Antikoagulation und perioperatives “bridging“

Before performing proctological surgery on patients receiving long-term anticoagulation therapy, the risk of bleeding and thromboembolism have to be considered. Based on these risks the treatment with vitamin K antagonists should either be continued or switched to low molecular weight heparin for the time around the surgery (bridging). Patients receiving direct oral anticoagulants do not need a bridging due to the short half-life and the rapid resumption of pharmaceutical effects but need to stop taking the medication perioperatively. Those patients treated with antiplatelet drugs as monotherapy should continue taking them perioperatively if deemed medically necessary. In the case of dual antiplatelet treatment after stent implantation, elective surgery should be postponed until the patient can be treated with antiplatelet monotherapy.     

Antikoagulation und perioperatives Bridging

Perioperative management of anticoagulant-treated patients undergoing a surgical or invasive procedure is a challenge for treating physicians. On one hand, bleeding complications caused by the intervention must be avoided; on the other hand, after discontinuation of anticoagulants the risk of severe thromboembolic complications, such as myocardial infarction, stroke, or pulmonary embolism, is increased. For optimal bridging therapy and prior to surgery, all participating physicians must collaborate to estimate the risks of bleeding and thromboembolism.The risk of thromboembolism is determined by both the underlying disease that led to anticoagulation therapy and also by the surgery itself. The risk of bleeding is influenced by the type and extent of surgery, as well as by individual patient characteristics. Localization and compressibility of bleeding must be considered. Finally, the risks of bleeding and thromboembolism should be classified as low, medium, or high; and then evaluated in comparison with each other.During perioperative interruption of vitamin K antagonist treatment, unfractionated or low molecular weight heparin can be used for bridging. Owing to their short duration of action, new oral anticoagulants do not require preoperative bridging with heparin.When planning a surgical intervention in patients with one or two antiplatelet drugs, the risk of thromboembolism has to be compared to the risk of bleeding. The risk of thromboembolism depends crucially on whether the coronary heart disease (CHD) is stable or unstable; whether a stent has recently been implanted; and, if so, whether this is coated or uncoated. Depending on the risk of bleeding and the urgency of surgery, it must be assessed whether the overall risk can be reduced by delaying surgery. In principle and wherever possible in patients with known CHD, one antiplatelet drug should be maintained perioperatively.     

When to stop,how to reverse,and when to restart antithrombotic drugs periendoscopically in nonvariceal upper gastrointestinal bleeding

Upper gastrointestinal (GI) (UGI) bleeding in patients taking antithrombotics including antiplatelet agents, vitamin K antagonists, and direct oral anticoagulants is challenging because of varying clinical presentations that include the severity of hemorrhage, the type and magnitude of anticoagulation, the patient׳s underlying thromboembolic risk, and the specific bleeding lesion with attendant ability to achieve successful endoscopic hemostasis. Interruption of antithrombotics for bleeding management exposes the patient to the underlying risk of thromboembolic events from the underlying cardiovascular state, whereas continuation or restarting antithrombotics subjects the patient to ongoing or recurrent bleeding. The balance between excessive bleeding vs thrombosis is the principle for deciding optimal management of these patients.This article focuses on the management of antithrombotic-associated nonvariceal UGI bleeding describing the approach to managing these patients from the gastroenterologist׳s perspective. The focus will include risk assessment for patients taking antithrombotics, determination of residual antithrombotic effect to guide selection and timing of reversal agents, and strategies for restarting antithrombotics once hemostasis has been achieved.     

Prevention of gastrointestinal events in patients on antithrombotic therapy in the peri‐endoscopy period: Review of new evidence and recommendations from recent guidelines

Management of patients on antithrombotic therapy undergoing endoscopic procedures can be challenging. Although guidelines from major gastrointestinal endoscopy societies provide useful recommendations in this regard, data are limited concerning the bleeding risk of new complex endoscopic procedures and the management of novel anticoagulants in patients needing invasive procedures. The approach to the management of antithrombotic therapy often needs to be formulated on an individual basis, especially in patients with high thrombotic risk undergoing a high‐risk endoscopic procedure. In addition to the procedure‐related bleeding risk, endoscopists also need to consider the urgency of the endoscopic procedure, the thromboembolic risk of the patient if antithrombotic therapy is temporarily withheld, and the timing of discontinuation/resumption of antithrombotic therapy in the decision‐making process. Diagnostic endoscopic procedures with or without biopsy can often be done without interruption of antithrombotic therapy. If possible, elective procedures with high bleeding risk should be delayed in patients on antithrombotic therapy for conditions with high thrombotic risk. If high‐risk procedures cannot be delayed in these patients, thienopyridines, traditional and novel anticoagulants are usually withheld, whereas aspirin withdrawal is decided on a case by case basis. In patients with high thrombotic risk, communication with the prescribing clinician before proceeding to procedures with high bleeding risk is particularly important in optimizing the peri‐procedural management plan of antithrombotic therapy.     

Management of antiplatelet or anticoagulant therapy in endoscopy:A review of literature

Endoscopic procedures hold a basal risk of bleeding that depends on the type of procedure and patients’ comorbidities. Moreover, they are often performed in patients taking antiplatelet and anticoagulants agents, increasing the potential risk of intraprocedural and delayed bleeding. Even if the interruption of antithrombotic therapies is undoubtful effective in reducing the risk of bleeding,the thromboembolic risk that follows their suspension should not be underestimated. Therefore, it is fundamental for each endoscopist to be aware of the bleeding risk for every procedure, in order to measure the risk-benefit ratio for each patient. Moreover, knowledge of the proper management of antithrombotic agents before endoscopy, as well as the adequate timing for their resumption is essential.This review aims to analyze current evidence from literature assessing, for each procedure, the basal risk of bleeding and the risk of bleeding in patients taking antithrombotic therapy, as well as to review the recommendation of American society for gastrointestinal endoscopy, European society of gastrointestinal endoscopy, British society of gastroenterology, Asian pacific association of gastroenterology and Asian pacific society for digestive endoscopy guidelines for the management of antithrombotic agents in urgent and elective endoscopic procedures.     

Endoscopic procedures for patients on antithrombotic medication--risks and methods

The decision how to handle an antithrombotic treatment when an intervention during GI endoscopy is planned is influenced both by the risk of bleeding and by the thromboembolic risk when treatment is suspended. The risk of bleeding is negligible even when on oral anticoagulants in diagnostic procedures with standard forceps biopsies. Oral anticoagulation has to be stopped, however, when planning invasive procedures such as polypectomy or EPT. In the case of patients with a high risk of thromboembolic complications such as artificial valves in mitral position or atrial fibrillation with risk factors, one has to temporarily switch to anticoagulants with shorter action ("bridging"). Treatment with inhibitors of platelet function does not preclude procedures with a low risk of bleeding including forceps biopsy. Urgent procedures with a high risk of bleeding should be performed after stopping clopidogrel one week previously but only after consultation with the treating cardiologist. In the case of colonoscopy, in particular as a screening procedure, there are two options: 1) stopping oral anticoagulation (with or without bridging) or clopidogrel, respectively, or 2) continuing antithrombotic treatment and performing a second elective endoscopy for polypectomy with tapered antithrombotic medication if polyps are found which are not amenable to resection by biopsy forceps. The choice between these two options has to be made individually.     

Bridging of oral anticoagulation therapy for invasive procedures

The management of patients who need temporary interruption of chronic oral anticoagulant (OAC) therapy for an elective surgical or invasive procedure is problematic and complex. Patient and procedural risk factors for thrombosis and bleeding, anticoagulant-related risks of bleeding, and clinical consequences of a thrombotic or bleeding event need to be assessed and properly risk-stratified in the perioperative period. Certain procedures, such as dental, endoscopic, and cutaneous procedures, can be completed without discontinuing OAC, but most procedures with a high bleeding risk (including major surgeries) will necessitate temporary discontinuation of OAC. Bridging therapy with shorter-acting anticoagulants, such as heparin, for patients at intermediate to high risk of thromboembolism represents one strategy to maintain functional anticoagulation during this period. Large, prospective cohort studies and registries of patients on chronic OAC who underwent bridging therapy mostly with low-molecular-weight heparin have been completed recently. This paper reviews these clinical data on bridging therapy and provides an evidence-based perioperative management strategy for the at-risk patient on chronic OAC.     

The debate concerning oral anticoagulation: whether to suspend oral anticoagulants during dental treatment

The management of patients taking long-term oral anticoagulants who require dental surgery is still highly controversial. The risk of bleeding associated with dental treatment under oral anticoagulants must be weighed against the risk of thromboembolism associated with suspension of antithrombotic therapy. Mortality and morbidity associated with thromboembolic events are higher than those associated with hemorrhagic events after minor oral surgery procedures. Evidence-based information does not support oral anticoagulant suspension before minor oral surgery. The authors propose a management protocol for chronically anticoagulated patients who require a dental procedure, to reduce both thromboembolic risk and the risk of bleeding.     

Antithrombotic therapy in TAVI

Transcatheter aortic valve implantation (TAVI) carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning optimal antithrombotic therapy after TAVI are still under debate. In the present review, we aimed to identify all relevant studies evaluating antithrombotic therapeutic strategies in relation to clinical outcomes after the procedure. Four randomized control trials (RCT) were identified analyzing the post-TAVI antithrombotic strategy with all of them utilizing aspirin lifelong plus clopidogrel for 3?6 months. Seventeen registries have been identified, with a wide variance among them regarding baseline characteristics, while concerning antiplatelet therapy, clopidogrel duration was ranging from 3?12 months. Four non-randomized trials were identified, comparing single vs. dual antiplatelet therapy after TAVI, in respect of investigating thromboembolic outcome events over bleeding complications. Finally, limited data from a single RCT and a retrospective study exist with regards to anticoagulant treatment during the procedure and the optimal antithrombotic therapy when concomitant atrial fibrillation. In conclusion, due to the high risk and frailty of the treated population, antithrombotic therapy after TAVI should be carefully evaluated. Diminishing ischaemic and bleeding complications remains the main challenge in these patients with further studies to be needed in this field.     

Postoperative bleeding in patients on antithrombotic therapy after gastric endoscopic submucosal dissection

AIM To investigated the relationship between postoperative bleeding following gastric endoscopic submucosal dissection(ESD) and individual antithrombotic agents.METHODS A total of 2488 gastric neoplasms in 2148 consecutive patients treated between May 2001 and June 2016 were studied. The antithrombotic agents were categorized into antiplatelet agents, anticoagulants, and other antithrombotic agents, and we included combination therapies [e.g., dual antiplatelet therapy(DAPT)]. The risk factors associated with post-ESD bleeding, namely, antithrombotic agents overall, individual antithrombotic agents, withdrawal or continuation of antithrombotic agents, and bleeding onset period(during the first six days or thereafter), were analyzed using univariate and multivariate analyses.RESULTS The en bloc resection and complete curative resection rates were 99.2% and 91.9%, respectively. Postoperative bleeding occurred in 5.1% cases. Bleeding occurred in 10.3% of the patients administered antithrombotic agents. Being male(P = 0.007), specimen size(P 0.001), and antithrombotic agent used(P 0.001) were independent risk factors for postoperative bleeding. Heparin bridging therapy(HBT)(P = 0.002) and DAPT/multidrug combinations(P 0.001) were independent risk factors associated with postoperative bleeding. The bleeding rate of the antithrombotic agent continuation group was significantly higher than that of the withdrawal group(P 0.01). Bleeding within postoperative day(POD) 6 was significantly higher in warfarin(P = 0.015), and bleeding after POD 7 was significantly higher in DAPT/multidrug combinations(P = 0.007). No thromboembolic events were reported.CONCLUSION We must closely monitor patients administered HBT and DAPT/multidrug combinations after gastric ESD, particularly those administered multidrug combinations after discharge.     

Anithrombotische Therapie und Vorhofflimmern

Current guidelines recommend dual antiplatelet therapy preferably with prasugrel or ticagrelor for 12 months in patients after acute coronary syndrome with stent implantation. Problems occur in patients with a need for oral anticoagulation, such as patients with atrial fibrillation. In these patients a combination of oral anticoagulation and platelet inhibitors is necessary. Antithrombotic combination therapy is known to increase bleeding complications. In a small randomized trial the combination of a vitamin K antagonist (VKA) and clopidogrel decreased bleeding compared to triple therapy with VKA, clopidogrel and aspirin. The new oral anticoagulants have consistently been shown to decrease bleeding complications compared to VKAs regardless of additional antiplatelet therapy. Because of the lack of randomized trials the individual decision about the intensity and duration of antithrombotic combination therapy should be based on the bleeding and ischemic risk in the individual patient. However, in most patients in addition to oral anticoagulation, antiplatelet monotherapy preferably with clopidogrel seems necessary only for 3–6 months.     

Periprocedural Bridging in Patients with Venous Thromboembolism: A Systematic Review

BackgroundVitamin K antagonists (VKA) are the most widely used anticoagulants, and bridging is commonly administered during periprocedural VKA interruption. Given the unclear benefits and risks of periprocedural bridging in patients with previous venous thromboembolism, we aimed to assess recurrent venous thromboembolism and bleeding outcomes with and without bridging in this population.MethodsWe performed a systematic review searching the PubMed and Embase databases from inception to December 7, 2017 for randomized and nonrandomized studies that included adults with previous venous thromboembolism requiring VKA interruption to undergo an elective procedure, and that reported venous thromboembolism or bleeding outcomes. Quality of evidence was graded by consensus.ResultsWe included 28 cohort studies (20 being single-arm cohorts) with, overall, 6915 procedures for analysis. In 27 studies reporting perioperative venous thromboembolism outcomes, the pooled incidence of recurrent venous thromboembolism with bridging was 0.7% (95% confidence interval [CI], 0.4%-1.2%) and 0.5% (95% CI, 0.3%-0.8%) without bridging. Eighteen studies reported major or nonmajor bleeding outcomes. The pooled incidence of any bleeding was 3.9% (95% CI, 2.0%-7.4%) with bridging and 0.4% (95% CI, 0.1%-1.7%) without bridging. In bridged patients at high thromboembolic risk, the pooled incidence for venous thromboembolism was 0.8% (95% CI, 0.3%-2.5%) and 7.5% (95% CI, 3.1%-17.4%) for any bleeding. Quality of available evidence was very low, primarily due to a high risk of bias of included studies.ConclusionsPeriprocedural bridging increases the risk of bleeding compared with VKA interruption without bridging, without a significant difference in periprocedural venous thromboembolism rates.     

Periprocedural reversal and bridging of anticoagulant treatment

Anticoagulants are effective agents in reducing the risk of thromboembolism but the most important adverse effect of these agents is the occurrence of bleeding. Bleeding complications may occur spontaneously but the risk of bleeding is particularly increased in case of trauma or around invasive procedures. If patients being treated with anticoagulants need to undergo an invasive intervention, physicians need to consider whether to interrupt the use of this medication or to allow its use to be continued. Suspending the use of anticoagulants increases the risk of thrombosis, whereas continued use may cause bleeding complications. To shorten the period in which anticoagulant treatment is interrupted, bridging strategies have been advocated. No evidence-based scientific research has been carried out regarding best practice for the perioperative use of anticoagulants. The periprocedural anticoagulation policy in patients should be individualised based on the risk of a thromboembolic complication (which can be estimated with available scoring systems) offset against the bleeding risk associated with the intervention.     

Thromboembolieprophylaxe bei Vorhofflimmern

Morbidity and mortality associated with atrial fibrillation are mainly related to thromboembolic complications, particularly ischemic strokes. The prevention of thromboembolism is an important component in the management of patients with atrial fibrillation. The choice of optimum antithrombotic therapy for a given patient depends on the risk of thromboembolism, on the one hand, and the risk of intracerebral hemorrhage, on the other hand. Concerning the benefit-to-risk stratification the problem lies in the similar and sometimes even identical risk factors for both thromboembolism and haemorrhage. At present, oral vitamin K antagonists are recommended for patients with atrial fibrillation at moderate or high risk of ischemic stroke. The thromboembolic risk should be assessed using validated stratification schemes, such as the CHADS₂ score. Aspirin alone is recommended for patients at low risk of thromboembolic complications. A combination of anticoagulant and antiplatelet drugs is necessary in patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation, but the optimal therapeutic management of these patients has not yet been defined. Hopefully, the development of new antithrombotic agents being easier to use and having a superior benefit-to-risk ratio will extend effective prevention of thromboembolic events to a greater part of the atrial fibrillation population at risk.     

Antithrombotic treatment in anticoagulated atrial fibrillation patients undergoing percutaneous coronary intervention

Coronary artery disease coexists in a clinically relevant number of patients with atrial fibrillation and it often requires percutaneous coronary intervention. These patients represent a particular challenge for clinicians in terms of antithrombotic management. They require combined antiplatelet–anticoagulant therapy to reduce the risk of recurrent ischemic cardiac events and stroke; however, this antithrombotic strategy is associated with an increased risk of bleeding complications. In the absence of randomized, controlled clinical trials, the majority of current recommendations rely on the results of cohort studies, meta-analyses, post-hoc analyses and subgroup analyses of large, phase III studies. Based on the available evidence, the present review discusses the optimal antithrombotic strategy for patients receiving chronic anticoagulant therapy due to atrial fibrillation who require antiplatelet treatment after acute coronary syndrome and/or percutaneous coronary intervention, and discusses the issue of dental procedures. The correct planning of therapy significantly reduces the risk of bleeding complications and thromboembolic events.Key messagesIn order to reduce the occurrence of recurrent cardiac ischemic events and stroke, anticoagulated patients with acute coronary syndrome and/or percutaneous coronary intervention require a combination of therapies including anticoagulants and antiplatelet drugs.Using the newest optimal combination of therapeutic strategies reduces the risk of haemorrhagic complications.     

Bridging antiplatelet therapy in patients requiring cardiac and non-cardiac surgery: from bench to bedside

Dual antiplatelet therapy (DAPT) is the mainstay of pharmacotherapy after an acute coronary syndrome or percutaneous coronary intervention. While patients requiring interruption of DAPT at the time of cardiac or noncardiac surgery face an increased risk of thrombotic complications, the opportunity of continuing DAPT in the perioperative period should be balanced against the risk of bleeding. Tailoring antiplatelet therapy on patient- and surgery-specific characteristics mandates a clear understanding of pharmacodynamic and clinical data on using antithrombotic agents in the perioperative period. This is also important given the introduction of novel antiplatelet agents that are already adopted in practice (prasugrel, ticagrelor) or will likely be adopted in the near future (cangrelor). This article explores the theoretical background and rationale for bridging patients on antiplatelet drugs to their surgical procedure, and provides insights on how patient and procedural characteristics translate into different considerations for the use of antithrombotic agents in the surgical setting.     

Management of Anticoagulants and Antiplatelet Agents During Colonoscopy

Colonoscopy frequently is performed for patients who are taking aspirin, nonsteroidal anti-inflammatory drugs, antiplatelet agents, and other anticoagulants. These colonoscopies often involve polypectomy, which can be complicated by bleeding. The risks of precipitating thromboembolic complications if anticoagulants are stopped must be weighed against the risk of postpolypectomy bleeding if these agents are continued. This article systematically reviews the management of anticoagulation during elective and emergency colonoscopy. For patients undergoing colonoscopic polypectomy, the overall risk of postpolypectomy bleeding is <0.5%. Risk factors for postpolypectomy bleeding include large polyp size and anticoagulant use, especially warfarin and thienopyridines. For patients who do not stop aspirin or other nonsteroidal anti-inflammatory drugs prior to colonoscopy, the rate of postpolypectomy bleeding is not significantly different from that for patients who do not take those medications. For patients who continue thienopyridines and undergo polypectomy, the risk of delayed postpolypectomy bleeding is approximately 2.4%. Even for patients who interrupt warfarin, the risk of postpolypectomy bleeding is increased. The direct oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) have a rapid onset and offset of action, and periprocedural bridging generally is not necessary. For the thienopyridines, warfarin, and the direct oral anticoagulants, the decision to interrupt or continue these agents for endoscopy will involve considerable exercise of clinical judgment.     

Coronary stent implantation in patients committed to long-term oral anticoagulation therapy: successfully navigating the treatment options

Current guidelines and recommendations on the antithrombotic management of patients committed to long-term oral anticoagulation (OAC) therapy undergoing coronary stent implantation are recognized to be flawed by numerous limitations. Nevertheless, triple therapy (TT) (warfarin, aspirin, and clopidogrel) is regarded as the most effective regimen for preventing major adverse cardiac events, stent thrombosis, and stroke, albeit at the price of an increased risk of bleeding. Recent insights into the efficacy and safety of TT derived from larger, prospective studies have expanded current knowledge by showing that TT is likely associated with minor, rather than major bleeding, and that accurate stratification of thromboembolic and hemorrhagic risk may enable optimization of the antithrombotic strategy at discharge. Therefore, TT should be prescribed to patients at moderate to high thromboembolic risk, owing to a favorable net clinical benefit. Discontinuation of OAC and substitution with dual antiplatelet therapy is the optimal strategy for patients at low thromboembolic risk.     

Dilated Cardiomyopathy and Role of Antithrombotic Therapy

BackgroundThere is no consensus as to whether anticoagulation has a favorable risk:benefit in reducing thromboembolic events in patients with heart failure (HF) secondary to dilated cardiomyopathy who do not suffer from atrial fibrillation or primary valvular disease.Methods and ResultsThe literature reviewed on this topic included most recent and ongoing studies that assessed the use of anticoagulation for this population. Several large retrospective studies showed an increased risk of thromboembolic events among patients with depressed left ventricular function. The relative risk of stroke in individuals with HF from all causes was found to be 4.1 for men and 2.8 for women, but confounding comorbidities (such as atrial fibrillation and coronary artery disease) were commonly present. Currently, there are no randomized prospective trials to guide the use of antithrombotics for these patients, and the risk of bleeding secondary to anticoagulation has limited the use of oral anticoagulants for prevention of thrombosis. Among patients with HF, increasing age directly correlates with both major bleeding and thromboembolic events, with a 46% relative risk of bleeding for each 10-year increase in age older than 40 years.ConclusionsTo date, there is no agreement on appropriate antithrombotic treatment (if any) for primary thromboembolism prophylaxis in patients with dilated cardiomyopathy with sinus rhythm. In recent years, several promising prospective trials were terminated prematurely due to inadequate enrollment. The Warfarin Aspirin-Reduced Cardiac Ejection Fraction trial may provide evidence regarding the use of anticoagulation for patients with decreased myocardial function.     

Clinical problems with antithrombotic therapy for endoscopic submucosal dissection for gastric neoplasms

Endoscopic submucosal dissection(ESD) is minimally invasive and thus has become a widely accepted treatment for gastric neoplasms,particularly for patients with comorbidities.Antithrombotic agents are used to prevent thrombotic events in patients with comorbidities such as cardio-cerebrovascular diseases and atrial fibrillation.With appropriate cessation,antithrombotic therapy does not increase delayed bleeding in low thrombosis-risk patients.However,high thrombosisrisk patients are often treated with combination therapy with antithrombotic agents and occasionally require the continuation of antithrombotic agents or heparin bridge therapy(HBT) in the perioperative period.Dual antiplatelet therapy(DAPT),a representative combination therapy,is frequently used after placement of drug-eluting stents and has a high risk of delayed bleeding.In patients receiving DAPT,gastric ESD may be postponed until DAPT is no longer required.HBT is often required for patients treated with anticoagulants and has an extremely high bleeding risk.The continuous use of warfarin or direct oral anticoagulants may be possible alternatives.Here,we show that some antithrombotic therapies in high thrombosis-risk patients increase delayed bleeding after gastric ESD,whereas most antithrombotic therapies do not.The management of high thrombosis-risk patients is crucial for improved outcomes.