Unterbrechung antithrombotischer Behandlung (Bridging) bei kardialen Erkrankungen

In patients who need antithrombotic therapy for cardiovascular diseases (anticoagulants or antiplatelet therapy) perioperative consideration of the bridging strategy is mandatory. The risks of thromboembolism and bleeding have to be taken into account. Periprocedural management depends on the urgency of the procedure. In emergency cases the operation has to be done in spite of antithrombotic therapy. In patients who need antithrombotics only for a limited period of time, an elective procedure could be performed after the time of anticoagulation or dual antiplatelet therapy. If heart valve replacement or coronary stenting is performed in a patient with known future need of an elective procedure, devices should be preferred for implantation which need antithrombotics only for a short time post implantation. In all other cases the risk of bleeding and the risk of thromboembolism should be balanced: In patients at low risk for a thromboembolic event, cessation of effective antithrombotic therapy is reasonable. However, patients with intermediate to high risk for thromboembolic events need specific bridging treatment depending on the risk of bleeding. Continuation of antithrombotics often increases just the risk of mild to intermediate bleeding, but it prevents occurrence of life-threatening thromboembolic events. For optimal periprocedural treatment of patients on anticoagulants or antiplatelet therapy cooperation of the medical disciplines involved is mandatory.     

Anticoagulant therapy, anti-platelet agents and gastrointestinal endoscopy

BACKGROUND: The increasing use of anticoagulant therapy and anti-platelet agents in the primary and secondary prevention of cardiovascular, cerebrovascular and venous thromboembolic disease has increased the need for guidelines for managing these agents prior to gastrointestinal endoscopy, particularly if therapeutic manoeuvres are required. The continuation of anticoagulant therapy increases the risk of haemorrhagic complications of gastrointestinal endoscopy. Temporary suspension of anticoagulant therapy exposes the patient to the risk of thromboembolism associated with the underlying condition requiring anticoagulant treatment. CONCLUSIONS: This article reviews the literature and proposes guidelines for the management of patients taking anticoagulant and anti-platelet agents who require gastrointestinal endoscopy.     

Endoscopic treatment of ulcer bleeding

Opinion statement Upper gastrointestinal (UGI) bleeding secondary to ulcer disease occurs commonly and results in significant patient morbidity and medical expense. After initial resuscitation, carefully performed endoscopy provides an accurate diagnosis of the source of the UGI hemorrhage and can reliably identify those high-risk subgroups that may benefit most from endoscopic hemostasis. Large-channel therapeutic endoscopes are recommended. Endoscopists should be very experienced in management of patients with UGI hemorrhage, including the use of various hemostatic devices. For patients with major stigmata of ulcer hemorrhage—active arterial bleeding, nonbleeding visible vessel, and adherent clot—combination therapy with epinephrine injection and either thermal coaptive coagulation (with multipolar or heater probe) or endoclips is recommended. High-dose intravenous proton-pump inhibitors are recommended as concomitant therapy with endoscopic hemostasis of major stigmata. Patients with minor stigmata or clean-based ulcers will not benefit from endoscopic therapy and should be triaged to less intensive care and be considered for early discharge. Effective endoscopic hemostasis of ulcer bleeding can significantly improve outcomes by reducing rebleeding, transfusion requirement, and need for surgery, as well as reduce cost of medical care.     

Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices

Axial-flow LVADs have become an integral tool in the management of end-stage heart failure. Consequently, nonsurgical bleeding has emerged as a major source of morbidity and mortality in this fragile population. The mechanisms responsible for these adverse events include acquired von Willebrand disease, GI tract angiodysplasia formation, impaired platelet aggregation, and overuse of anticoagulation therapy. Because of ongoing concerns for pump thrombosis and thromboembolic events, the thrombotic/bleeding paradigm has led to a difficult clinical dilemma for those managing patients treated with axial flow LVADs. As the field progresses, advances in the understanding of the pathological mechanisms underlying bleeding/thrombosis risk, careful risk stratification, and potential use of novel anticoagulants will all play a role in the management of the LVAD patient.     

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.     

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.     

Risk stratification and definitive hemostasis of nonvariceal upper gastrointestinal bleeding with blood flow detection and combination techniques

Nonvariceal upper gastrointestinal (UGI) hemorrhage remains a significant health and economic burden. As the use of urgent endoscopy for UGI hemorrhage has increased, there has been a decline in associated mortality. Endoscopic hemostasis is based on risk stratification of stigmata of recent hemorrhage. A Doppler endoscopic probe can provide further risk stratification by detecting arterial blood flow under the lesion and as a guide to successful endoscopic treatment. Standard treatment options for endoscopic hemostasis include submucosal injection therapy usually in combination with either thermal coagulation or through-the-scope clips. A large over-the-scope clip, which has been used to close fistulas and perforations, has been shown to be effective in cases of refractory nonvariceal UGI hemorrhage, and might also be useful in other types of gastrointestinal bleeding.     

Restarting anticoagulation in prosthetic heart valve patients after intracranial haemorrhage: a 2-year follow-up

35 patients with oral anticoagulant (OAC) related intracranial or intraspinal haemorrhage were studied to determine treatment received, outcome and rate of recurrent bleeding and thromboembolism after restarting OAC. All patients underwent active anticoagulant reversal and in 14 patients with prosthetic heart valves (PHV) the INR remained below 2.0 for 0–19 d (median 7) with no thromboembolic events. 10 patients received heparin, although a therapeutic level was rarely achieved. 13 patients with PHV were restarted on OAC and followed for a median 23.5 months. One patient had recurrent intracranial bleeding. 3/13 patients had cerebral embolic events despite anticoagulation. We conclude that in PHV patients temporary cessation of OAC is safe and the risk of recurrent bleeding after restarting OAC is low.     

Upper gastrointestinal haemorrhage complicating antiplatelet treatment with aspirin and/or clopidogrel: where we are now?

A large number of patients require antiplatelet therapy (mainly aspirin and/or clopidogrel). Recent studies suggest that the combination of these agents is useful in patients with acute coronary syndrome and after percutaneous coronary intervention with stent placement. On the other hand, bleeding complications, most of which arise from the upper gastrointestinal (UGI) tract, can limit the use of antiplatelet drugs. Clopidogrel appears to be associated with fewer UGI side effects and bleeding compared with aspirin. However, a history of previous UGI bleeding is a major risk factor for clopidogrel-associated bleeding. The use of proton-pump inhibitors (PPIs) decreases the rate of UGI bleeding in patients receiving aspirin or clopidogrel. Furthermore, a recent study suggested that the administration of low-dose aspirin plus high-dose esomeprazole (a potent PPI) was associated with fewer episodes of UGI bleeding than clopidogrel alone in patients with a history of recent UGI haemorrhage. However, this study had several limitations and its results should be cautiously extrapolated into clinical practice. The combination of aspirin plus clopidogrel increases the risk of UGI bleeding. Unfortunately, there are no data on the effect of PPI prophylaxis in this setting. Available evidence suggests that where aspirin and/or clopidogrel are to be started or continued in patients with a recent history of UGI ulceration or bleeding (after ulcer healing and eradication of H. pylori infection), treatment with a PPI is a useful precaution. The patients should also be carefully monitored for recurrence of UGI bleeding.     

Dental Surgery and Antiplatelet Agents: Bleed or Die

In patients taking antiplatelet medications who are undergoing dental surgery, physicians and dentists must weigh the bleeding risks in continuing antiplatelet medications versus the thrombotic risks in interrupting antiplatelet medications. Bleeding complications requiring more than local measures for hemostasis are rare after dental surgery in patients taking antiplatelet medications. Conversely, the risk for thrombotic complications after interruption of antiplatelet therapy for dental procedures apparently is significant, although small. When a clinician is faced with a decision to continue or interrupt antiplatelet therapy for a dental surgical patient, the decision comes down to “bleed or die.” That is, there is a remote chance that continuing antiplatelet therapy will result in a (nonfatal) bleeding problem requiring more than local measures for hemostasis versus a small but significant chance that interrupting antiplatelet therapy will result in a (possibly fatal) thromboembolic complication. The decision is simple: It is time to stop interrupting antiplatelet therapy for dental surgery.     

Platelet receptor redox regulation

A large number of patients require antiplatelet therapy (mainly aspirin and/or clopidogrel). Recent studies suggest that the combination of these agents is useful in patients with acute coronary syndrome and after percutaneous coronary intervention with stent placement. On the other hand, bleeding complications, most of which arise from the upper gastrointestinal (UGI) tract, can limit the use of antiplatelet drugs. Clopidogrel appears to be associated with fewer UGI side effects and bleeding compared with aspirin. However, a history of previous UGI bleeding is a major risk factor for clopidogrel-associated bleeding. The use of proton-pump inhibitors (PPIs) decreases the rate of UGI bleeding in patients receiving aspirin or clopidogrel. Furthermore, a recent study suggested that the administration of low-dose aspirin plus high-dose esomeprazole (a potent PPI) was associated with fewer episodes of UGI bleeding than clopidogrel alone in patients with a history of recent UGI haemorrhage. However, this study had several limitations and its results should be cautiously extrapolated into clinical practice. The combination of aspirin plus clopidogrel increases the risk of UGI bleeding. Unfortunately, there are no data on the effect of PPI prophylaxis in this setting. Available evidence suggests that where aspirin and/or clopidogrel are to be started or continued in patients with a recent history of UGI ulceration or bleeding (after ulcer healing and eradication of H. pylori infection), treatment with a PPI is a useful precaution. The patients should also be carefully monitored for recurrence of UGI bleeding.     

Practical issues, limitations, and periprocedural management of the NOAC’s

The recent introduction of new oral anticoagulants or novel target specific oral anticoagulants (TSOA’s) is likely to have a major impact in the years ahead. Many large clinical trials have been published in the past few years showing these agents are generally safe and effective in several clinical settings including acute venous thromboembolic disease, prophylaxis in the postoperative setting, prevention of thromboembolism in patients with atrial fibrillation, and in the management of acute coronary syndromes. Reported rates of overall and intracranial bleeding are lower compared to oral vitamin K antagonists. Other major advantages of oral direct thrombin inhibitors (dabigatran) and Xa inhibitors (rivaroxaban and apixaban) include rapid onset and offset of action and predictable pharmacodynamics with relatively wide therapeutic window allowing for unmonitored drug use. The relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use of these agents. In this review we focus on some practical issues related to TSOA’s including some limitations, potential complications, considerations to be made for certain patient populations, periprocedural management and issues pertaining to transition to and from these novel agents.     

Anticoagulation for Mechanical Heart Valves in Patients with and without Atrial Fibrillation

Surgical replacement of a native valve with a biological or mechanical prosthesis is the definitive treatment for many forms of advanced valvular heart disease. Mechanical heart valves are less prone to structural deterioration compared with bioprostheses, but require chronic oral anticoagulation to prevent thromboembolic events. Thromboembolic risk varies based on patient-related risk factors, including atrial fibrillation, advanced age, low ejection fraction, and hypercoagulability. Other important correlates of high thromboembolic risk include valve design, valve position, anticoagulation variability, and time from surgery. Clinical management is further complicated when antithrombotics may need to be interrupted or altered during surgery or pregnancy. At present, vitamin K antagonists are the only approved agents for thromboprophylaxis but are limited because of a narrow therapeutic window and requirement for frequent monitoring. Novel anticoagulants, including inhibitors of factor IIa and Xa, are currently being evaluated and may emerge as alternatives to vitamin K antagonists.     

Endoscopic findings and management of dengue patients with upper gastrointestinal bleeding

There are 100 million cases of dengue infection, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually due to dengue worldwide. Gastrointestinal bleeding is the most common type of severe hemorrhage in dengue fever. However, there are no reports about the clinical applications of endoscopic therapy for upper gastrointestinal bleeding (UGI) in dengue patients. From June 17, 2002 to January 30, 2003, 1,156 patients with confirmed dengue virus infection were treated at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We analyzed those patients who had received endoscopic therapy for UGI. The characteristic endoscopic findings, therapeutic courses, and amount of blood component transfused were collected from their charts for statistical analysis. Among the 1,156 dengue patients, 97 (8.4%) had complications of UGI bleeding during hospitalization. The endoscopic findings included hemorrhagic (and/or erosive) gastritis in 67% of the patients, gastric ulcer in 57.7%, duodenal ulcer in 26.8%, and esophageal ulcer in 3.1%. Of the 73 patients with peptic ulcer, 42 (57.5%) met the endoscopic criteria (recent hemorrhage) for endoscopic hemostasis therapy. Peptic ulcer patients with recent hemorrhage required more transfusions with packed red blood cells (P = 0.002) and fresh frozen plasma (P = 0.05) than those without recent hemorrhage. Among these 42 patients with recent hemorrhage, endoscopic injection therapy was conducted in 15 patients (group A). The other 27 patients (group B) did not receive endoscopic therapy. After endoscopy, patients in group A required more transfusions with packed red blood cells (P = 0.03) and fresh frozen plasma (P = 0.014) than did patients in group B. There were no significant differences between groups A and B in duration of hospital stay and amounts of transfused platelet concentrate after endoscopy. Medical treatment with blood transfusion is the mainstay of management of UGI bleeding in dengue patients. Patients having peptic ulcer with recent hemorrhage require more transfusions with packed red blood cells and fresh frozen plasma for management of UGI bleeding than those without recent hemorrhage. However, when peptic ulcer with recent hemorrhage is encountered during the endoscopic procedure, endoscopic injection therapy is not an effective adjuvant treatment of hemostasis in dengue patients with UGI bleeding.     

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.     

Treatment of drug-induced immune thrombocytopenias

Several therapeutic agents can cause thrombocytopenia by either immune-mediated or non-immune-mediated mechanisms. Non-immune-mediated thrombocytopenia is due to direct toxicity of drug molecules to platelets or megakaryocytes. Immune-mediated thrombocytopenia, on the other hand, involves the formation of antibodies that react to platelet-specific glycoprotein complexes, as in classic drug-induced immune thrombocytopenia (DITP), or to platelet factor 4, as in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT). Clinical signs include a rapid drop in platelet count, bleeding or thrombosis. Since the patient''s condition can deteriorate rapidly, prompt diagnosis and management are critical. However, the necessary diagnostic tests are only available in specialized laboratories. Therefore, the most demanding step in treatment is to identify the agent responsible for thrombocytopenia, which often proves difficult because many patients are taking multiple medications and have comorbidities that can themselves also cause thrombocytopenia. While DITP is commonly associated with an increased risk of bleeding, HIT and VITT have a high mortality rate due to the high incidence of thromboembolic complications. A structured approach to drug-associated thrombocytopenia/thrombosis can lead to successful treatment and a lower mortality rate. In addition to describing the treatment of DITP, HIT, VITT, and vaccine-associated immune thrombocytopenia, this review also provides the pathophysiological and clinical information necessary for correct patient management.     

Heparin bridge therapy and post-polypectomy bleeding

AIM To identify risk factors for post-polypectomy bleeding(PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS PPB occurred in 29(3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210(26.6%)patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB(P 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB(P 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.     

Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (ÖGHO) and Society of Thrombosis and Haemostasis Research (GTH e.V.)

Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) like polycythemia vera and essential thrombocythemia are at increased risk of arterial and venous thrombosis. Strategies of prevention may consist of platelet aggregation inhibitors and/or cytoreductive agents depending on the underlying disease and the individual risk. Clinical evidence for management of acute venous thromboembolic events in MPN patients is limited. Modality and duration of therapeutic anticoagulation after venous thrombosis has to be evaluated critically with special regard to the increased risk for spontaneous bleeding events associated with the underlying diseases. Both for therapy of the acute event and for secondary prophylaxis, low-molecular-weight heparins should preferentially be used. A prolongation of the therapeutic anticoagulation beyond the usual 3 to 6 months can only be recommended in high-risk settings and after careful evaluation of potential risks and benefits for the individual patient. New direct oral anticoagulants (NOAC) should not preferentially be used due to lack of clinical experience in patients with MPN and potential drug interactions (e.g. with JAK inhibitors). Consequent treatment of the underlying myeloproliferative disease and periodical evaluation of the response to therapy is crucial for optimal secondary prophylaxis of thromboembolic events in those patients.     

Drug therapy for non-variceal upper gastrointestinal bleeding. Assessment of options

The efficacy of somatostatin and octreotide have been widely studied in the control of bleeding from oesophageal varices. It has also been suggested that these drugs may be useful for the control of non-variceal upper gastrointestinal (UGI) bleeding, including that from peptic ulcers. In approximately 80% of patients presenting with non-variceal UGI bleeding, haemorrhage ceases spontaneously and does not recur. However, the remaining 20% of patients require active treatment. Results from recent studies have indicated that somatostatin is an effective treatment for the control of non-variceal UGI bleeding in high-risk patients, i.e. those in whom haemorrhage does not cease spontaneously or is likely to recur. In contrast there is no good evidence available at present to support a role for octreotide, histamine (H(2) antagonists) or proton pump inhibitors in this indication. The efficacy of somatostatin in controlling bleeding in patients with non-variceal UGI bleeding at high risk of mortality upon admission, or rebleeding following endoscopy, coupled with an excellent safety and tolerability profile, suggests it may be a valuable therapeutic option in the management of non-variceal bleeding.