Safety of pancreatic surgery with special reference to antithrombotic therapy:A systematic review of the literature

BACKGROUND Postpancreatectomy hemorrhage(PPH)is the most severe type of complication after pancreatic surgery,although the effect of antithrombotic therapy(ATT)on PPH is largely unknown.The safety and efficacy of chemical thromboprophylaxis for venous thromboembolism(VTE)remains controversial.AIM To elucidate the effect of ATT on PPH.METHODS Published articles between 2013 and 2020 were searched from PubMed and Google Scholar,and after careful reviewing of all studies,studies concerning ATT and pancreatic surgery were included.Data such as study design,type of surgical procedures,type of antithrombotic drugs,and surgical outcome were extracted from the studies.RESULTS Nineteen published articles with a total of 37863 patients who underwent pancreatic surgery were included in the systematic review.Fourteen were cohort studies,with only three being prospective in nature.Two studies demonstrated that in patients receiving chronic ATT,which were mostly managed by heparin bridging,the risk of PPH was higher compared with those without ATT,and one study showed that patients with direct-acting oral anticoagulants managed by heparin bridging had significantly higher postoperative bleeding rates than others.The remaining six studies reported that pancreatic surgery can be safely performed in patients receiving chronic ATT,even under preoperative aspirin continuation.Concerning chemical thromboprophylaxis for VTE,most studies have shown a potentially high risk of PPH in patients undergoing chemical thromboprophylaxis;however,its effectiveness against VTE has not been statistically demonstrated,particularly among Asian patients.CONCLUSION Pancreatic surgery in chronically ATT-received patients can be safely performed without an increase in the occurrence of PPH,although the safety and efficacy of chemical thromboprophylaxis for VTE during pancreatic surgery is still controversial.Further investigation using reliable studies with good design is required to establish definite protocols or guidelines.

Safety of liver resection in patients receiving antithrombotic therapy:A systematic review of the literature

BACKGROUND Little is unknown about the effect of chronic antithrombotic therapy(ATT)on bleeding complication during or after hepatectomy.In addition,the safety and effectiveness of chemical prevention for venous thromboembolism(VTE)is still controversial.AIM To clarify the effect of ATT on thromboembolism and bleeding after liver resection.METHODS Articles published between 2011 and 2020 were searched from Google Scholar and PubMed,and after careful reviewing of all studies,studies concerning ATT and liver resection were included.Data such as study design,type of surgery,type of antithrombotic agents,and surgical outcome were extracted from the studies.RESULTS Sixteen published articles,including a total of 8300 patients who underwent hepatectomy,were eligible for inclusion in the current review.All studies regarding patients undergoing chronic ATT showed that hepatectomy can be performed safely,and three studies have also shown the safety and efficacy of preoperative continuation of aspirin.Regarding chemical prevention for VTE,some studies have shown a potentially high risk of bleeding complications in patients undergoing chemical thromboprophylaxis;however,its efficacy against VTE has not been shown statistically,especially among Asian patients.CONCLUSION Hepatectomy in patients with chronic ATT can be performed safely without increasing the incidence of bleeding complications,but the safety and effectiveness of chemical thromboprophylaxis against VTE during liver resection is still controversial,especially in the Asian population.Establishing a clear protocol or guideline requires further research using reliable studies with good design.

Association of antithrombotic therapy with postoperative rebleeding in patients with cerebral amyloid angiopathy

Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults.Although open hematoma removal may be performed for severe subcortical hemorrhage,its safety in patients with cerebral amyloid angiopathy has not been established,and postoperative rebleeding may occur.Therefore,this study aimed to investigate factors associated with postoperative rebleeding.Methods Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan,we examined 109 patients with subcortical hemorrhage who met the inclusion criteria.After excluding 30 patients whose tissue samples were unsuitable for the study,the final study cohort comprised 79 patients.Results Of the 79 patients,50(63%)were diagnosed with cerebral amyloid angiopathy(cerebral amyloid angiopathy group)and 29(37%)were not diagnosed with noncerebral amyloid angiopathy(noncerebral amyloid angiopathy group).Postoperative rebleeding occurred in 12 patients(24%)in the cerebral amyloid angiopathy group and in 2 patients(7%)in the noncerebral amyloid angiopathy group.Preoperative prothrombin time-international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group(odds ratio=42.4,95%confidence interval=1.14-1578;p=0.042 and odds ratio=1.005,95%confidence interval=1.001-1.008;p=0.007,respectively).Conclusions Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy,particularly warfarin therapy,are at a high risk of postoperative rebleeding.Trial registration Registry and Registration Number of the study:19-220,2019/12/23,retrospectively registered.

Triple antithrombotic therapy versus double antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients requiring chronic oral anticoagulation： a meta-analysis

Background Whether an addition of OAC to double antiplatelet therapy for patients with an indication of chronic oral anticoagulation undergoing PCI-S may improve clinical outcomes is still debated. This meta-analysis aimed to update and re-compare the benefits and risks of triple antithrombotic therapy （TT） with double anti-platelet therapy （DAPT） after in patients who requiring oral anticoagulation after percutaneous coronary interventions with stenting （PCI-s）. Methods Ten reports of observational retrospective or prospective studies were retrieved, including a total of 6296 patients, follow-up period ranging from 1 year to 2 years. Results Baseline characteristics were similar in both groups. The main finding of this study is the overall incidence of major adverse cardiovascular events （MACE）, myocardial infarction （MI） and stent thrombosis was comparable between two groups. Patients with TT was associated with significant reduction in ischemic stroke （OR： 0.27; 95% CI： 0.13-0.57; P=0.0006） as compared to DAPT. We reaffirmed triple therapy significantly increased the risk of major bleeding （OR： 1.47; 95% CI： 1.22-1.78; P 〈0.0001） and minor bleeding （OR： 1.55; 95% CI： 1.07-2.24; P=-0.02）. Conclusions Triple therapy is more efficacious in reducing the occurrence of ischemic stroke in PCI-s patients with an indication of chronic oral anticoagulation （OAC）, compared with DAPT. However, it significantly increased major and minor risk of bleeding. It is imperative that further prospective randomized controlled trials are required to define the best therapeutic strateav for patients with an indication of chronic OAC underaoina PCI-s.

Situation of antithrombotic therapy in elderly patients with atrial fibrillation and acute coronary syndrome

Background Atrial fibrillation is the most common cardiac arrhythmia in clinical practice. The study examines the situation of antithrombotic therapy in elderly patients （more than 60 years old） with non-valvular atrial fibrillation （NVAF） and acute coronary syndrome （ACS） / percutaneous coronary intervention （PCI）. Methods This study enrolled 381 elderly patients Emean age （69.95 ± 8.41） years; 289 males, 92 femalesl with NVAF and ACS/PCI between January 2006 and September 2013. According to clinical data, these patients were categorized into 4 groups： triple therapy （TT） group, dual antiplatelet therapy （DAT） group, vitamin K antagonist （VKA） plus single antiplatelet therapy （SAT） group and VKA group. According to score of CHA2DS2-VASc and HAS-BLED, all the patients were divided into 4 combinations. Statistical methods were used to analyze the situation of antithrombotic therapy and potential associations between the different combinations. Results 38 patients （9.97%） received TT and 300 patients （78.74%） received DAT. TT was received in 20 patients with CHA2DS2-VASc ≥2 and HAS-BLED ≥3, and 16 patients with CHA2DS2- VASc≥2 and HAS-BLED 〈 3. Conclusions Elderly patients who suffered NVAF and ACS/PCI were with high risk of stroke and low risk of bleeding. Majority of these patients received DAT instead of TT.

Optimal Antithrombotic Therapy after Implantation of a Transcatheter Aortic Valve: Warfarin, Aspirin, or Non-Vitamin K Antagonist Oral Anticoagulants? A Systematic Review and Meta-Analysis

Objective:Diverse antithrombotic strategies were applied to patients undergoing aortic valve replacement.However,the optimal therapeutic regimen for patients undergoing transcatheter aortic valve implantation/replacement(TAVI/TAVR)remains unclear.The purpose of this study was to compare the efficacy and safety of various antithrombotic therapies following TAVI/TAVR.Methods:Relevant clinical trials evaluating the effect of anticoagulation or antiplatelet regimens on patients after TAVI/TAVR from inception to September 2020 were identified using the PubMed,EMBASE,and the Cochrane Library databases.The inclusion criteria including(1)all patients underwent TAVI/TAVR;(2)the interventions were antithrombotic strategies that prevent the occurrence of thrombotic events in patients;(3)randomized controlled trials or prospective observational studies;and(4)investigation of at least 1 outcome with a follow-up period of≥3 months.The exclusion criteria including(1)research content was identical or irrelevant to the purpose of the present study;(2)lack of the required outcome index or availability of fragmentary original information;and(3)the full text is not available.The major outcomes were all-cause mortality,thromboembolic complications,and bleeding events.The Cochrane Collaboration’s tool and the Newcastle-Ottawa Scale were used for assessing the risk of bias in included studies.Results:Thirteen studies(3 randomized controlled trials and 10 non-randomized studies)were identified,with a total of 23,497 patients.Four studies compared direct oral anticoagulants(DOACs)with warfarin,1 study compared aspirin with warfarin,6 studies compared aspirin plus clopidogrel(dual antiplatelet therapy(DAPT))with aspirin monotherapy,and 2 studies compared DAPT and aspirin monotherapy with warfarin concurrently.There were no significant differences found between the DOAC and warfarin groups regarding all-cause mortality(risk ratio(RR):1.03;95%confidence interval(CI):0.65–1.64;P=0.909;Phet=0.105),clinical adverse events(RR:1.59;95%CI:0.99–2.58;P=0.057;Phet=0.738),or bleeding events(RR:0.93;95%CI:0.78–1.11;P=0.437;Phet=0.338).The rates of all-cause mortality(RR:0.71;95%CI:0.54–0.93;P=0.012;Phet=0.845)and bleeding events(RR:0.43;95%CI:0.22–0.83;P=0.012;P_(het)=0.569)were lower in the aspirin group versus the warfarin group;however,there was no difference in the rate of clinical adverse events(RR:0.38;95%CI:0.14–1.07;P=0.068;Phet=0.593).The DAPT group had an advantage versus the aspirin group in all-cause mortality(RR:0.89;95%CI:0.82–0.98;P=0.013;Phet=0.299);however,the incidence of bleeding events(RR:2.06;95%CI:1.39–3.07;P<0.001;Phet=0.001)exhibited an increasing trend.Notably,there was a slight decrease in the incidence of clinical adverse events(RR:1.09;95%CI:0.94–1.26;P=0.268;Phet=0.554).Conclusion:The present meta-analysis integrates the latest published results on antithrombotic strategies in patients after TAVI/TAVR.Aspirin showed a favorable risk-benefit profile versus warfarin,with lower rates of all-cause mortality and bleeding events.Although DAPT was also associated with a significantly lower rate of all-cause mortality,it was linked to a higher incidence of bleeding events.The DOACs did not show significant benefits compared with warfarin.Some certain limitations should be noted,such as different types of trails produce heterogeneity and finite inclusion of TAVI/TAVR patients increased selection bias.

Atrial fibrillation and coronary artery disease:An integrative review focusing on therapeutic implications of this relationship

The incidence of both atrial fibrillation(AF)and coronary artery disease(CAD)increases with advancing age.They share common risk factors and very often coexist.Evidence points to an intricate relationship between atrial tissue excitability and neuronal remodeling with ischemia at the microcirculatory level.In this review,we delineated this complex relationship,identified a common theme between the two,and discussed how the knowledge of this relationship translates into a positive and meaningful impact in patient management.Recent research indicates a high prevalence of CAD among AF patients undergoing coronary angiography.Further,the incidence of AF is much higher in those suffering from CAD compared to age-matched adults without CAD underlying this reciprocal relationship.CAD adversely affects AF by promoting progression via re-entry and increasing excitability of atrial tissue as a result of ischemia and electrical inhomogeneity.AF in turn accelerates atherosclerosis via endothelial dysfunctional and inflammation and together with enhanced thrombogenicity and hypercoagulability contribute to micro and macrothrombi throughout cardiovascular system.In a nutshell,the two form a vicious cycle wherein one disease promotes the other.Most AF recommendations focuses on rate/rhythm control and prevention of thromboembolism.Very few studies have discussed the importance of unmasking coexistent CAD and how the treatment of underlying ischemia will impact the burden of AF in these patients.Inflammation and endothelial dysfunction remain central to both disease processes and form a handsome therapeutic target in the management of the two diseases.The relationship between AF and CAD is complex and much more than mere coincidence.The two diseases share common risk factor and pathophysiology.Hence,it is impractical to treat them in isolation.Accordingly,we share the implications of managing underlying ischemia and inflammation to positively impact and improve quality of life among AF patients.

Hemorrhagic shock due to submucosal esophageal hematoma along with mallory-weiss syndrome:A case report

BACKGROUND Esophageal submucosal hematoma is a rare condition.Although the exact etiology remains uncertain,vessel fragility with external factors is believed to have led to submucosal bleeding and hematoma formation;the vessel was ruptured by a sudden increase in pressure due to nausea,and the hematoma was enlarged by antiplatelet or anticoagulant therapy.Serious conditions are rare,with a better prognosis.We present the first known case of submucosal esophageal hematoma-subsequent hemorrhagic shock due to Mallory-Weiss syndrome.CASE SUMMARY A 73-year-old female underwent endovascular treatment for an unruptured cerebral aneurysm.The patient received aspirin and clopidogrel before surgery and heparin during surgery,and was well during the surgery.Several hours after returning to the ICU,she complained of chest discomfort,vomited 500 m L of fresh blood,and entered hemorrhagic shock.Esophageal submucosal hematoma with Mallory-Weiss syndrome was diagnosed through an endoscopic examination and computed tomography.In addition to a massive fluid and erythrocyte transfusion,we performed a temporary compression for hemostasis with a Sengstaken-Blakemore(S-B)tube.Afterwards,she became hemodynamically stable.On postoperative day 1,we performed an upper gastrointestinal endoscopy and confirmed no expansion of the hematoma nor any recurring bleeding;therefore,we removed the S-B tube and clipped the gastric mucosal laceration at the esophagogastric junction.We started oral intake on postoperative day 10.The patient made steady progress,and was discharged on postoperative day 33.CONCLUSION We present the first known case of submucosal esophageal hematoma subsequent hemorrhagic shock due to Mallory-Weiss syndrome.

Advances in antithrombin therapy for ST-elevation myocardial infarction

Thrombin is a pivotal molecule in acute myocardial infarction ( Ml) because of its extensive procoagulant and prothrombotic actions. Antithrombin therapy is an important component of the pharmacotherapy for acute Ml. The standard agent used in clinical practice, unfractionated heparin (UFH), is associated with the disadvantages of variable anticoagulant effect, inability to inhibit clot-bound thrombin, neutralization by platelet factor 4, and the propensity to cause thrombocytopenic complications. Novel thrombin inhibitors have been developed to overcome these disadvantages. Although possessing the property of inhibiting both fluid-phase and clot-bound thrombin, the direct thrombin inhibitor hirudin has been shown to give marginal benefits over UFH as adjunct to fibrinolysis in ST-elevation Ml. Bivalirudin, another direct thrombin inhibitor, is able to reduce reinfarction in patients treated with streptokinase and is a new anticoagulant treatment option in this setting. The pharmacokinetic characteristics of better availability, longer half-life, and dose-independent clearance together with the ability of inhibiting both thrombin generation and activity make the low-molecular-weight heparins (LMWHs) an attractive alternative to UFH. The favorable benefit/risk profile of the LMWHs as adjunct to different generations of fibrinolytic agents is setting the stage for larger clinical trials to confirm their role as the antithrombin agent of choice for STEMI.

Comparison of Aspirin and Naoxintong Capsule(脑心通胶囊)with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase

Objective： To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule（脑心通胶囊, NXT） and aspirin with adjusted-dose warfarin in Chinese elderly patients（over 65 years） with nonvalvular atrial fibrillation（NVAF） and genetic variants of vitamin K epoxide reductase（VKORC1）, who are at high-risk of thromboembolism. Methods： A total of 151 patients, with NVAF and AA genotype of VKORC1-1639（a sensitive genotype to warfarin） and a CHA2 DS2-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin（100 mg/day） and NXT（1.6 g thrice a day） or adjusted-dose warfarin [international normalized ratio 2.0–3.0）. The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. Results： Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding（secondary event） in the combination therapy group was lower than that in the adjusted-dose warfarin group（0% vs. 7.9%, odds ratio： 0.921, 95% confidence interval： 0.862–0.984, P=0.028）. Conclusions： Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin.（No. ChiC TR-TRC-13003596）

State of the art contemporary treatment of patients with ST elevationmyocardial infarction： pre- and in-hospital organization, devices anddrugs

Objective To review the presentation,diagnosis and recent developments in the pharmacological and invasive treatment of ST elevation myocardial infarction (STEMI) with a special focus on health-care organization in order to increase accessibility of primary pemutaneous coronary intervention (PCI).Data sources Data were obtained from English publications on STEMI treatment.No formal systematic review was conducted,but an effort was made to be comprehensive.Study selection Studies were selected if they contained data relevant to the topic.Preferably,data from clinical randomized trials,meta-analyses,guidelines and a few recent reviews are referenced.Results The described clinical approach to acute myocardial infarction (AMI) has been a continuum of scientific results and translation into clinical practice over the last four decades since the advent of thrombolytic reperfusion.This has resulted in a dramatic in-hospital mortality decrease from 30% in the 1960s to the present 5%.The biggest survival benefits have undoubtedly been achieved after the advent of reperfusion strategies.In contemporary treatment of STEMI,additional treatment effects on survival have to be sought in the very early admission phase,as the current mortality hazard drops significantly after the first critical days to continuously very low levels after discharge.Conclusions Optimal treatment of STEMI patients is best performed with a widely accessible reperfusion strategy,preferably primary PCI,with contemporary peri-procedural anti-thrombotic treatment and device implantation.Accessibility of reperfusion strategies is increased by efficient STEMI networks applying prehospital triage with digital tele-transmission of electrocardiograms (ECGs) and seamless patient transitions between health-care unities.Efficient treatments of complicated STEMI with out-of hospital cardiac arrest and/or cardiogenic shock underline the necessity of structured referral systems,preferably immediately after the initial STEMI diagnosis。

Current Use of Oral Anticoagulants and Prognostic Analysis in Patients with Atrial Fibrillation Undergoing Coronary Stenting

Background： It is currently believed that triple oral antithrombotic therapy in patients with atrial fibrillation （AF） after percutaneous coronary intervention （PCI） should be recommended if there are no contraindications. However, selecting triple therapy for AF patients undergoing PCI is still challenging when bleeding risk is considered. This study aimed to investigate the current use of oral anticoagulants （Vitamin K antagonists [VKA]） and perform prognostic analysis in real-world patients with AF undergoing coronary stenting. Methods： A total of 276 consecutive coronary artery disease （CAD） patients with or without AF undergoing coronary stenting were retrospectively evaluated and analyzed. The univariate and multivariate analyses were conducted to explore the current use of VKA and prognosis of patients with AF undergoing coronary stenting. The primary end-point was composite of all-cause death, nonfatal recurrent myocardial infarction, stroke, serious bleeding events, unplanned repeat revascularization, and worsening heart failure at 12-month follow-up after coronary stenting. Results： AF patients undergoing coronary stenting have more clinical concomitant diseases. Only 9.0% AF patients after coronary stenting received triple antithrombotic therapy （VKA, aspirin, and clopidogrel） at discharge. AF was independently associated with increased risk of the 12-month composite end-points （relative risk = 5.732, 95% confidence interval 1.786-18.396, P = 0.003）. Conclusions： In real-life AF patients undergoing coronary stenting, guideline-recommended VKA was less used. AF patients had adjusted worse prognosis during 12-month follow-up after discharge. It is of utmost importance to improve the current status of oral anticoagulants use.

A Comparative Study on Post-intervention Use of Tirofiban or Enoxaparin in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Objectives To evaluate the efficacy and safety of post procedure use of platelet glycoprotein Ⅱb/Ⅲ a receptor in- hibitor （PGI） or low molecular weight heparin （LMWH） in patients with acute coronary syndrome （ACS） undergoing dual anti-platelet loading therapy and percutaneous coronary intervention （PCI）. Methods This was a prospective randomized grouping controlled study in 174 patients with ACS received aspirin 300 mg plus clopidogrel 600mg loading before PCI. After procedure, patients were randomized to intravenous tirofiban for 12 -24 hours （tirofiban group） or subcutaneous enoxaparin for 5 days （enoxaparin group）. Cardiac ischemic events, major bleeding complications, minor bleeding complications, thrombocytopenia, and vascular access complications in both groups were investigated. Results Cardiac ischemic events, major bleeding complications, minor bleeding complications, thrombocytopenia, and vascular access complications in tirofiban group were 8.0% , 3.4% , 6.8% , 3.4% , and 3.4% , respectively. In enoxaparin group, aforementioned event rates were 7%, 2. 3%, 6. 0%, 2. 3%, and 5.8%, respectively. No statistical significance was found between two groups. Conclusions In the setting of dual anti-platelet medication loading and PCI for the treatment of ACS, it is effective to use tirofiban or enoxaparin for aggressive post procedure antithrombotic therapy. It comes with a very low major bleeding complication rate. Use of GPI for 12 to 24 hours was comparable to use of LMWH for 5 days in efficacy and safety.