Bridging Anticoagulation Research Articles

Early Anticoagulation Bridging to Therapeutic International Normalized Ratio after Left Ventricular Assist Device Implantation is Not Associated with Thromboembolic and Bleeding Complications: A Systematic Review and Meta-Analysis

Purpose Thromboembolism (TE) is common after left ventricular assist device (LVAD) implantation and early anticoagulation (AC) bridging to therapeutic international normalized ratio (INR) has been widely implemented to prevent this complication. However, some studies suggested that no early AC bridging after LVAD implantation decreases bleeding complications without increase in incidence of TE. This meta-analysis aimed to evaluate the association between early AC bridging after LVAD implantation and incidence of TE and bleeding complications. Methods We performed a comprehensive literature search through September 2018 using MEDLINE and EMBASE. Included studies were prospective or retrospective cohort studies that compared the incidence of TE and bleeding in LVAD patients with and without early AC bridging to therapeutic INR. We calculated pooled odds ratio (OR) with 95% confidence intervals (CI) and I2 statistic using the random-effects model. Results Six studies were included in this meta-analysis. All patients had continuous-flow LVADs implanted. TE events were reported in 6 studies involving 897 patients (611 with bridging, 286 without bridging). Bleeding complications were reported in 4 studies involving 623 patients (405 with bridging, 218 without bridging). Median follow-up was 3.5 months. There was no association between AC bridging and incidence of TE (RR: 0.68; 95% CI: 0.41-1.12, I2=0%) and bleeding complications (RR: 0.98; 95% CI: 0.61-1.57, I2=32%) (Figure). Conclusion Our meta-analysis suggests that early AC bridging to therapeutic INR after LVAD implantation is not associated with decreased TE and increased bleeding complications. Controlled trials are warranted to further investigate the utility of early AC bridging after LVAD implantation in patients at high risk for TE complications.

Evaluation of Outpatient Anticoagulation Bridging after Left Ventricular Assist Device (LVAD) Implantation

Purpose The LVAD is a mechanical circulatory support device that provides hemodynamic support to patients with heart failure. An antithrombotic regimen including warfarin (target international normalized ratio [INR] 2.0-3.0) and aspirin is standard of care following LVAD implantation. The aim of this study is to evaluate the safety of outpatient anticoagulation bridging in the setting of a subtherapeutic INR following LVAD implantation. Methods This study is a retrospective, single-center cohort of adult patients who underwent LVAD implantation (HeartMate II™ or HeartMate 3™). Patients receiving warfarin and at least one dose of therapeutic enoxaparin or fondaparinux for anticoagulation bridging in the outpatient setting between September 1, 2015 and June 30, 2018 were included. The primary endpoint was the incidence of bleeding complications within 1 week of completing the bridging episode. Secondary endpoints included the incidence of new hemolysis or thrombotic events within 30 days, INR at the time of bridge initiation, duration of anticoagulation bridge, and management of bleeding events associated with the bridging episode. Results Data from 160 bridging episodes in 44 patients were analyzed. The majority of patients had implantation of a HeartMate II™ LVAD (93.2%). Enoxaparin was the predominant bridging anticoagulant (97.7%). The primary endpoint occurred during 25 encounters (15.6%) in 14 patients. Of these events, 11 systemic bleeding episodes (6.9%) occurred. Local bleeding complications included injection site bleeding (1.9%), bruising (6.3%), and hematomas (0.6%). The majority of bleeding episodes (81.0%) were self-managed by the patient or with monitoring [INR or bleeding] only. Data analysis of new hemolysis, stroke, and/or thrombosis within 30 days of any bridging episode is ongoing. The mean pre- and post-bridge INRs were 1.63 and 2.58, respectively. The average duration of a bridging episode was 4.6 days (median 3.8). Conclusion Outpatient anticoagulation bridging following LVAD implantation was associated with a modest risk of bleeding complications. The majority of bleeding episodes were localized events treated with self-management only. Results of this study may suggest an overall benefit of bridging during periods of subtherapeutic warfarin therapy following LVAD implantation, pending further data analysis.

MANAGEMENT OF ANTICOAGULATION IN PATIENTS WITH STROKE AND VALVULAR ATRIAL FIBRILLATION BEFORE SCREENING COLONOSCOPY: IS BRIDGING THERAPY ALWAYS NECESSARY?

The periendoscopic management of anticoagulation (AC) in patients with valvular atrial fibrillation and history of embolic stroke is an area of uncertainty. Despite the availability of some guideline recommendations, the decision regarding bridging AC is usually at the discretion of the physician.

Impact of drugs on venous thromboembolism risk in surgical patients.

This review focuses on the most common drugs administered to surgical patients during the perioperative period that affect the risk of venous thromboembolism (VTE). Among analgesics, the risk of VTE is increased in patients treated with diclofenac, ibuprofen, and rofecoxib, but not naproxen, while metamizole can confer a protective effect. The relationship between sedatives and VTE has not been sufficiently studied. Tricyclic antidepressants, low-potency serotonin reuptake inhibitors, and antipsychotics have been associated with increased risk of VTE. The use of diuretics in the perioperative period is poorly researched; however, hyponatremia is considered a risk factor. Other factors that may influence the risk of VTE include bridging anticoagulation, allogeneic transfusion, and hemostatic management before surgery. Pharmacotherapy for HIV or cancer may also increase VTE risk. Increased monitoring for VTE is therefore advisable in surgical patients and those receiving antipsychotics, antidepressants, diuretics, or analgesics.

Abstract TP379: Antithrombotic Bridging in Patients With Acute Ischemic Stroke and Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a prevalence of 5.9% in those over age 65. AF increases stroke risk 5-fold, causing 1 in 6 acute ischemic strokes (AIS). Stroke from AF carries a higher early mortality and poorer functional outcome, and a risk of recurrent AIS, when compared to ischemic stroke patients in sinus rhythm, of approximately 5% in the first 2-4 weeks. The CHADS2 score is used to estimate stroke risk of non-valvular AF. Anticoagulation is recommended for a score of > 2 unless contraindicated. Controversy exists regarding whether AF patients with AIS should receive parenteral anticoagulation or antiplatelet therapy as a bridging method to oral anticoagulation. Methods: We conducted a single center retrospective chart review of patients admitted between 6/2011 and 3/2014, with diagnosis of AIS and AF (n=354), as part of quality improvement. Bleeding complications related to bridging therapy and incidence of recurrent stroke were reviewed. Results: Complications were seen in 24 (13.3%) patients receiving parenteral bridging anticoagulation (n=180, 50.8%), including 14 intracranial and 14 extracranial bleeding events (7.7% each). Multiple bleeding complications were seen in 2.2% (n=4). Bleeding complications were seen in 5.5% (n=9) of patients receiving antiplatelet bridging (n=161, 45.4%), with 4.3% intracranial (n=7) and 1.2% extracranial (n=2) bleeding events. None had more than one bleeding complication. Relative risk for bleeding complications with parenteral anticoagulation versus antiplatelet bridging was 2.38 (CI 1.1426 to 4.9793, p=0.02). Thirteen patients (3.6%) received no bridging and had no bleeding complications. Two patients of 354 (0.5%) had recurrent ischemic events, one each in the parenteral anticoagulation and antiplatelet groups. Conclusions: Preliminary data does not support bridging with parenteral anticoagulation in AIS and AF due to higher incidence of bleeding complications and low incidence of recurrent AIS. These findings may be related to the limited number of patients included in this study. A future goal is to increase the number of patients reviewed to strengthen the validity of these results.

Anticoagulation in CKD and ESRD.

In this review we discuss the evolving literature of anticoagulation in the context of the nephrology patient. Whereas CKD patients with atrial fibrillation, should be anticoagulated, the benefit of anticoagulation for those on dialysis remains controversial due to an increased risk of bleeding. The availability of direct oral anticoagulants offers new options for those with CKD. Until studies are available in stage 4 and 5/dialysis, this class of medication should be used with caution in this population. For anticoagulated patients requiring interventional procedures, a risk-based approach should be employed to determine those who will benefit from bridging anticoagulation. Either unfractionated heparin or low molecular weight heparin are adequate choices for bridging anticoagulation. Unfractionated heparin and renally dosed low molecular weight heparin can be safely used in non-end stage CKD patients with an acute coronary syndrome. Similarly, the use of unfractionated heparin and low molecular weight heparin are comparable for thromboembolic prophylaxis in CKD/dialysis and extracorporeal circuit anticoagulation of the dialysis circuit.

Perioperative bridging of vitamin K antagonist treatment in patients with atrial fibrillation: only a very small group of patients benefits.

Bridging anticoagulation in atrial fibrillation (AF) patients who need to interrupt vitamin K antagonists for procedures is a clinical dilemma. Currently, guidelines recommend clinicians to take the stroke and bleeding risk into consideration, but no clear thresholds are advised. To aid clinical decision making, we aimed to develop a model in which periprocedural bridging therapy is compared with withholding anticoagulation in AF patients, for several bleeding and stroke risk groups. A model was developed to simulate both a bridge and a non-bridge cohort, using simulated international normalized ratio (INR) values for patients on warfarin, acenocoumarol, and phenprocoumon. For both clinical strategies, stroke and bleeding risks were included and outcomes were stratified by CHA2DS2-VASc or CHADS2 and HAS-BLED groups. Quality-adjusted life expectancy was the main outcome considered. Our analyses show bridging to only be beneficial for patients with HAS-BLED scores equal or lower to 2 and with CHA2DS2-VASc scores of 6 or higher. For patients using acenocoumarol bridging may be beneficial starting at a CHA2DS2-VASc score of 7. Post-procedural time to therapeutic INR has a significant influence on the results: no significant benefit of bridging was found for patients reaching therapeutic INR values within 5 days. When deciding whether to bridge anticoagulation, clinicians should consider the patient's individual stroke and bleeding risk, while also considering the patient's post-procedural INR management. In practice, only a small subset of patients is expected to benefit from bridging anticoagulation treatment.

Cost-Effectiveness of Bridging Anticoagulation Among Patients with Nonvalvular Atrial Fibrillation.

Bridging anticoagulation is commonly prescribed to patients with atrial fibrillation during initiation and interruption of warfarin. Guidelines recommend bridging patients at high risk of stroke, while a recent randomized trial demonstrated overall harm in a population at comparatively low risk of ischemic stroke. Theory suggests that patients at high risk of stroke and low risk of hemorrhage may benefit from bridging, but data informing patient selection are scant. To estimate the utility and cost-effectiveness of bridging anticoagulation among patients with nonvalvular atrial fibrillation, stratified by thromboembolic and hemorrhagic risk DESIGN: Cost-effectiveness analysis with lifelong time horizon, from the perspective of a third-party payer MAIN MEASURES: Quality-adjusted life years (QALYs) per bridged patient; US dollars per QALY gained KEY RESULTS: Unselected patients with nonvalvular atrial fibrillation may be harmed by bridging anticoagulation. Hospital admission for bridging is almost never cost-effective, and generally harmful. Among patients carefully selected by both thromboembolic and hemorrhagic risks, outpatient bridging can be beneficial and cost-effective. Results were sensitive to how effectively heparin products reduce stroke risk. Outpatient bridging anticoagulation can be beneficial and cost-effective for a subset of patients with nonvalvular atrial fibrillation during interruption or initiation of warfarin. Admission for bridging should be avoided.

Anticoagulant Bridge Comparison in Mechanical Circulatory Support Patients.

Maintaining mechanical circulatory support (MCS) device patients in a specified therapeutic range for anticoagulation remains challenging. Subtherapeutic international normalized ratios (INRs) occur frequently while on warfarin therapy. An effective anticoagulant bridge strategy may improve the care of these patients. This retrospective review of MCS patients with subtherapeutic INRs compared an intravenous unfractionated heparin (UFH) strategy with a subcutaneous enoxaparin or fondaparinux strategy. Native thromboelastography (n-TEG) was used to evaluate anticoagulant effect with coagulation index (CI) as the primary outcome measure. Enoxaparin 0.5 mg/kg subcutaneously (SC) every 12 hours or fondaparinux 2.5-5 mg SC daily were compared with an initial UFH rate of 5 units/kg/hr and titrated to stated n-TEG goal range. The anticoagulant groups UFH, enoxaparin, and fondaparinux were found to be statistically similar with regard to frequency in n-TEG goal range, above range (hypercoagulability), or below range (hypocoagulability). Clinical outcomes were similar among groups with three gastrointestinal bleeds in UFH, one in enoxaparin, and one in fondaparinux groups. Device thrombosis occurred in one UFH patient, while UFH and fondaparinux groups had one ischemic cerebrovascular accident event each. These strategies provided comparable n-TEG results and clinical outcomes when compared with intravenous UFH. Low-dose enoxaparin or fondaparinux may provide an alternative anticoagulant bridging option in MCS patients presenting with subtherapeutic INR.

Patients Prescribed Direct-Acting Oral Anticoagulants Have Low Risk of Postpolypectomy Complications

Use of direct-acting oral anticoagulants (DOACs) is increasing, but little is known about the associated risks in patients undergoing colonoscopy with polypectomy. We aimed to determine the risk of post-polypectomy complications in patients prescribed DOACs. We performed a retrospective analysis using Optum's de-identified Clinformatics Data Mart Database (2003-2016) (a de-identified administrative database from a large national insurance provider) to identify adults who underwent colonoscopy with polypectomy or endoscopic mucosal resection (EMR) from January 1, 2011, through December 31, 2015. We collected data from 11,504 patients prescribed antithrombotic agents (1590 DOAC, 3471 warfarin, and 6443 clopidogrel) and 599,983 patients not prescribed antithrombotics of interest (controls). We compared 30-day post-polypectomy complications, including gastrointestinal bleeding (GIB), cerebrovascular accident (CVA), myocardial infarction (MI), and hospital admissions, of patients prescribed DOACs, warfarin, or clopidogrel vs controls. Post-polypectomy complications were uncommon but occurred in a significantly higher proportion of patients receiving any antithrombotic vs controls (P < .001). The percentage of patients in the DOAC group with GIB was 0.63% (95% CI, 0.3%-1.2%) vs 0.2% (95% CI, 0.2%-0.3%) in controls. The percentage of patients with CVA in the DOAC group was 0.06% (95% CI, 0.01%-0.35%) vs 0.04% (95% CI, 0.04%-0.05%) in controls. After we adjusted for bridge anticoagulation, EMR, Charlson comorbidity index (CCI), and CHADS2 (congestive heart failure, hypertension, age over 75, diabetes, stroke [double weight]) score, patients prescribed DOACs no longer had a statistically significant increase in the odds of GIB (odds ratio [OR], 0.90; 95% CI, 0.44-1.85), CVA (OR, 0.45; 95% CI, 0.06-3.28), MI (OR, 1.07; 95% CI, 0.14-7.72), or hospital admission (OR, 0.86; 95% CI, 0.64-1.16). Clopidogrel, warfarin, bridge anticoagulation, higher CHADS2, CCI, and EMR were associated with increased odds of complications. In our retrospective analysis of a large national dataset, we found that patients prescribed DOACs did not have significantly increased adjusted odds of post-polypectomy GIB, MI, CVA, or hospital admission. Bridge anticoagulation, higher CHADS2 score, CCI, and EMR were risk factors for GIB, MI, CVA, and hospital admissions. Studies are needed to determine the optimal peri-procedural dose for high-risk patients.

Periprocedural Interruption of Anticoagulation in Patients with Cancer-Associated VTE: An Analysis of Thrombotic and Bleeding Outcomes

Background: Approximately 10-20% of patients with venous thromboembolic events (VTE) have underlying malignancy. VTE is considered the second leading cause of death in patients with cancer, and patients with cancer-associated VTE are at higher risk of anticoagulant-related bleeding. Although patients with cancer often undergo diagnostic or therapeutic invasive procedures, there is a paucity of data on adverse outcomes following the periprocedural interruption of anticoagulation in this patient population.Methods: We did a single-center, retrospective chart review of consecutive patients with cancer-associated VTE who had periprocedural interruption of anticoagulation for invasive procedures between November 2015 and March 2018. Perioperative interruption of warfarin/low-molecular-weight heparin was done as per CHEST guidelines (Douketis et al. Chest 141(2 Suppl). Heparin bridging anticoagulation was used only for patients with recent (< 3 months) VTE. Perioperative interruption of direct oral anticoagulants (DOACs) was done as per Thrombosis Canada guidelines, with anticoagulation held for 3 half-lives prior to low bleeding risk procedures and 5 half-lives for high bleeding risk procedures. Active cancer was defined as per the HOKUSAI VTE CANCER trial (Raskob et al. NEJM 378(7)). Primary outcomes were 30-day post-operative rates of VTE and major bleeding. Secondary outcomes were 30-day post-operative rates of clinically relevant non-major bleeding (CRNMB) and mortality. Major bleeding and CRNMB were defined according to ISTH definitions. Data are reported on a per-interruption basis. Herein, we present an interim analysis of results.Results: To date, 82 perioperative interruptions are included, of whom 69.5% were receiving a DOAC. Mean age of the cohort was 65.8 years, 62.2% were male, 92.6% had active cancer and 41.5% had metastatic cancer. Thrombocytopenia (platelet count < 100 x 106/L) was present in 12.2% of interruptions. Procedures were stratified as high bleeding risk in 65.9% of cases. The 30-day rates of thromboembolism and major bleeding were both 3.70 % (95% confidence interval [CI] 1.25 to 10.2%), as was the 30-day rate of CRNMB. There were no deaths during the 30-day follow-up period.Conclusions: The periprocedural interruption of anticoagulation in patients with cancer-associated VTE appears to be associated with high rates of post-operative thrombotic and bleeding complications. Prospective studies are required to better quantify the risks of periprocedural anticoagulation interruption in this patient population. DisclosuresShaw:Portola Pharmaceuticals: Research Funding. Douketis:BMS: Other: Advisory Board; Janssen: Consultancy; Bayer: Other: Advisory Board; Pfizer: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Portola: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; Biotie: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; The Medicines Company: Other: Advisory Board. Carrier:Pfizer: Honoraria; Bayer: Honoraria; BMS: Honoraria, Research Funding; Leo Pharma: Research Funding.

Double Blind Randomized Control Trial of Postoperative Low Molecular Weight Heparin Bridging Therapy for Patients Who Are at High Risk for Arterial Thromboembolism (PERIOP 2)

▪BackgroundIt remains uncertain if patients with atrial fibrillation or mechanical heart valves requiring interruption of warfarin for procedures benefit from post-procedure anticoagulant bridging therapy.MethodsIn order to determine the efficacy and safety of postoperative LMWH bridging, we conducted a multicenter randomized double-blind controlled trial of patients with atrial fibrillation or a mechanical heart valve who require interruption of warfarin for a planned procedure. We excluded patients with active bleeding within 30 days, platelet count <100 x10⁹/L, spinal, cardiac or neurosurgery, life expectancy <3months, creatinine clearance <30ml/min, multiple mechanical valves or a Starr-Edwards valve, mechanical valve with history of stroke or TIA, or a history of heparin induced thrombocytopenia. The last dose of warfarin was given 6 days prior to the procedure. All patients received pre-procedure bridging therapy with dalteparin 200 IU per kilogram (max 18,000 IU) subcutaneously in the morning day-3 and day-2 then dalteparin 100 IU per kilogram (max 18,000 IU) subcutaneously 24 hours pre-procedure. Warfarin was resumed in the evening of the procedure at twice the usual dose for the first two days and then titrated according to INR. After the procedure (same day or next day), when hemostasis had been achieved, patients were randomized to receive dalteparin or placebo for at least 4 days and until the INR was greater than 1.9. Randomization was stratified by presence of a mechanical valve, by the post-procedure risk for major bleeding, and by centre. For patients at high risk for post-procedure major bleeding, dalteparin or placebo was administered at a fixed daily dose of 5000 IU. For patients at low risk for post-procedure major bleeding, dalteparin or placebo was administered at a daily dose of 200 IU per kilogram (max 18,000 IU). The primary analysis was a comparison of the proportion of patients who had major thromboembolism (stroke, proximal DVT, PE, MI, peripheral embolism) over 90 days by Chi-squared test according to the intention to treat principle. Secondary outcomes were major bleeding, all cause mortality and a composite outcome of major thromboembolism and major bleeding.ResultsStarting in October 2006 we randomized a total of 1471 patients of whom 1167 had atrial fibrillation (without mechanical heart valves) and 304 had mechanical valves (99 also had atrial fibrillation). Last follow up was completed in May 2016. Baseline characteristics were similar between the LMWH and the placebo groups (see Table 1). Due to a randomization program system error at two centres more atrial fibrillation patients were randomized to dalteparin rather than to placebo. Major thromboembolism occurred in 6/820 (0.71%) dalteparin patients and 7/650 (1.11%) placebo patients. Major post-procedure bleeding occurred in 12 (1.46%) dalteparin patients and 16 (2.46%) placebo patients. Findings were similar in patients with atrial fibrillation alone and in patients with mechanical heart valves (with or without atrial fibrillation) (Table 2).ConclusionsIn patients with atrial fibrillation and/or mechanical heart valves who had warfarin interrupted for a procedure there was no benefit from post-procedure LMWH bridging. [Display omitted] DisclosuresKovacs:Bayer: Research Funding; Daiichi Sankyo Pharma Development: Research Funding. Wells:Janssen: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Bayer: Honoraria. Schulman:Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria.

Web Exclusive. Annals for Hospitalists Inpatient Notes - How I Changed My Practice-Perioperative Bridging Anticoagulation.

Perioperative management of patients receiving systemic anticoagulation for atrial fibrillation or flutter can be challenging. This commentary discusses why clinicians should reconsider the need to...

Erratum: Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice.

In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64–0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71–0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70–0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.

Postoperative bridging anticoagulation and left ventricular assist system thrombosis.

Reduced emphasis on early postoperative bridging anticoagulation is one explanation for the increased incidence of HeartMate II (HM II) pump thrombosis. We conducted a single-center analysis of initial postoperative anticoagulation practices and their impact on the incidence of HM II pump thrombosis. Data was collected on 105 patients undergoing primary HM II implant from 2009 to 2014. A parenteral bridge was defined as use of parenteral anticoagulation prior to attainment of an international normalized ratio ≥ 2 on warfarin. A parenteral bridge was further characterized as early if initiated ≤ 3 days of implant and therapeutic if a manufacturer-specified goal partial thromboplastin time (PTT) was achieved during each of the first 3 days of administration. Pump thrombosis was "suspected" based upon suggestive clinical parameters leading to hospital admission with parenteral anticoagulant administration and "confirmed" by direct visualization of thrombus in the device. A majority of patients (70%) were treated with an initial parenteral bridge, which was started within 3 days of device implantation in 68% of cases. Therapeutic PTT levels were achieved in 52% of patients treated with a parenteral bridge. Patients who were bridged had lower Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles (p = 0.039) and longer intensive care unit stay (p = 0.005). Pump thrombosis was suspected in 25% and confirmed in 13% of patients within 6 months of implant. Point estimates of pump thrombosis incidence demonstrated a lower event rate at 6 months in patients who received a therapeutic bridge (15.8%, 95% CI 6.3-29.1% for suspected; 7.9%, 95% CI 2.0-19.3% for confirmed) compared to those who did not receive a therapeutic bridge (29.9%, CI 19.3-41.1% for suspected; 16.4%, 95% CI 8.7-26.3% for confirmed). This trend was not sustained at 12 and 24 months. Cumulative incidence analyses showed no significant difference in the overall incidence of pump thrombosis between patients who did and did not receive a parenteral bridge. In patients undergoing HM II implantation, the use of initial postoperative parenteral bridging anticoagulation is common but frequently sub-therapeutic. Use of a parenteral bridge reaching therapeutic targets may decrease the 6-month but not the overall incidence of pump thrombosis.

Survey of the management of perioperative bridging of anticoagulation and antiplatelet therapy in neurosurgery.

A growing number of patients on anticoagulation or antiplatelet therapy (APT) are planned for elective surgery. The management of perioperative anticoagulation and APT is challenging because it must balance the risk of thromboembolism and bleeding, and specific recommendations for the management of bridging in neurosurgical patients are lacking. We surveyed German neurosurgical centers about their management of perioperative bridging of anticoagulation and APT to provide an overview of the current bridging policy. From April to August 2016, all German neurosurgical departments were invited to participate in the survey. We used SurveyMonkey to compose ten questions and to conduct the survey, and we defined three different approaches for the perioperative management of patients on a preexisting medication: medication will be discontinued (A) with perioperative "bridging" and (B) without perioperative bridging, or (C) medication will be continued perioperatively. Out of 141 respondents, 84 (60%) partially and 77 (55%) fully completed the questionnaire. No defined policy for the perioperative management of anticoagulation and APT was established in 60.7% (51/84) of participating centers. The perioperative management of anticoagulation and APT varied widely among different centers in all items of the questionnaire; for example, in the group of patients at high risk for thromboembolism, acetylsalicylic acid was discontinued in 22%, bridged in 35%, and continued in 35% of centers. There is significant uncertainty regarding the management of perioperative bridging of anticoagulation and APT in neurosurgery because of a lack of prospective and limited retrospective data.

Management of dental extractions in patients on warfarin and antiplatelet therapy.

Planning dental extractions for Taiwanese patients on antithrombotic therapy remains controversial. This study aimed to examine management of dental extraction in patients on warfarin and antiplatelet therapy. Subjects comprised 1331 patients, with (1) 60 on warfarin with intentional normalized ratio (INR) below 4.0 (warfarin continued: 28 patients/33 occasions; warfarin stopped and switched to heparin under hospitalization: 32 patients/37 occasions); (2) 183 on antiplatelet therapy (aspirin: 125 patients/185 occasions; clopidogrel: 42 patients/65 occasions; dual therapy: 16 patients/24 occasions); and (3) a control group of 1088 patients/1472 occasions without any antithrombotic therapy. The patient's clinico-demographic parameters, warfarin effectiveness (dose and INR levels) and antiplatelet therapy, number and type of dental extraction and incidence of postoperative bleeding were investigated. Incidence of postoperative bleeding in the warfarinized group (warfarin continued: 9.1%; warfarin stopped: 8.1%) was higher than in the antiplatelet group (aspirin: 1.1%; clopidogrel: 3.1%; dual antiplatelet: 4.2%), and the control group (0.7%), but these differences were not significant and unrelated to INR or number and type of dental extraction. Postoperative hemorrhage was managed successfully by repacking with Gelfoam impregnated with tranexamic acid powder in most patients. The study indicated that there is no need to interrupt warfarin (INR<4.0) and antiplatelet therapy before dental extractions in Taiwanese patients. A sufficient hemostasis could be obtained using local measures. This approach can save these individuals from becoming exposed to the risk of thromboembolism and the inconvenience of bridging anticoagulation with heparin.

Bridging anticoagulation in patients treated with vitamin K antagonists prior to trochanteric and hip fracture surgeries: The current practice.

The strategies of perioperative bridging anticoagulation in orthopedic surgical patients during oral anticoagulation (OAC) therapy with vitamin K antagonists (VKA) vary from center to center. The aim of this single-center study was to assess the risk of bleeding and thromboembolic events (TEs) in bridged patients on VKA who underwent orthopedic surgery due to trochanteric or hip fracture. The retrospective study included 64 patients (mean age: 80 years) who received VKA for at least 3 months prior to orthopedic procedure. All subjects were bridged with enoxaparin (40 mg once a day). The control group (n = 69) comprised of age-, sexand procedure-matched patients operated on for the same indications, but with neither a history of VKA therapy nor perioperative bridging anticoagulation. Severe postoperative bleeding occurred in 19 (29.7%) patients from the VKA group and in 13 (18.8%) controls (p = 0.16). Within the VKA group, intertrochanteric fractures (52.6%) and femoral neck fractures (47.4%) occurred more often in patients with bleeding than other lower extremity fractures (0%; p = 0.03). Severe adverse events (SAEs) were more common in the VKA group than in the controls (12.5% vs 1.5%; p = 0.01). Patients from the VKA group did not differ from the controls in the incidence of TEs (6.3% vs 8.9%; p = 0.31). No intrahospital mortality was documented. Prophylactic administration of enoxaparin is a common strategy of bridging anticoagulation in a hospital setting. This approach does not seem to be associated with an increase in thromboembolic risk nor higher risk of bleeding in orthopedic patients who received VKA preoperatively.

Safety and Efficacy of Routine Bridging Anticoagulation for Subtherapeutic Anticoagulation in Outpatients with a Left Ventricular Assist Device

Background&#x0D; Anticoagulation with vitamin K antagonists is vital to prevent pump thrombosis in patients with left ventricular assist devices (LVADs). However, the safety and efficacy of bridging anticoagulation for the routine management of subtherapeutic international normalized ratio (INR) in stable outpatients remains poorly characterized.&#x0D; Methods &#x0D; In this retrospective study, a total of 60 LVAD outpatients had 110 episodes of subtherapeutic INR noted on routine testing. 34 of these episodes were managed with parenteral bridging anticoagulation and 76 were managed with only an adjusted dose of warfarin. The rates of bleeding and thromboembolic adverse events following these episodes of subtherapeutic INR were measured to evaluate the safety and efficacy of bridging anticoagulation in this population.&#x0D; Results&#x0D; Ischemic cerebrovascular events occurred following 2 bridged episodes compared to 4 non-bridged episodes (6% vs. 5%, p=0.895). Hemolysis occurred following 1 bridged episode compared to 3 non-bridged episodes (3% vs. 4%, p=0.794). Bleeding events occurred after 4 bridged episodes compared to 13 non-bridged episodes (12% vs. 17%, p=0.474). In a subgroup of patients with either a CHA2DS2-VASc score &gt; 3 or a history of atrial fibrillation, thromboembolic events occurred only in those who did not receive bridging anticoagulation although this result was not statistically significant.&#x0D; Conclusions&#x0D; There was no benefit associated with the routine use of bridging anticoagulation in a general population of stable LVAD outpatients with subtherapeutic INR. A trend towards benefit was seen in a subset of patients with a CHA2DS2-VASc score of &gt; 3 or a history of atrial fibrillation.

17th Biennial European Meeting of the Society for Medical Decision Making Leiden, the Netherlands, June 10-12, 2018.

Purpose: For atrial fibrillation (AF) patients receiving vitamin K antagonists (VKAs), careful management of anticoagulation is important around surgical procedures to minimize the stroke and bleeding risks. If the VKA needs to be stopped periprocedurally to reduce the risk of bleeding, a decision needs to be made whether to bridge this period with a low-molecular weight heparin (LMWH). We aimed to develop a model to compare two periprocedural strategies for AF patients that have to interrupt VKA treatment: administering a LMWH or forgoing bridging therapy. Method(s): A probabilistic Markov model was developed to simulate both a bridge and a non-bridge cohort of AF patients periprocedurally. Modelled events were based on the clinically used CHA2DS2-VASc and HAS-BLED stroke and bleeding prediction rules. To predict strokes, INR values were considered. Quality-adjusted life expectancy, based on the beforementioned clinical endpoints, was the main outcome considered. Result(s): The base case analysis shows that bridging anticoagulation increases the bleeding rate, but reduces the stroke rate. Bridging may be beneficial for patients with a CHA2DS2-VASc scores of 6 or higher and HAS-BLED scores of 0 to 2. For expected shorter periods to reach therapeutic INR, bridging therapy is less likely to be beneficial. Conclusion(s): For patients at high risk of bleeding, bridging anticoagulation Is not likely to be beneficial. For patients at high risk of stroke and low risk of bleeding, bridging anticoagulation may result in additional quality adjusted life years. INR management is an important factor to consider periprocedurally when making the decision whether to bridge.