Cessation Of Anticoagulation Research Articles

Managing Intracranial Hemorrhage in Patients with a Durable Continuous Flow Left Ventricular Assist Device

Background
 While intracranial hemorrhage (ICH) is a known complication of left ventricular assist device (LVAD) support, and is associated with high morbidity and mortality, optimal care pathways have neither been elucidated nor reported. We describe management of LVAD patients following ICH, with a focus on anticoagulation, operative interventions, care team designation, complications, and outcomes.
 Methods
 We retrospectively reviewed all durable continuous-flow LVAD implantations at our academic medical center from January 2007 to July 2018. Patients who experienced ICH after LVAD were identified. We defined baseline and ICH characteristics, medical and surgical interventions, care teams, and outcomes including death, device thrombosis, ischemic stroke, and hemorrhage expansion.
 Results
 A total of 321 patients underwent LVAD implantation during the study period, and 27 (8%) developed ICH (17 intraparenchymal, 7 subdural, 2 subarachnoid, 1 intraventricular) while on support. Twenty-five were anticoagulated at onset of bleed. Of those, 13 were managed with immediate cessation of anticoagulation and administration of reversal products (Group A). Group A had a median of 6 days off anticoagulation and 60 days of follow up with 1 patient (8%) developing device thrombosis at day 8, 1 (8%) developing subsequent ischemic stroke at day 14, and 4 (31%) with ICH expansion. Seven patients had anticoagulation stopped at onset of bleed without administration of reversal products (Group B). With a median of 2 days off anticoagulation and 2 days of follow up, no patients in Group B developed ischemic stroke or device thrombosis while 1 (14%) had ICH expansion. Five patients had anticoagulation continued at onset of bleed (Group C) with a median follow up of 330 days. One (20%) developed device thrombosis at day 5 while 2 (40%) developed ICH expansion. Four patients with subdural hemorrhage underwent Burr hole drainage with all 4 surviving to discharge. Two patients with intraparenchymal hemorrhage underwent open craniotomy with neither surviving to discharge. An interdisciplinary discussion occurred in all cases. Following ICH, only one-third of patients in the study survived to 6 months.
 Conclusion
 LVAD patients who experience an ICH have variable outcomes. Their care is multidisciplinary and can involve operative intervention. The discontinuation and reversal of anticoagulation is generally well-tolerated, with a low risk for early device thrombosis. Like for many hemorrhagic complications of LVADs, ICH often persists or worsens. Additional investigation is needed to elucidate the most optimal management strategies.

Safety of oral anticoagulants on experimental brain microbleeding and cognition

This study aims at determining the ability of clinical-based doses of four oral anticoagulants to transform the onset of a cerebral microhemorrhages (CMH) burden into a symptomatic intracerebral hemorrhage (ICH) in the healthy brain, and precipitate cognitive impairment. Wild-type mice were anticoagulated for 10 days using apixaban, rivaroxaban or dabigatran as direct oral anticoagulants (DOACs), or warfarin as vitamin K-antagonist. Meanwhile, a burden of ∼20 CMHs was induced in the Sylvian territory by intra-carotid injection of cyclodextrin nanoparticles. At bleeding onset, only warfarin provoked deadly hematoma, and dramatically increased mortality (+45%). All the DOACs enhanced CMH burden through a greater number of intermediate-sized microhemorrhages (+80% to +180%). Although silent at onset, both baseline- and anticoagulant-enhanced CMH burdens increased mortality (+11% to +58%) along the following year without statistical difference among groups, and despite cessation of anticoagulation and absence of CMH progression or transformation into ICH. All survivor mice exhibited reduction in visual recognition memory from 9 months. In the healthy brain, DOACs preserve the onset of microhemorrhages from transformation into ICH, and do not precipitate cognitive impairment despite enhancement of CMH burden. High CMH burdens should however be considered for early detection and preventive memory care apart from anticoagulation decisions.

A Trial of Complete Withdrawal of Anticoagulation Therapy in the Heartmate 3 Pump

Summary of Objectives The HeartMate 3 Left Ventricular Assist System has demonstrated absence of confirmed de-novo pump thrombosis and reduction in stroke. However, bleeding related adverse events persist under standard anticoagulation targeting a INR range of 2.0-3.0. In an initial experience we demonstrated safety of transition to low intensity anticoagulation (INR target 1.5-1.9, n=15, follow up of at least 6 months). Whether complete cessation of anticoagulation maintains “thromboresistance” in the HeartMate 3 pump remains unknown. Methods We previously reported on a strategy of low-intensity warfarin anticoagulation in patients implanted with HeartMate 3 (J Heart Lung Transplant. 2018;37(5):579-586). Following completion of this study phase, a staged trial was approved by the single site's ethics committee and registered as NCT03704220. All patients enrolled in the low intensity warfarin study (target INR of 1.5-1.9) were considered eligible for enrollment in the “anticoagulation withdrawal” study, if they were continuing on long-term support. All patients had to meet safe eligibility criteria including pump speed reduction to facilitate aortic valve opening (to avoid root thrombus), absence of thrombus in the pre-pump cardiac system, and absence of signs of poor unloading at reduced device speed. Careful surveillance for pump thrombosis was algorithmically mandated with biomarker and serial pump log file analyses. If enrolled, they were withdrawn from warfarin therapy and followed for survival free of pump thrombosis, disabling stroke or major bleeding for at least 3 months as the primary safety end point. Endpoints Enrollment and follow up in the low intensity anticoagulation study has been reported (n=15); 13 men, mean age 57 years (18-72), with intended goal of therapy of either BTT or DT, INTERMACS Profile mean 3 (2-5), Cardiac Index mean 1.62 l/min/m2. Of 10 patients followed beyond 1 year on reduced anticoagulation, 5 patients have qualified for complete withdrawal of anticoagulation and the safety endpoint analysis will be completed prior to the ISHLT meeting in March 2019. This pivotal study is the first indication-independent anticoagulation withdrawal study in the HeartMate 3 designed to establish thrombo-resistance for the device and form the rationale for a large scale multicenter trial.

Persistence and outcomes of non-vitamin K antagonist oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation.

To compare persistence and outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in Chinese patients with non-valvular atrial fibrillation (AF). Given the unpredictable warfarin response and the costliness of NOACs, more research is needed to clarify which drug enjoys better persistence and outcomes, helping to provide personalised care for patients. A prospective cohort study. Chinese patients taking NOACs or warfarin from March 2016-April 2018 were followed up by telephone or outpatient visit at 3, 6months and half a year thereafter. Anticoagulant persistence and outcomes including stroke and bleeding were collected. We used Cox regression to analyse data. This study was reported according to the STROBE guideline. A total of 344 patients were enrolled; 146 patients received NOACs including dabigatran and rivaroxaban, and 198 patients received warfarin. Persistence with anticoagulants was low and dropped sharply at the third month. Patients on NOACs had worse persistence at 3, 6 and 12months than those on warfarin. There was no difference in the incidence of ischaemic stroke and bleeding between groups, although ischaemic stroke and major bleeding occurred less frequently in the NOACs group. Paroxysmal AF, no heart failure and no stroke were predictors of NOACs non-persistence. Prior catheter ablation and no diabetes were associated with poor persistence of warfarin. The main reason for anticoagulant cessation was patient preference. Chinese patients taking NOACs had lower persistence, similar rate of ischaemic stroke and bleeding compared with those on warfarin. Further inventions are needed to improve persistence in Chinese patients on NOACs. Anticoagulation should highlight both persistence and outcomes emphasising personalised care of different drugs. Further interventions to improve persistence should be developed based on causes and risk factors and carried out in the third month of therapy.

To Maintain or Cease Non-Vitamin K Antagonist Oral Anticoagulants Prior to Minimal Bleeding Risk Procedures: A Review of Evidence and Recommendations.

For procedures associated with minimal bleeding risk, there are data and experience to support the practice of continuing vitamin K antagonists rather than interrupting therapy, to prevent exposing patients to the undue risk of developing thromboembolism during anticoagulation cessation. Despite the increasing use of non-vitamin K oral anticoagulants (NOACs), there is little evidence to guide the management of these drugs around minimal bleeding risk procedures. This review examines and discusses the major society guidelines and recommendations addressing the management of NOACs around minimal bleeding risk procedures. Additionally, it summarizes the existing evidence, and highlights the gaps in knowledge where evidence is not yet available. Finally, recommendations are made to assist the proceduralist deal with this area of limited evidence.

Heparin bridge is associated with more post-polypectomy bleeding and emergency department visits among anticoagulated patients

Background:Among patients undergoing colonoscopy, anticoagulants are usually stopped and are sometimes substituted by a heparin bridge (hep-bridge). We aimed to assess adverse events associated with hep-bridge compared to temporary cessation of anticoagulants (no-bridge).Methods:This was a single-center, retrospective cohort study that included anticoagulated patients undergoing colonoscopy between 2013 and 2016 at a Veterans Affairs Medical Center. In the no-bridge cohort, warfarin was stopped for 5 days and novel anticoagulants for 2 days pre-procedure. In the hep-bridge cohort, anticoagulants were stopped and were substituted by subcutaneous enoxaparin. The primary outcome was post-polypectomy bleeding. Secondary outcomes included cardiovascular events, all-cause adverse events and emergency department or unscheduled ambulatory office visits within 30 days. The predictive values of the HAS-BLED and CHADS2 scores were evaluated.Results:A total of 662 patients were included, of whom 551 underwent polypectomy (mean age 68.6 years; 97.6% male). Four hundred seventy colonoscopies were performed with no-bridge and 192 with hep-bridge. Post-polypectomy bleeding occurred in 6.0% of procedures: 5.7% in the no-bridge cohort compared to 13.0% of hep-bridge procedures (P=0.0038). Cardiovascular or thrombotic events occurred after 2.6% of the no-bridge and 5.2% of the hep-bridge procedures (P=0.1176). Emergency department or unscheduled office visits within 30 days were reported after 18.7% of the no-bridge procedures and 29.7% of the hep-bridge procedures (P<0.0001). Neither CHADS2 nor HASBLED scores predicted bleeding.Conclusion:The use of hep-bridge was associated with a greater incidence of post-polypectomy bleeding and more emergency department and unscheduled office visits compared with cessation of all anticoagulants.

Post-Anticoagulation Cessation D-Dimer Testing and VTE Recurrence in Real-World Australian Audit

AimElevated D-dimer post-anticoagulation cessation is a recognised risk factor for recurrent venous thromboembolic events (VTE). In particular, raised D-dimer post cessation has been associated with increased risk of recurrence in unprovoked major VTE. Currently in Australia, D-dimer has not been widely used in practice to stratify the risk of VTE recurrence. This study aims to retrospectively analyse the effect of routine D-dimer testing and it's association with VTE recurrence.MethodsA retrospective evaluation was performed on 1024 patients with a diagnosis of VTE at a tertiary hospital in Australia between January 2013 and December 2016. Data collected included demographics, results and timing of D-dimer testing and serial imaging results.Results1024 patients were reviewed with a total median follow up of 12 months (range 0-59 months). D-dimer was tested in 189 patients (18.5%) within 90 days after cessation of anticoagulation. Of these patients, median age was 58 (18-92) and 55.3% (n=105) were female. 33.3% (n=63) had isolated distal deep vein thrombosis (IDDVT), 66.3% (n=126) had above knee DVT (AKDVT)/pulmonary embolus (PE), 54.5% (n=103) of VTE were provoked.Abnormal post cessation D-dimer (>500) was found in 72 patients (37.9%). Of these, 25 patients were restarted on anticoagulation; one had recurrent VTE whilst on low dose apixaban 2.5mg BD and one had recurrence after cessation of anticoagulation at a later date. Patients with elevated D-dimer post cessation had a higher rate of recurrence with the highest risk in patients with D-dimer >1000 (RR 7.38, p=<0.01) outlined in Table 1.Of the 164 patients with post cessation D-dimer testing who remained off anticoagulation there were a total of 24 (12.6%) episodes of recurrent VTE. Elevated D-dimer post anticoagulation cessation was a significant risk factor for recurrence in both provoked VTE (RR 4.21, p=0.01) and unprovoked VTE cohorts (RR 4.55, p=0.008) outlined in Table 2. When provoked VTE were sub-categorised, raised D-dimer demonstrated the most statistical significance in VTE provoked by travel (RR 13.5 p=0.06).Of the patients with post anticoagulation cessation D-dimer testing 170 patients (89.9%) had repeat imaging to assess for residual thrombus. In the subgroup of patients with no residual thrombus, elevated D-dimer was a significant risk factor for VTE recurrence (RR 6.4, p=<0.01). Patients with normal D-dimer and no residual thrombus had the lowest rate of recurrence 5.4% (n=4) see Table 3.When stratified by type of VTE, elevated D-dimer post anticoagulation cessation was significantly related to risk for recurrence in the overall IDDVT sub-cohort (RR 4.09, p=0.007). This was not significant for the AKDVT/PE sub cohort (RR 3.24, p=0.079). However, for patients with unprovoked AKDVT or PE, having D-dimer tested post anticoagulation, regardless of result, was associated with lower rates of VTE recurrence RR 0.30 (p=0.02) compared to those who had no D-dimer testing as part of follow-up.ConclusionPost treatment D-dimer testing may have a clinical role in stratifying the risk of VTE recurrence along with repeat imaging to detect residual thrombus. Elevated D-dimer post anticoagulation cessation is associated with increased risk of VTE recurrence for both provoked and unprovoked VTE with highest risk in patients with D-dimer >1000. Patients with no residual thrombus and a negative D-dimer post anticoagulation cessation had the lowest rate of recurrence. In the subgroup of patients with provoked VTE and IDDVT a positive D-dimer post cessation was associated with 4.21 and 4.09 relative risk of recurrence respectively, suggesting that the role of D-dimer testing can be extended to these subpopulations. Interestingly, in patients with unprovoked AKDVT or PE, having post-cessation D-dimer testing performed, regardless of result, was associated with a significantly lower rate of VTE recurrence compared to patients without D-dimer testing, which may be related to specialist review and recommencement of anticoagulation in high-risk patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Enforcing the 4T: Including a Hard Stop 4T Calculator into the Electronic Medical Record for Heparin Induced Thrombocytopenia

Background: Among many causes of thrombocytopenia acquired during hospitalization, heparin-induced thrombocytopenia (HIT), an immune complex-mediated thrombogenic state with high morbidity and mortality, is one of the most feared etiologies. The clinical ‘4T’ score is an established method to assess risk for HIT and guide immediate management(Lo, Juhl et al. 2006). However, the 4T score is not consistently used by clinicians, leading to potential over-testing and suboptimal management of suspected HIT. Our objective in this Quality Improvement (QI) project was to implement a mandatory 4T calculator (4TC) into the electronic medical record (EMR) to improve the positive predictive value of HIT antibody (HITA) testing, decrease the incidence of testing of low-risk patients, and to improve clinical management of suspected HIT.Methods: We developed a 4TC that assisted clinicians by integrating EMR-derived data on heparin exposure and the five most recent platelet counts with a link to an online calculator as well as clinical suggestions (Figure). As a part of this QI project, clinicians were required to enter the calculated 4T score before ordering a polyspecific HITA assay, which serves as the screening test for HIT in our institution. We reviewed laboratory records for all HITA tests performed over a six-month period, including 3 months before and after the implementation of a “hard stop” for HITA order in the EMR. We extracted data on the ordering hospital service team, 4T score documented in notes (if any), as well as quality of care indicators including rates of clinically recommended heparin cessation and initiation of alternative anticoagulation in the subgroup of patients with intermediate or high 4T score at the time of HITA order. In this QI project, we refrained from any statistical testing and summarized pre-specified outcome measures: incidence of HITA testing, positive predictive value of the HITA assay, and quality of care indicators.Results: We identified 99 (53 prior to the 4TC and 46 post) cases of HITA orders in the study period, among which there were 4 cases of confirmed HIT (either with positive IgG or positive serotonin-release assay [SRA]). Three HIT cases occurred after the 4TC was implemented. After the implementation of the 4TC, the positive predictive value for the HITA assay increased from 9% to 21%. The rate of clinically appropriate heparin order discontinuation increased from 72% to 88%, as did the initiation of alternative anticoagulation from 14% to 27%.HITA assay was most commonly ordered by the internal medicine service (35% of tests), non-cardiac intensive care service (30%), coronary care and cardiothoracic surgery services (21%), neurology (5%), and general surgery/other services (9%). Implementation of the 4TC did not significantly change this distribution, but the overall incidence of HITA orders decreased from 4.0 to 3.4 per 1000 admissions. We observed a high frequency of confirmatory SRA testing requested (18%), which is the reflex confirmatory test performed at our institution, even in cases of negative polyspecific HITA or HIT IgG.Conclusions: Addition of a 4T score calculator into the EMR which provides immediate feedback on patient's prior heparin exposure and recent platelet counts allows clinicians to consistently use the 4T score when considering HIT. Importantly, it also helps to educate non-hematologists on the proper management of HIT. Improved predictive value of the HITA assay suggests that our 4TC led to ordering HITA in a more appropriate patient population. We also demonstrated improved quality of care for suspected HIT, with increased rates of heparin cessation and initiation of alternative anticoagulation in patients with intermediate or high pre-test probability. Identifying clinical teams that order a disproportionate number of HITA assays will help us to direct education to improve clinical management. This QI project has led to other areas of improvement, particularly with regard to rational ordering of the SRA. At only three months of review since implementation of the 4TC, we have noted an improvement in the management of suspected HIT and a slight reduction in the incidence of testing. With continued review, we hope to demonstrate further improvement, as practitioners continue to use the 4TC and rely on clinical rationale rather than reflexive laboratory testing when evaluating thrombocytopenia in the hospital. [Display omitted] DisclosuresOlszewski:TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding; Genentech: Research Funding. Reagan:Alexion: Honoraria; Takeda Oncology: Research Funding; Pfizer: Research Funding.

Fatal recurrent VTE after anticoagulant treatment for unprovoked VTE: a systematic review.

Current guidelines recommend long-term anticoagulant therapy in patients with unprovoked venous thromboembolism (VTE). The risk of fatal recurrent VTE after treatment discontinuation (versus that of fatal bleeding during anticoagulation) is of particular relevance in the decision to continue or stop anticoagulation after the first 3 months. Our primary aim was to provide a point-estimate of the yearly rate of fatal recurrent VTE and VTE case-fatality rate in patients with unprovoked VTE after anticoagulation cessation. Data were extracted from both randomised controlled trials and observational studies published before May 1, 2017. The pooled fatality rates were calculated using a random-effects model. 18 studies with low-to-moderate bias were included in the primary analysis, totalling 6758 patients with a median (range) follow-up duration of 2.2 (1-5) years. After anticoagulation cessation, the weighted pooled rate of VTE recurrence was 6.3 (95% CI 5.4-7.3) per 100 patient-years and the weighted pooled rate of fatal recurrent VTE was 0.17 (95% CI 0.047-0.33) per 100 patient-years, for a case-fatality rate of 2.6% (95% CI 0.86-5.0). These numbers are a solid benchmark for comparison to the risks associated with long-term anticoagulation treatment for the decision on the optimal duration of treatment of patients with unprovoked VTE.

Characteristics, treatment patterns and outcomes of patients presenting with venous thromboembolic events after knee arthroscopy in the RIETE Registry.

Knee arthroscopy is the most common orthopedic procedure worldwide. While incidence of post-arthroscopy venous thromboembolic events (VTE) is low, treatment patterns and patient outcomes have not been described. Patients from the "Registro Informatizado Enfermedad TromboEmbolica" who had confirmed post-arthroscopy VTE were compared to patients with provoked, post bone-fracture, and to patients with unprovoked VTE. Baseline characteristics, presenting signs and symptoms, treatment and outcomes including recurrent VTE, bleeds or death were compared. A total of 101 patients with post-arthroscopy VTE and 19,218 patients with unprovoked VTE were identified. Post-arthroscopy patients were younger (49.5 vs. 66 years, P < 0.0001) and had less history of VTE [5.9% vs. 20%, OR 0.26 (0.11-0.59)]. Among patients with isolated DVT, there were fewer proximal DVT in the post-arthroscopy group [40% vs. 86%, OR 0.11 (0.06-0.19)]. Treatment duration was shorter in the post-arthroscopy group (174 ± 140 vs. 311 ± 340days, P < 0.0001) and more often with DOAC [OR 3.67 (1.95-6.89)]. Recurrent VTE occurred in 6.18 (1.96-14.9) and 11.9 (11.0-12.8) per 100 patient years [HR 0.52 (0.16-1.26)] after treatment in the post-arthroscopy and unprovoked groups, respectively. Recurrent VTE occurred in 5.17 (1.31-14.1) per 100 patient years in a separate post bone-fracture group (n = 147), also not statistically different than the post-arthroscopy recurrence rate. After anticoagulation cessation, some patients post-knee arthroscopy develop VTE. While our small sample size precludes drawing firm conclusions, this signal should warrant further research into the optimal treatment duration for these patients, as some patients may be at increased risk for long-term recurrence.

The cessation of oral anticoagulation following left atrial appendage surgery.

Atrial fibrillation is associated with a significantly increased risk of stroke, and oral anticoagulation is the mainstay of preventative treatment. Scenarios arise where the risks of treatment with oral anticoagulation may outweigh the benefits, most commonly when there is an elevated risk of bleeding. Studies of percutaneous closure of the left atrial appendage have strongly implicated this structure in the etiology of stroke in atrial fibrillation, and provide some rationale for the discontinuation of oral anticoagulation following percutaneous closure device implantation. A common clinical concern is the safety of cessation of oral anticoagulation after surgical closure of the left atrial appendage in patients with a history of atrial fibrillation. Here, we review the evidence guiding this management decision and draw comparison with data on percutaneous closure.

The Use of Bariatric Surgery in Patients with Left Ventricular Assist Devices to Expedite Heart Transplant Candidacy.

Introduction Obesity is a common comorbidity which can complicate management of advance heart failure (AHF) and preclude heart transplant. The use of bariatric surgery has been studied as a weight-loss therapy in AHF patients. The left ventricular assist device (LVAD) has been used as either destination therapy or bridge to candidacy in these obese AHF patients. Methods We reviewed bariatric surgery in LVAD patients who were implanted as bridge to candidacy as a means to expedite candidacy for cardiac transplant. A retrospective chart review was performed on LVAD patients to identify those who underwent bariatric surgery. Clinical data were collected at baseline prior to bariatric surgery and 3 months post-surgery. Data collected included age, etiology of cardiomyopathy, body mass index (BMI), bariatric procedure performed, complications, time to transplant candidacy and ultimate clinical outcome. Three patients (2 female), with a mean age of 51 (range 50-53) were reviewed. All 3 patients had a diagnosis of non-ischemic cardiomyopathy. The average baseline BMI was 39 kg/m2 (range 37- 42). Laparoscopic sleeve gastrectomy was performed on all three patients. Results One patient had significant postoperative bleeding requiring multiple transfusions and reversal of anticoagulation. Anticoagulation was interrupted multiple times during the hospitalization due to bleeding and labile INR levels. A rise in LDH was noted during the hospitalization. One-month post discharge from bariatric surgery the patient was admitted for suspected pump thrombosis with power spikes. She was discharged home after intravenous anticoagulation with baseline LDH and power levels without any neurologic or hemodynamic sequelae. The 3-month average BMI and total weight loss percentage was 34 kg/m2 (range 30 - 38) and 12.5% (range 3.3-20.2%), respectively. All three patients were listed for transplantation with an average time to transplant candidacy of 116 days (range 105-123) following bariatric surgery. Two of the 3 patients received a heart transplant at an average of 145 days (range 130-161) from bariatric surgery. The other patient developed an intracranial hemorrhage 476 days following bariatric surgery and ultimately deemed not a transplant candidate. Conclusion Our retrospective cohort analysis confirms the efficacy of bariatric surgery as a weight loss therapy in obese LVAD patients as a method to shorten time to transplant candidacy. Postoperative bleeding must be managed carefully in consideration of the risk of prolonged cessation of anticoagulation.

Pulmonary embolism four days after interruption of therapy with rivaroxaban

SummaryThrombosis after cessation of anticoagulation, also named rebound thrombosis, is a matter of concern and controversy. There are only few published data about occurrence of rebound thrombosis associated with non-vitamin K-antagonist oral anticoagulant drugs (NOACs). We report on a 58-year-old male with paroxysmal atrial fibrillation (AF) with a CHA2DS2VASC score of 4 who developed central pulmonary embolism four days after interruption of rivaroxaban because of parotid surgery. He had received 40 mg enoxaparin/d. The parotid gland was partially resected within 6 hours without blood loss. Pulmonary embolism and AF occurred on the first postoperative day. He recovered with low-molecular-weight heparin in therapeutic dosages and amiodarone and was discharged with phenprocoumon.The relevance of a rivaroxaban rebound phenomenon, manifesting as arterial embolism, stroke or venous thromboembolism should be clarified. It should be assessed if rebound-phenomena also exist for the NOACs dabigatran, apixaban and edoxaban. Thus, the randomized trials and registries investigating patients with AF or venous thromboembolism should be re-analysed and, based on these data, recommendations should be developed for situations in which NOAC-therapy has to be interrupted or ceased.

Colonic endoscopic mucosal resection in patients taking anticoagulants: Is heparin bridging therapy necessary?

Heparin bridging therapy (HBT) reportedly increases the risk of post-procedural bleeding, and its safety during endoscopic interventions remains unclear. We aimed to evaluate the effects of peri-procedural HBT in patients taking anticoagulants who underwent colonic endoscopic mucosal resection (EMR) for polyps. Patients who underwent colonic EMR while taking a single anticoagulant agent were enrolled in this study. Anticoagulants were temporarily ceased in all patients either without (the non-HBT group, prospectively enrolled) or with HBT (the HBT group, retrospectively enrolled). The incidences of post-procedural bleeding and anemia exacerbation and their length of hospitalization were evaluated and compared. There were altogether 43 consecutive adult patients (30 men; mean age 72.2 ± 7.4 years) in the non-HBT group and 41 sex- and age-matched adults (32 men; mean age 72.9 ± 8.3 years) in the HBT group. There were no significant differences in the location, number or size of resected polyps between the two groups. The percentage of patients with post-procedural bleeding within 2 weeks after colonic EMR in the non-HBT group was lower than that in the HBT group (2.3% vs 9.8%, P = 0.15), although the frequency of anemia exacerbation was not significantly different between the two groups. The total hospitalization length was shorter in the non-HBT compared with the HBT group (4.5 days vs 6.0 days, P < 0.001). No patient in either group developed embolism during hospitalization. Colonic EMR with the temporary cessation of anticoagulants without HBT may be acceptable and beneficial for patients taking anticoagulants.

Optimal time of resuming anticoagulant after endoscopic sphincterotomy in patients at risk for thromboembolism: a retrospective cohort study.

One major adverse event of endoscopic sphincterotomy (EST) is bleeding, which could be more common and severe in patients receiving anticoagulant therapy. However, the cessation of anticoagulants for long periods could lead to thromboembolic events. We aimed to evaluate the optimal timing of resumption of anticoagulants after EST in patients at risk for thromboembolism. From January 2010 through October 2017, a retrospective cohort at risk for thromboembolism who had taken warfarin and bridging therapy with heparin around EST from three tertiary hospitals in South Korea was investigated. The primary outcome was to compare the incidence of post-EST delayed bleeding according to the resumption time of anticoagulant. The secondary outcome was to investigate any thromboembolic adverse events related to interruption of the anticoagulant. A total of 96 patients (46 males and 50 females; median age 75years [range, 24-91years]) were enrolled. Overall, the patient numbers of very early (< 24h), early (24-48h), and late resumption (> 48h) of anticoagulant after EST were 56, 23, and 17, respectively. The baseline characteristics were similar between groups except resumption time of anticoagulant. There was no significant difference in the rate of post-EST delayed bleeding (5% in very early group vs. 9% in early group vs. 0 in late group, p = 0.47). The rate of thromboembolic adverse events was significantly higher in the late resumption of anticoagulant group (0 vs. 0 vs. 24%, p < 0.001). There was no significant difference in the incidence of post-EST delayed bleeding according to the resuming time of anticoagulant. Since long cessation of anticoagulant could increase the risk of thrombotic adverse events, the early resumption of anticoagulant seems to be preferred.

Safety of retrievable inferior vena cava filters in patients with the antiphospholipid syndrome.

Consideration for placement of an inferior cava filter arises in patients with APS where cessation of anticoagulation is necessary or thrombotic complications continue despite maximal anticoagulation. Permanent IVC filters are recommended to be avoided. We evaluated the safety of placement and removal of retrievable inferior vena cava filters in patients with APS. Case series of 5 patients with APS and aPL antibodies who had placement and removal of retrievable IVC filter (because of contraindication to anticoagulation or ongoing thrombosis despite full anticoagulation) to assess for safety, presence of clots in the vena cava or on the filter while in the body, evidence of PE, or clot on the explanted filter. Insertion and removal, even while on anticoagulation, was safe. There was no evidence of clot in the vena cava, on the filter or pulmonary embolism in all cases. Where necessary, retrievable IVC filters may be safer in APS patients but should not be left in for long periods of time.

Effectiveness of adherence to a preoperative antiplatelet and anticoagulation cessation protocol in cardiac surgery.

Reduction of blood loss after cardiac surgery remains challenging. The effectiveness of adherence to a protocol on cessation of anticoagulants and platelet-inhibiting medications was investigated together with the influence of protocol violations on blood loss after surgery, use of blood products, surgical re-explorations and 30-day mortality. Between 2009 and 2013, data were collected prospectively for all elective cardiac surgery procedures in adult patients (n = 1637). Two groups were distinguished: Group 1 adhered to the protocol for cessation or continuation of medication (n = 1287, 79%) and Group 2 violated the protocol (n = 350, 21%). Median blood loss was 300 ml (interquartile range 175-500 ml). Eighty patients underwent re-exploration due to blood loss (5%). Thirty-day mortality was 2% (n = 27). Protocol violation was associated with increased blood loss [median 275 ml (175-475 ml) vs 350 ml (250-612); P ≤ 0.001] and with increased average use of fresh frozen plasma (226 ml vs 139 ml; P << 0.00001), red blood cell transfusion (115 ml vs 87 ml; P = 0.081) and thrombocyte transfusions (52 ml vs 37 ml; P = 0.0082). The number of re-explorations (4% vs 6%; P = 0.39) and mortality risk (1% vs 2%; P = 0.72) did not differ. Balancing the benefit of continuing platelet inhibitors or anticoagulants versus cessation before surgery remains challenging. Adherence to the protocol will lead to lower blood loss and in a lower consumption of blood products although the decision to go for re-exploration and 30-day mortality does not differ compared with the protocol violation. Stopping medication does not lead to thromboembolic events.

Arnica and Bromelain for Blepharoplasty-Associated Ecchymosis

Homeopathic and naturopathic supplementation has gained increasing popularity as complementary and alternative medicine (CAM) modalities. Arnica and Bromelain are 2 commonly used supplements thought to be effective in reducing ecchymosis. This study was designed to explore the impact of combination therapy with Arnica and Bromelain on postoperative ecchymosis in patients undergoing blepharoplasty. In total, 130 patients undergoing upper eyelid blepharoplasty were enrolled. Patients with bleeding diatheses or inability to comply with cessation of anticoagulants were excluded. Aspirin and all naturopathic and homeopathic treatments were discontinued 2 weeks prior to surgery. In all, 64 patients received oral Arnica and Bromelain treatment starting 7 days prior to surgery and extending 7 days postoperatively. Sixty-six patients received no supplementation. Upper eyelid blepharoplasty was performed with skin flap excision, hemostasis with electrocautery, and closure with running 6-0 fast absorbing plain gut. Postoperative photos were taken 7 days following surgery. Photos were analyzed by 2 blinded reviewers, who graded the severity of ecchymosis using a visual analog scale. All 130 patients were seen during the postoperative course. There were no patients lost to follow-up, and there were no adverse reactions to the treatment protocol that necessitated discontinuation of Arnica and Bromelain. Average ecchymosis in the treatment arm was 5.00 compared with 4.43 in the control arm ( P = .67). At the conclusion of this study, the investigators find insufficient evidence that the combination of Arnica and Bromelain is effective at producing a statistically significant difference in ecchymosis following upper eyelid blepharoplasty.

Anticoagulation strategies in patients with deep vein thrombosis and pulmonary artery embolisms

Deep vein thrombosis and pulmonary artery embolisms share pathophysiological features and are therefore collectively referred to as venous thromboembolisms (VTE). While the incidence of VTE has been increasing for years as aresult of demographic changes and improved diagnostics, the morbidity and mortality are decreasing. This is particularly due to more sensitive diagnostics, improvements in risk stratification and more effective anticoagulation strategies. The aim of effective anticoagulation therapy is the avoidance of early events up to death and prevention of recurrent events. Anticoagulation treatment should be started with either heparins (unfractionated or low molecular weight), the pentasaccharide fondaparinux or direct oral anticoagulants. Patients with recurrent events qualify for indefinite anticoagulation treatment. For afirst episode of VTE anticoagulation treatment for at least 3months is recommended (maintenance therapy). Subsequently, prolonged maintenance therapy for secondary prevention can be meaningful, depending on the individual patient risk (provoked event, risk for recurrence or bleeding). The non-vitamin K antagonist oral anticoagulants (NOACs) have now also been approved for this indication. As aresult of a probably permanently high risk for recurrent events of up to 10% per year after cessation of anticoagulation, insufficient scores for estimation of the risk of bleeding and recent data documenting the safety and efficacy of NOACs for secondary prevention, ashift towards prolonged anticoagulation of 3-6months or even indefinite (>1 year) treatment can be anticipated for patients after thromboembolic diseases.

The Impact of Electrical Calf Muscle Stimulation on the Residual Venous Obstruction and DVT Recurrence after Cessation of Standard Anticoagulation

Aim. To assess the efficacy of electrical calf muscle stimulation (EMS) in patients with post-thrombotic syndrome (PTS) and residual venous obstruction (RVO) after cessation of a standard anticoagulation.Methods. This was a prospective comparative clinical trial with masked outcome assessor involving patients after the first episode of unprovoked femoro-popliteal DVT who have completed a standard 6-month course of anticoagulation and had signs of RVO in the affected veins and Villalta score of 5 and more.Totally were enrolled 60 patients in the age of 40-86 years (mean - 58,5 ± 11,4), 38 men and 22 women, divided into two groups of 30 participants. In both groups (main and control) PTS was treated by active walking (at least 5,000 steps per day controlled by an individual pedometer), below-knee graduated compression stockings (23-32 mm Hg) and micronized purified flavonoid fraction (2-month course twice a year). In the main group, EMS with «Veinoplus VI» device (3 procedures of 30 minutes every day) also was used. The main endpoint of the study was symptomatic or asymptomatic recurrent venous thrombosis confirmed by duplex ultrasound (DUS). The additional criteria of treatment efficacy were changes in the degree of current venous stenosis. The patients were followed up for 12 months with monthly DUS, aimed to reveal recurrent DVT, and 6-monthly DUS with evaluation of stenosis degree.Results. RVO was represented by an average of 48%-stenosis of the common femoral vein in 12 patients, 53%-stenosis of the superficial femoral vein in 16 cases and 55%-stenosis of the popliteal vein in all participants. Through 12-month follow up the degree of stenosis decreased in all affected veins in both groups (p<0,05). The most vivid dynamics was found in the popliteal vein: 60.8% - 55.1% - 28.8% in the main group and 50.9% - 30.1% - 27.3% in the control group (p<0,0001) with significant differences between the groups (p=0.004)Recurrence of venous thrombosis was found in 7 of 30 patients in the control group and in 0 of 30 patients in the main group (23.3% vs 0%, p=0.011). In 5 cases the recurrent DVT was silent and revealed by regular DUS and only in 2 cases it had a clinical manifestation. 4 of 5 silent cases were presented with re-occlusion of the early affected vein.Conclusions. There is an ongoing process of deep veins recanalization during 12 months after cessation of anticoagulation in patients with RVO and PTS. Using of EMS in complex treatment of PTS allows to reduce the rate of recurrent DVT and increase the speed of recanalization. DisclosuresLobastov:“Gemakor Labs” Ltd: Honoraria, Research Funding; “BEHO+” Ltd: Honoraria, Research Funding. Ryzhkin:“BEHO+” Ltd: Research Funding. Laberko:“Gemakor Labs” Ltd: Honoraria, Research Funding; “BEHO+” Ltd: Honoraria. Rodoman:“Gemakor Labs” Ltd: Research Funding.