tranexamic acid in obstetric bleeding to reduce blood loss, bleeding duration and the number of units transfused. (Level of Evidence: B) "

"4. We recommend that rFVIIa should only be considered as last line therapy because of its thromboembolic risk. (Level of Evidence: B) "

Class 2

"1. We suggest that patients with known placenta accreta are treated by multidisciplinary care teams. (Level of Evidence: C) "

"2. We suggest that using perioperative cell salvage during caesarean section may decrease postoperative homologous transfusion and reduce hospital stay. (Level of Evidence: B) "

"3. We suggest that treatment with erythropoietin may correct anemia more rapidly than treatment with folic acid and iron. (Level of Evidence: C) "

"4. We suggest assessing fibrinogen concentration in parturients with bleeding, as concentrations <2gl-1 may identify those at risk of severe PPH. (Level of Evidence: C) "

"5. In life-threatening PPH, we suggest a transfusion protocol with a fixed product ratio or individualised procoagulant intervention and factor substitution. (Level of Evidence: C) "

"6. We suggest that tranexamic acid be considered before caesarean section. (Level of Evidence: C) "

"7. In antepartum bleeding, we suggest administration of tranexamic acid. (Level of Evidence: B) "

"8. We suggest that fibrinogen concentration and number of platelets should be optimized before administration of rFVIIa. (Level of Evidence: C) "

Orthopedic Surgery and Neurosurgery

Class 1

"1. In elective orthopedic surgery, we recommend the implementation of a blood transfusion protocol (algorithm), together with staff education. (Level of Evidence: B) "

"2. We recommend that, for orthopedic surgery, monotherapy with aspirin does not need to be discontinued. (Level of Evidence: B) "

"3. We recommend discontinuing dual antiplatelet therapy before urgent intracranial neurosurgery. A risk-benefit analysis is required for the continuation of aspirin monotherapy during neurosurgery. (Level of Evidence: B) "

"4. We recommend against performing orthopaedic surgery during the first three months after bare metal stent implantation or during the first twelve months after drug eluting stent implantation. (Level of Evidence: C) "

"5. Prophylactic use of rFVIIa does not reduce perioperative blood loss or transfusion in non-haemophiliac and non-coagulopathic patients undergoing major orthopedic surgery or neurosurgery, and it may increase the incidence of thromboembolic events. We, therefore, recommend against the prophylactic use of rFVIIa in these clinical settings. (Level of Evidence: B) "

"6. We recommend restricting off-label use of rFVIIa to patients with severe bleeding who are unresponsive to other haemostatic interventions. (Level of Evidence: C) "

"6. In patients with INR >1.5, with life-threatening bleeding or ICH, we recommend that four-factor PCCs (20–40 IU kg-1), supplemented with vitamin K (10 mg by slow intravenous infusion), should be used for rapid reversal of vitamin K-antagonists (VKA). (Level of Evidence: C) "

Class 2

"1. We suggest the use of viscoelastic tests (ROTEM/TEG) for monitoring perioperative haemostasis in major orthopedic surgery and neurosurgery. (Level of Evidence: C) "

"2. We suggest administering tranexamic acid in total hip arthroplasty, total knee arthroplasty, and major spine surgery. (Level of Evidence: A) "

"3. Tranexamic acid may promote a hypercoagulable state for some patients (with pre-existing thromboembolic events, hip fracture surgery, cancer surgery, age over 60 years, women). Therefore, we suggest an individual risk-benefit analysis instead of its routine use in these clinical settings. (Level of Evidence: A) "

"4. We suggest the use of rFVIIa in patients with neutralising antibodies to FVIII undergoing major orthopaedic surgery. (Level of Evidence: C) "

"5. In patients with neutralising antibodies to FVIII undergoing major orthopaedic surgery, we suggest using activated PCCs (e.g. FEIBA, FVIII inhibitor bypassing agents). (Level of Evidence: C) "

"6. New oral anticoagulants, such as rivaroxaban and dabigatran, may increase surgical bleeding and ICH growth. We suggest that PCC, FEIBA or rFVIIa may be used as non-specific antagonists in life threatening bleeding or ICH. (Level of Evidence: C) "

Visceral and Transplant Surgery

Class 1

"1. We recommend against the use of FFP for pre-procedural correction of mild to moderately elevated INR. (Level of Evidence: C) "

"2. We recommend that, in acute liver failure, moderately elevated INR should not be corrected before invasive procedures, with the exception of intracranial pressure monitor insertion. (Level of Evidence: C) "

"3. We recommend the use of perioperative coagulation monitoring using ROTEM/TEG for targeted management of coagulopathy. (Level of Evidence: C) "

"4. We recommend antifibrinolytic drugs for treatment of fibrinolysis (evident from microvascular oozing or TEG/ROTEM clot lysis measurement) and not for routine prophylaxis. Marginal grafts (e.g. donation after cardiac death) increase the risk of fibrinolysis post-reperfusion. (Level of Evidence: C) "

"4. We recommend against rFVIIa for prophylaxis; rFVIIa should be used only as rescue therapy for uncontrolled bleeding. (Level of Evidence: C) "

Class 2

"1. We suggest a platelet count of 50 000 ml-1 as a threshold for platelet transfusion before liver biopsy. (Level of Evidence: C) "

"2. We suggest that antifibrinolytic drugs should be considered in cirrhotic patients undergoing liver resection. (Level of Evidence: B) "

Acute Upper Gastrointestinal Bleeding

Class 1

"1. We recommend that acute variceal bleeding should be managed by a multidisciplinary team. A specific multimodal protocol for upper gastrointestinal hemorrhage should be available. (Level of Evidence: C)"

"2. We recommend that early treatment involves immediate use of vasopressors (somatostatin or terlipressin) to reduce bleeding and early interventional endoscopy. Antibiotics must be started on admission. (Level of Evidence: A)"

"3. rFVIIa should be used only as rescue therapy; we recommend against its routine use. (Level of Evidence: C)"

Coagulopathy and Renal Disease

Class 2

"1. We suggest that conjugated estrogen therapy should be used in uremia. (Level of Evidence: C)"

"2. We suggest that desmopressin should be considered for reducing bleeding during surgery and for managing acute bleeding in uremic patients. (Level of Evidence: C)"

Pediatric Surgery

Class 1

"1. We recommend against the use of rFVIIa in children. (Level of Evidence: C)"

Class 2

"1. We suggest the use of perioperative coagulation analysis using viscoelastic point-of-care monitoring (ROTEM/TEG) for timely detection of coagulation defects including dilutional coagulopathy and hyperfibrinolysis. (Level of Evidence: C)"

"2. We suggest that a critical hemoglobin threshold of 8 g/dl for RBC transfusion may be safe in severe pediatric perioperative bleeding. (Level of Evidence: C)"

"3. We suggest that transfusion of platelet concentrates may be considered if platelet count is <50,000–100,000/µl. (Level of Evidence: C)"

"4. We suggest that fibrinogen concentrate (30–50 mg/kg) or cryoprecipitate (5 ml/kg) may be used to increase plasma fibrinogen concentrations above trigger values of 1.5–2.0 g/l or FIBTEM MCF > 7 mm in bleeding children. (Level of Evidence: C)"

"5. We suggest that FFP may be used if no other fibrinogen source is available. (Level of Evidence: C)"

"6. We suggest against the routine use of desmopressin in the absence of hemophilia A or mild von Willebrand disease. (Level of Evidence: C)"

"7. We suggest that perioperative antifibrinolytic therapy should be used to reduce blood loss and transfusion requirements in cardiac and non-cardiac pediatric surgery. (Level of Evidence: A)"

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

von Willebrand Disease

Class 1

"1. We recommend the use of bleeding assessment tools for predicting the perioperative risk of bleeding. (Level of Evidence: C)"

"2. We recommend that patients with VWD be managed perioperatively in collaboration with a hematologist. (Level of Evidence: C)"

"3. We recommend desmopressin as a first-line treatment for minor bleeding/surgery in patients with VWD, after a trial testing. The regimen is specified by published guidelines. (Level of Evidence: C)"

"4. We recommend replacement of VWF with plasma-derived products for major bleeding/surgery. Treatment regimens are specified by published guidelines. (Level of Evidence: C)"

Class 2

"1. We suggest that if VWD is suspected preoperatively, the patient be referred to a hematologist for assessment and planning of the intervention. (Level of Evidence: C)"

"2. We suggest that antifibrinolytic drugs be used as hemostatic adjuncts. Treatment regimens are specified by published guidelines. (Level of Evidence: C)"

"3. We suggest that platelet transfusion may be used only in case of failure of other treatments. (Level of Evidence: C)"

Platelet Defects

Class 1

"1. We recommend the use of a bleeding assessment tool for predicting the perioperative risk of bleeding. (Level of Evidence: C)"

"2. We recommend that patients with severe inherited platelet disorders should be managed perioperatively in collaboration with a hematologist. (Level of Evidence: C)"

"3. We recommend that rFVIIa treatment should be considered in patients with Glanzmann thrombasthenia undergoing surgery. (Level of Evidence: C)"

"4. We recommend against routine platelet transfusion in patients with inherited platelet disorders. (Level of Evidence: C)"

Class 2

"1. We suggest referring the patient to a hematologist for assessment and planning of the intervention if inherited platelet defects are suspected preoperatively. (Level of Evidence: C)"

"2. We suggest preoperative hemostatic correction in patients with inherited platelet disorders. (Level of Evidence: C)"

"3. We suggest desmopressin be used to prevent/control perioperative bleeding in patients with inherited platelet defects. (Level of Evidence: C)"

"4. We suggest antifibrinolytic drugs be used as hemostatic adjuncts in procedures involving patients with inherited platelet defects. (Level of Evidence: C)"

Hemophilia A and B

Class 1

"1. We recommend that hemophilia patients should be referred preoperatively to a hematologist for assessment/intervention. (Level of Evidence: C)"

"2. We recommend that surgery in hemophilia patients should be performed in specialised centres with expertise in coagulation disorders. (Level of Evidence: C)"

"3. We recommend adequate perioperative replacement therapy to ensure safe surgery in hemophilia patients. (Level of Evidence: C)"

"4. We recommend either recombinant products or plasma-derived concentrates for perioperative replacement therapy in hemophilia patients. (Level of Evidence: C)"

Class 2

"1. We suggest that perioperative replacement therapy (target factor level and duration) in hemophilia patients follows published guidelines. (Level of Evidence: C)"

"2. We suggest that coagulation factors be given perioperatively by continuous infusion. (Level of Evidence: C)"

"3. We suggest either rFVIIa or activated PCCs for hemophilia patients with inhibitors. (Level of Evidence: C)"

"4. We suggest antifibrinolytic drugs as perioperative adjunct therapy in hemophilia patients. (Level of Evidence: C)"

"5. We suggest individualized perioperative thromboprophylaxis in hemophilia patients. (Level of Evidence: C)"

Rare Bleeding Disorders

Class 1

"1. We recommend that patients with rare bleeding disorders should be referred preoperatively to a hematologist for assessment/intervention. (Level of Evidence: C)"

"2. We recommend that surgery in patients with rare bleeding disorders should be carried out in consultation with a hematologist with experience in factor deficiencies. (Level of Evidence: C)"

Class 2

"1. We suggest that rFVIIa be used in perioperative bleeding due to inherited FVII deficiency. (Level of Evidence: C)"

"2. If rFVIIa is given to control perioperative bleeding in inherited FVII deficiency, we suggest lower doses than in hemophilia patients. (Level of Evidence: C)"

Sources

• 2013 ESA Guidelines for the Management of Severe Perioperative Bleeding