Prior Bleeding Research Articles

Emerging technologies in the age of big data

Little is known about the role of left atrial appendage closure using the Watchman device (Boston Scientific) in patients who are at very high risk for stroke.The purpose of this study was to assess the role of Watchman in patients with CHA2DS2-VASc ≥5.All patients undergoing procedures for Watchman implant at our institution were enrolled in a prospective registry. All 104 consecutive recipients with CHA2DS2-VASc ≥5 were included.Median patient age was 78.5 ± 6.4 years, 56% were male, mean CHA2DS2-VASc was 5.7 ± 0.9, and mean HASBLED was 4.0 ± 1.0. Indications for implantation were significant prior bleeding (73%), unacceptable bleeding risk (21%), and unacceptable stroke and bleeding risk (6%). Watchman implantation was successful in all patients. All but 2 patients completed 45 days of postprocedural anticoagulation; 56% used warfarin and 44% used a novel oral anticoagulant. Transesophageal echocardiogram at 45 days revealed no significant peridevice leak. One patient was found to have a small mobile, filamentous echodensity attached on the medial aspect of the Watchman device. This resolved with longer anticoagulation with dabigatran and did not result in adverse outcome. At 1-year follow up, ischemic stroke had occurred in 3 patients (2.8%) at 96, 119, and 276 days after the procedure.In a population of patients with mean CHA2DS2-VASc of 5.7, Watchman implantation seemed to be safe and efficacious, with a residual annual ischemic stroke risk of 2.8%. In an atrial fibrillation population with a similar CHA2DS2-VASc score, the estimated annual risk of stroke is ≈12% off anticoagulation and >4% on warfarin.

An under-recognized high-risk atrial fibrillation population: Analyzing transcatheter mitral valve repair patients for left atrial appendage closure device application.

Identify patients undergoing transcatheter mitral valve repair (TMVR) who could potentially benefit from alternative ischemic stroke prophylaxis utilizing a left atrial appendage closure (LAAC) device. Patients undergoing TMVR have a high incidence of atrial fibrillation (AF). The co-morbidities which qualify them to undergo TMVR also increase their risk of stroke and bleeding, making stroke prophylaxis problematic. We conducted a single-center retrospective study, in which the bleeding and stroke risk of all patients undergoing TMVR for degenerative mitral valve disease were reviewed to determine candidacy for a LAAC device for stroke prevention as an alternative to chronic anticoagulation. AF was present in 122 (62%) of TMVR patients with an average CHA2DS2-VASc score of 3.99. 23% of TMVR patients had a history of prior major bleeding event, predominately gastrointestinal bleed. Fifty-three and 47% of TMVR patients were at high or intermediate risk of bleeding, respectively, according to their HAS-BLED score. 50% of patients undergoing TMVR would qualify for LAAC device based on risk assessments. Patients undergoing TMVR represent a high risk group of AF patients that may benefit from a LAAC device.

Evaluating Real-World Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology: Final 2-Year Outcome Data of the EWOLUTION Trial Focusing on History of Stroke and Hemorrhage.

Left atrial appendage occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. Evaluating real-life clinical outcomes in atrial fibrillation patients receiving the WATCHMAN left atrial appendage closure technology was designed to collect prospective multicenter outcomes of thromboembolic events, bleeding, and mortality for patients implanted with a WATCHMAN in routine daily practice. One thousand twenty patients with a WATCHMAN implant procedure were prospectively followed in 47 centers. Left atrial appendage occlusion indication was based on the European Society of Cardiology guidelines. Follow-up and imaging were performed per local practice up to a median follow-up of 2 years. Included population was old (age 73.4±8.9 years), at high risk for stroke (311 prior ischemic stroke/transient ischemic attack and 153 prior hemorrhagic stroke) and bleeding (318 prior major bleeding), with CHA2DS2-VASc score ≥5 in 49%, hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, Labile international normalized ratio, elderly, drugs/alcohol concomitantly ≥3 in 40% and oral anticoagulation contraindication in 72%. During follow-up, 161 patients (16.4%) died, 22 strokes were observed (1.3/100 patient-years, 83% reduction versus historic data), and 47 major nonprocedural bleeding events (2.7/100 patient-years, 46% reduction versus historic data). Stroke and bleeding rates were consistently lower than historic data in those with prior ischemic (-76% and -41%) or hemorrhagic (-81% and 67%) stroke and prior bleeding (-85% and -30%). Lowest bleeding rates were seen in patients with early discontinuation of dual antiplatelet therapy. Patients with early discontinuation of antithrombotic therapy showed lower bleeding rates, while they were highest for those with prior bleeding. Device thrombus was observed in 34 patients (4.1%) and was not correlated to drug regimen during follow-up ( P=0.28). During the complete 2-year follow-up of Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology, patients with a WATCHMAN left atrial appendage occlusion device had consistently low rates of stroke and nonprocedural bleeding, although most were contraindicated to oral anticoagulation and used only single antiplatelet therapy or nothing. URL: https://clinicaltrials.gov . Unique identifier: NCT01972282.

Evaluation of Blood Clot, Platelet-rich Plasma, Platelet-rich Fibrin, and Platelet Pellet as Scaffolds in Regenerative Endodontic Treatment: A Prospective Randomized Trial

IntroductionRegenerative endodontic procedures (REPs) using autologous platelet concentrates as scaffolds can improve the biologic outcome of treatment. This prospective, randomized trial compared the clinical and radiographic performance of REPs using platelet-rich plasma (PRP), platelet-rich fibrin (PRF), a platelet pellet (PP), and an induced blot clot (BC). MethodsSixty-seven healthy children (aged 8–11 years) with 88 immature necrotic incisors were included. After the root canal disinfection step, the teeth were randomly assigned into 1 of the following groups (n = 22/group) according to the scaffold used: PRP, PRF, PP, and BC. In the PRP, PRF, and PP groups, the platelet concentrates were introduced into the root canal without prior induction of apical bleeding. Treatment outcomes were assessed using a combined clinical and radiographic scoring system, whereas the changes in root dimensions were compared using linear measurements of root length and width with ImageJ (National Institutes of Health, Bethesda, MD) and Turboreg (Biomedical Imaging Group, Swiss Federal Institute of Technology, Lausanne, Switzerland) and planar measurements using the radiographic root area (RRA) and radiographic canal area (RCA) techniques. One-way analysis of variance, the Duncan multiple range test, the Kruskal-Wallis test, the Mann-Whitney U test, and chi-square dependency tests were used for statistical analysis of data (all P = .05). ResultsExcept for 2 teeth in the PRF and BC groups, all teeth showed similar and high success scores (periapical healing, radiographic root development, and positive response to sensitivity tests) after an average follow-up time of 28.25 ± 1.2 months. Of all teeth, 73.9% showed complete apical closure with similar closure rates among groups (P > .05) and a greater tendency for conical-shaped apical closure than a blunt apex. Although linear measurements indicated a similar increase in root length and width among all groups (P > .05), the RRA of the BC group was significantly greater than those of the PRF and PP groups, and the RCA of the BC group was significantly greater than PRP, PRF, and PP (all P < .05) when the follow-up time was not used as a factor. Eighty-six percent of the teeth showed a positive response to sensitivity tests with similar initial response times (P > .05). ConclusionsPRP, PRF, and PP can yield similar clinical and radiographic outcomes to BC without the need for prior apical bleeding and with significantly less tendency for root canal obliteration. RRA and RCA may reveal minor differences that cannot be determined by linear measurements.

Prediction Model for Significant Bleeding in Patients with Supratherapeutic International Normalized Ratio After Oral Administration of Warfarin.

The use and range of indications for anticoagulation therapy are steadily growing. The objective of this study was to develop a scoring model to predict the occurrence of significant bleeding in patients taking warfarin with a supra-therapeutic international normalized ratio. Data were collected from the medical records of patients taking warfarin with an international normalized ratio > 3.5. The characteristics of bleeding episodes and the need for transfusion of blood products were recorded. Regression models were constructed to predict the occurrence of significant bleeding (requiring a transfusion of more than 2units of packed red blood cells, intrapericardial or intracranial hemorrhage). The predictive values of previously published scores (ATRIA: anemia, hypertension, severe renal disease, age ≥ 75years, or prior bleeding history; and ORBIT: old, reduced hemoglobin, bleeding history, kidney insufficiency or antiplatelet treatment) were compared with our New Bleeding Score (NBLDSCOR); the areas under the curve for the receiver-operating characteristic plots were compared using a non-parametric DeLong test. Significant bleeding was reported in 87 out of 389 admitted patients. With an area under the curve of 0.736 ± 0.032, NBLDSCOR was the best predictor of significant bleeding in this population. Neither ATRIA nor ORBIT was a good predictor of significant bleeding, where the area under the curve for the receiver-operating characteristic plot for ATRIA was 0.654 ± 0.034 and for ORBIT was 0.604 ± 0.033. The predictive power of NBLDSCOR was superior to ATRIA and ORBIT (p < 0.001), while there was no meaningful difference in the predictive powers of ATRIA and ORBIT. The NBLDSCOR including age, negative Rhesus factor, low hemoglobin, renal impairment, and concomitant peptic ulcer and disseminated cancer is a good predictor of significant bleeding in this patient population.

Performance of the ABC Scores for Assessing the Risk of Stroke or Systemic Embolism and Bleeding in Patients With Atrial Fibrillation in ENGAGE AF-TIMI 48.

The ABC (age, biomarker, clinical history)-stroke and ABC-bleeding risk scores incorporate clinical variables and cardiovascular biomarkers to estimate risk of stroke or systemic embolic events and bleeding, respectively, in patients with atrial fibrillation. These scores have been proposed for routine clinical use, but their performance in external cohorts remains uncertain. ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a multinational randomized trial of the oral factor Xa inhibitor edoxaban in patients with atrial fibrillation and a CHADS2 score ≥2. We performed a nested prospective biomarker study in 8705 patients, analyzing baseline high-sensitivity troponin T (hsTnT), NT-proBNP (N-terminal B-type natriuretic peptide), and growth differentiation factor-15 (GDF-15), as well as in serial samples after 12 months. The ABC-stroke (age, prior stroke/transient ischemic attack, hsTnT, NT-proBNP) and ABC-bleeding (age, prior bleeding, hemoglobin, hsTnT, and GDF-15) scores were tested. Hazard ratios were adjusted for estimated glomerular filtration rate and the components of the CHA2DS2-VASc and HAS-BLED scores, respectively. Discrimination and reclassification were compared with these established scores. Median baseline hsTnT, NT-proBNP, and GDF-15 levels were 13.7 ng/L (25th-75th percentiles, 9.6-20.4 ng/L), 811 pg/mL (386-1436 pg/mL), and 1661 pg/mL (1179-2427 pg/mL), respectively. Elevated hsTnT, NT-proBNP, and GDF-15 were independently associated with higher rates of stroke or systemic embolic events, and elevated hsTnT and GDF-15 were independently associated with higher rates of major bleeding ( P<0.001 for each). The ABC-stroke and ABC-bleeding scores were well calibrated and yielded higher c indexes than the CHA2DS2-VASc score for stroke or systemic embolic events (0.67 [95% CI, 0.65-0.70] versus 0.59 [95% CI, 0.57-0.62]; P<0.001) and HAS-BLED score for major bleeding (0.69 [95% CI, 0.66-0.71] versus 0.62 [95% CI, 0.60-0.64]; P<0.001), respectively. The ABC-stroke and ABC-bleeding scores stratified patients within CHA2DS2-VASc and HAS-BLED risk categories ( P<0.001 for both). Patients with ABC-bleeding scores predicting a high 1-year risk of bleeding (>2%) derived greater benefit from treatment with edoxaban compared with warfarin. The ABC-stroke and ABC-bleeding scores evaluated in this anticoagulated clinical trial cohort were well calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively. These scores may help identify patients most likely to derive a benefit from treatment with non-vitamin K antagonist oral anticoagulants. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00781391.

A phase Ib trial of anti-VEGFR/PDGFR vorolanib combined with immune checkpoint inhibitors (CPIs) in solid tumors.

TPS472 Background: Immune CPIs have become a standard treatment option for many advanced malignancies, including gastric (G)/GE junction (GEJ) and hepatocellular cancer (HCC), but resistance is inevitable. Data suggests angiogenesis plays a key role in tumor-mediated immune regulation. Vascular endothelial growth factor (VEGF) can inhibit intra-tumor T cell trafficking, while anti-VEGF therapy can improve T cell infiltration, potentially enhancing response to CPIs to overcome resistance. Vorolanib (V), a potent oral VEGFR/PDGFR inhibitor, has anti-angiogenic properties with a favorable toxicity profile. This phase 1b study is aimed to assess the safety and efficacy of V + CPIs, pembrolizumab (P) or nivolumab (N), in pts with advanced solid tumors. Methods: The primary objective is to determine the recommended phase 2 dose (RP2D) of V + CPIs. Secondary objectives include safety, toxicity and objective response rate (ORR) and survival outcomes. Correlatives include analysis of angiogenic factors and tumor infiltrating lymphocytes as response biomarkers in archived tumor tissue and peripheral blood. Key eligibility for dose escalation cohort includes pts with solid tumors who can receive standard P or N, and for dose expansion cohort includes pts with PD-L1+ G/GEJ cancer who progressed on one or two lines of chemo, refused or are not candidates for chemo; or HCC Child-Pugh A treated with or refused sorafenib, ECOG PS 0-1 and adequate organ function. Key exclusions include prior CPI, significant bleeding, thrombosis, autoimmune disease or condition requiring corticosteroid use. A 3+3 design will be utilized to determine maximum tolerated dose and RP2D. V starts at 300 mg PO daily, pts receive N 480 mg IV Q 28-day cycle or P 200 mg IV Q 21-day cycle (max 36 pts). Dose level advancement occurs when all pts complete cycle 1 of assessed level. 20 additional pts (10 HCC, 10 G/GEJ cancer) will be treated at RP2D. Response assessment by RECIST v1.1 occurs Q 3 cycles on P or Q 2 cycles on N. ORR of 20% or greater warrants further investigation. Enrollment is ongoing. Clinical trial information: NCT03511222.

World trauma education: hemorrhage control training for healthcare providers in India

BackgroundHemorrhage remains a major cause of death around the world. Eighty percent of trauma patients in India do not receive medical care within the first hour. The etiology of these...

Real World Experience of Direct Oral Anticoagulants with Comparison of Safety Outcomes to the Warfarin Era of Venous Thromboembolism Treatment

Introduction:The introduction of direct oral anticoagulants (DOAC) has revolutionised the treatment of atrial fibrillation (AF) and venous thromboembolism (VTE). Previous clinical trials have demonstrated that DOACs are non-inferior to warfarin for treatment and prevention of VTE and at least as safe in terms of bleeding risk. However, there is limited data on real-world outcomes. We aim to evaluate the local real-world DOAC use with particular focus on safety and to specifically compare the safety outcomes of the warfarin era vs the DOAC era in the management of VTE.Method:Retrospective evaluation was performed with a total of 1696 patients reviewed including demographics and safety outcomes. Patients commenced or continuing on a DOAC for the treatment of AF and VTE at the Northern Hospital, a tertiary hospital in Victoria, Australia (September 2013 to September 2016, n=1079) were identified.A sub analysis was then performed comparing patients on DOAC for VTE indications to a separate retrospective local audit of VTE patients during the warfarin era (July 2011 to December 2012, n=617). For the purpose of the sub analysis, patients with active malignancy and thromboses other than deep vein thrombosis (DVT) and pulmonary embolus (PE) were excluded to maintain consistency with the warfarin era data.Results:A total of 1079 patients on DOAC with median age 70 years (range 17-96) were identified. The indications for DOAC were AF 61.4% (n=663), VTE treatment 30.5% (n=329) and VTE maintenance/prophylaxis 8.1% (n=87). The most commonly prescribed DOAC was rivaroxaban 60.8% (n=656) followed by apixaban 28.7% (n=310) and dabigatran 10.5% (n=113). Of these patients 29.7% (n=320) were on low dose anticoagulation. Forty episodes of clinically significant bleeding (ISTH-SCC score 3-4) (3.7%) were captured [Table 1]. The average HASBLED score of these patients was 2 and significant risk factors for bleeding included low dose anticoagulation, AF patients, concurrent antiplatelet use, prior bleeding and high falls risk.In terms of thrombotic complications, there were 12 episodes of thrombotic stroke (1.8%) despite DOAC use with risk factors including low dose anticoagulation (p=0.03), prior stroke (p=0.04) and high falls risk (p=0.03). Nine patients on DOACs for VTE (2.2%) reported recurrence including a patient with active malignancy.374 patients on DOAC for VTE management were included in the sub-analysis comparison to the warfarin audit (n=617). Of the DOAC patients, 88.2% (n=330) were on rivaroxaban and 11.8% (n=44) were on apixaban - 31.8% (n=315) were on DOAC for acute VTE treatment and 6.0% (n=59) for maintenance or prophylaxis at time of data collection. There were more unprovoked VTE in the DOAC group (66.0% (n=208) vs 42.0% (n=259), p<0.001). The patient demographics are outlined in Table 2. Overall, there were 28 clinically significant bleeding (ISTH-SCC score 3-4) events in the warfarin group (4.5%) and 8 in the DOAC group (2.1%; p=0.05). The sites of bleeding were similar in both groups with gastrointestinal tract bleeding being the most common source. Forty-eight recurrent VTE events were captured - 39 occurred on warfarin (6.3%) and 9 while on DOAC (2.4%; p=0.005).Conclusion:This retrospective audit shows that our local safety outcomes are comparable to clinical trials. Low dose anticoagulation and high falls risk (a surrogate marker of frailty) were significant risk factors for both clinically significant bleeding and thrombotic stroke in the DOAC population. These patients are likely frailer with greater co-morbidities and have shared risk factors for bleeding and stroke, suggesting that for these high risk patients, low dose anticoagulation does not negate their risk of complications and careful prescribing and close monitoring remain essential.The sub-comparison between VTE patients on DOAC and warfarin found that patients on warfarin had a higher rate of VTE recurrence in comparison to patients on DOAC. This may reflect patients maintaining more time on therapeutic anticoagulation with the more predictable DOACs compared to warfarin patients who may have more time below therapeutic range. There may also be a selection bias as-high risk patients with co-morbidities and those not meeting criteria for DOACs continue to be prescribed warfarin in the DOAC era. This data is similar to recent real-life DOAC experience in the atrial fibrillation population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Predictors of Remission in Adults with Immune Thrombocytopenia Treated with Romiplostim

Background: In adults with ITP, thrombopoietin receptor agonists (TPO-RA) are often assumed to be lifelong therapy. However, some patients achieve treatment-free remission (TFR) by maintaining hemostatic platelet counts after discontinuing TPO-RA, despite not replacing them with other ITP medications. Predictors of safely discontinuing romiplostim have varied across studies. In an analysis of 8 romiplostim studies, 27 patients achieved TFR; more remitters than nonremitters had ITP for Aim: This multivariate analysis integrated data across multiple romiplostim studies in adults with ITP to explore predictors of TFR. Methods: Data were pooled for 911 romiplostim-treated patients in 13 ITP studies conducted from 2002 to 2014. All patients failed first-line treatments before study enrollment. Secondary thrombocytopenia patients were excluded. Romiplostim treatment was discontinued per dosing rules; 1 study included a forced taper after 1 year of romiplostim. Typically, the romiplostim dose was reduced for platelet counts >200×109/L and withheld, then reduced, for platelet counts >400×109/L. Concomitant ITP medication could be reduced for platelet counts >50×109/L. TFR was defined as a ≥6-month treatment-free period with platelet counts consistently ≥50×109/L. Univariate analysis with logistic regression examined potential predictors of TFR, including age, sex, ITP duration, prior splenectomy, platelet count (baseline and first 4 weeks), bleeding in the first 6 months, and baseline concurrent therapy. Multivariate analysis with logistic regression evaluated significant predictors from the univariate analysis. Results: TFR was achieved by 61 ITP study patients who received romiplostim. For remitters vs nonremitters, median baseline age was 53 years in both cohorts; 57% vs 61% were female; and 93% vs 88% were Caucasian (Table 1). Median ITP duration at study baseline was 0.5 years among remitters and 3.5 years among nonremitters. Prior splenectomy occurred in 21% of remitters and 36% of nonremitters. The number of prior ITP treatments was ≤3 for 74% of remitters and 39% of nonremitters. Baseline platelet count was 12 months (chronic; odds ratio [OR], 4.275; P Conclusions: In this integrated analysis of 911 adult ITP patients across 13 studies, shorter ITP duration at baseline (≤12 months) was an independent predictor of TFR. Neither previous splenectomy (which predicted TFR in 1 study) nor bleeding were independent predictors of TFR in this much larger analysis. In total, these results imply that earlier use of romiplostim in adults with ITP could be associated with greater likelihood of achieving TFR. Future studies should also explore biologic variables as predictors of TFR. Disclosures Newland:Amgen Inc., Angle, Dova Pharmaceuticals, Argenx, Rigel, Shionogi, Novartis: Consultancy; Amgen Inc., GlaxoSmithKline, and Novartis: Research Funding; Novartis: Speakers Bureau. Bussel:Uptodate: Honoraria; Protalex: Consultancy; Momenta: Consultancy; Rigel: Consultancy, Research Funding; Prophylix: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Amgen Inc.: Consultancy, Research Funding. Bird:Amgen, Novartis: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau. Arnold:Novartis: Consultancy, Research Funding; UCB: Consultancy; UCB: Consultancy; Bristol Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Kessler:Novo Nordisk: Honoraria, Research Funding; Biomarin: Research Funding; Genentech: Research Funding; Dimension Advisory boards: Membership on an entity9s Board of Directors or advisory committees; DSMB: Membership on an entity9s Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Sangamo: Research Funding; Bayer: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Mayer:Novartis: Research Funding; Amgen: Research Funding. Janssens:Roche: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Other: Ad board, Speakers Bureau; Novartis: Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy, Speakers Bureau; Sanofi-Genzyme: Speakers Bureau; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Other: Ad board, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Wang:Amgen: Employment, Equity Ownership. Eisen:Amgen Inc.: Employment, Equity Ownership.

Outcomes beyond the Third Month of Anticoagulation in Patients Aged &gt;75 Years with a First Episode of Unprovoked Venous Thromboembolism

Background The ideal duration of anticoagulant therapy in elderly patients with unprovoked venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE ( R egistro I nformatizado E nfermedad T rombo E mbólica) registry to compare the rate and severity of pulmonary embolism (PE) recurrences versus major bleeding beyond the third month of anticoagulation in patients >75 years with a first episode of unprovoked VTE. Results As of September 2017, 7,830 patients were recruited: 5,058 (65%) presented with PE and 2,772 with proximal deep vein thrombosis (DVT). During anticoagulant therapy beyond the third month (median, 113 days), 44 patients developed PE recurrences, 36 developed DVT recurrences, 101 had major bleeding, and 241 died (3 died of recurrent PE and 19 of bleeding). The rate of major bleeding was twofold higher than the rate of PE recurrences (2.05 [95% confidence interval, CI: 1.68–2.48] vs. 0.90 [95% CI: 0.66–1.19] events per 100 patient-years) and the rate of fatal bleeding exceeded the rate of fatal PE events (0.38 [95% CI: 0.24–0.58] vs. 0.06 [95% CI: 0.02–0.16] deaths per 100 patient-years). On multivariable analysis, patients who had bled during the first 3 months (hazard ratio [HR]: 4.32; 95% CI: 1.58–11.8) or with anemia at baseline (HR: 1.87; 95% CI: 1.24–2.81) were at increased risk for bleeding beyond the third month. Patients initially presenting with PE were at increased risk for PE recurrences (HR: 3.60; 95% CI: 1.28–10.1). Conclusion Prolonging anticoagulation beyond the third month was associated with more bleeds than PE recurrences. Prior bleeding, anemia, and initial VTE presentation may help decide when to stop therapy.

The Long Life of a Clip

Hemoclips are a very common and effective intervention used during colonoscopies to stop immediate bleeding. A recent survey of VA gastroenterologists reported that when hemostatic treatment was applied, 76% of physicians preferred a hemoclip.1 Although hemoclips are very common, there are no clear established guidelines for their use. Hemoclips typically fall off on their own within 1-2 weeks. However, there have been an increased number of cases where clips have been found as long as 2 years later.6,7 Here we describe a case of retained hemoclip for over one year and discuss the possible implications of such clips<./p> A 67 year old African American man with a history of multiple GI bleeds, iron deficiency anemia, CAD, paroxysmal Afib, and CVAs presented to the GI endoscopy suite for colonoscopy to evaluate iron deficiency anemia. One 10mm TA was removed by cold snare polypectomy in the cecum. Two TA in the ascending colon were also removed. No hemoclips were placed. Several days later, patient had significant GI bleed while on dual antiplatelet therapy after recent NSTEMI. EGD was normal. On colonoscopy, post-polypectomy sites seen in the cecum and ascending colon showed evidence of bleeding stigmata. 3 hemoclips were placed in the cecum and 1 was placed in ascending colon achieving hemostasis. Numerous hyperplastic polyps were also seen in the rectosigmoid colon with the plan to remove them in one year once off anti-platelets. On repeat colonoscopy 1 year later, 3 flat hyperplastic polyps were removed. Interestingly, a clip was also seen in the cecum at the site of the prior post polypectomy bleed. The case presented here is another example of hemoclips staying in place much longer than expected. While hemoclips can be excellent tools to achieve hemostasis, they are not completely benign. They are contraindications to MRI, and two years after endoscopy hemoclips would likely not have been considered. Abdominal radiographs have been suggested as a possible way to screen for retained clips prior to MRI.7 There has also been a case report of a GI bleed resulting from focal ulceration at the base of a retained clip, therefore these retained clips may pose as a risk factor for future bleeding.8 In scenarios where large polyps are removed, persistence of clips could interfere with detecting and treating any residual polyps<.sup>9 Therefore, it is important for physicians to consider these possible complications prior to placing hemoclips<./p>2933_A Figure 1. Hemoclip placed in cecum to achieve hemostatis after GI bleed.2933_B Figure 2. Retained hemoclip on colonoscopy over one year later.

Role of Pre-LVAD Endoscopic Screening and Assessment of Risk Factors Associated With Post-LVAD Implantation Gastrointestinal Bleeding

Introduction: Left Ventricular Assist Devices (LVAD) occupy a key place in treatment for end-stage heart failure. However, around 20 - 30 % of the patients present with post-implant gastrointestinal bleed (GIB). To effectively manage the GIB in this patient population, it is vital to understand the associated risk factors and demographic parameters. Hence, we conducted this study to assess the role of pre-LVAD endoscopic screening in this population and to identify the risk factors associated with post-LVAD GIB. Methods: We performed a retrospective study at a single academic tertiary care referral center in patients who had Heart Mate IITM LVAD placed between 2010 and 2017. Various parameters, including patient demographic data, pre-LVAD endoscopic findings, history of prior GI bleed, time between LVAD implantation and admission for GIB, LVAD settings, laboratory data during admission, and endoscopic intervention utilized were analyzed. The statistical analysis was conducted using SAS v9.4. Results: 68 patients had LVAD implanted between 2011 and 2017. 25/68 patients (36.7%) had at least one admission for a GIB. Both groups (bleeders vs. non-bleeders) were similar in their demographics, pre-LVAD endoscopic screening procedures and findings (Table 1). However, those that presented with GIB were more likely to have a history of GIB prior to the implantation (p = 0.037) and an increased LVAD power (p= 0.05) (Table 1). 68% of the patients with GIB presented to the hospital within 1 year of implantation and 88% were managed in the non-ICU setting. EGD was performed in 67 % of the GIB patients and 77% of the endoscopic procedures were done within 2 days of admission. Of the patients that presented with GIB, 36% had multiple readmissions (Table 2). Compared to patients with a single GIB, the patients with multiple GIB had an increased LVAD power (p=0.036) and lower admission hemoglobin (p=0.006) (Table 2). Further, analysis revealed that patients with 3 or more readmissions for GIB had a significantly higher percentage of their first admission within 90 days of LVAD implantation (p=0.012) (Table 3). Conclusion: No significant association was seen between pre-LVAD endoscopic screening and post-LVAD admission for GIB was noted. History of prior GIB increases the risk of GIB in LVAD patients. A higher LVAD power and shorter median time between LVAD implantation and first admission (< 90 days) for GIB are significantly associated with recurrent GIB hospitalizations.567_A Figure 1 No Caption available.567_B Figure 2 No Caption available.567_C Figure 3 No Caption available.

Inappropriate use and overuse of PPIs: A strategy for discontinuation

Proton pump inhibitors (PPIs) have risks associated with long-term use, yet they are used chronically by more than 20 million Americans and account for more than $10 billion in health care spending.1https://apha.us/IMSInstituteGoogle Scholar Data on the effects of long-term PPI use are still emerging, but potential consequences include increased risk of vitamin and mineral deficiencies, bone fractures, changes in gut microbiota, Clostridium difficile–associated diarrhea, pneumonia, dementia, chronic kidney disease, gastric atrophy (higher risk among those with Helicobacter pylori infections), and gastric cancer. Overprescribing PPIs is common, with as many as 68.8% of patients being prescribed a PPI inappropriately at hospital discharge2J Manag Care Pharm. 2010; 16: 122-129PubMed Google Scholar and 36% to 39% of ambulatory patients lacking an indication for PPI use.3Am J Manag Care. 2010; 16: e228-e234PubMed Google Scholar, 4Am J Gastroenterol. 2003; 98: 51-58Crossref PubMed Scopus (113) Google Scholar As pharmacists, we can make an impact on inappropriate use and overuse of PPIs. At Central Pharmacy in Durham, NC, we initiated a service as part of a residency project to tackle the issue of PPI overuse. Our approach is to taper the PPI gradually while increasing the duration between each step to improve successful PPI discontinuation. The taper involves use of compounded omeprazole capsules, which allows the patient to decrease their PPI dose by 5 mg every 2 weeks. This regimen is also accompanied by lifestyle changes and supplements to support digestion and gastrointestinal (GI) health. Abrupt withdrawal of PPIs results in successful discontinuation in only 14% to 27% of patients who have used these medications for 8 weeks.5Eur J Gastroenterol Hepatol. 2010; 22: 1182-1188Crossref PubMed Scopus (26) Google Scholar, 6Int J Family Med. 2015; 2015: 175436Crossref PubMed Google Scholar Our goal is to have a higher success rate by tapering more gradually. Patients on step-down therapy with omeprazole 20 mg daily for 1 week, omeprazole 10 mg for 1 week, and omeprazole 10 mg every other day for 1 week saw slightly higher success rates, with 31% achieving discontinuation.7Aliment Pharmacol Ther. 2006; 24: 945-954Crossref PubMed Scopus (117) Google Scholar For our PPI discontinuation service, we first establish patient interest and eligibility. Patients ineligible for PPI discontinuation include those with Barret’s esophagus, Zollinger–Ellison disease, Los Angeles grade C or D erosive esophagitis, or idiopathic peptic ulcer disease. Other ineligible patients are those on nonselective NSAIDs at high risk of a GI bleed, those on COX-2 selective NSAIDs with a prior GI bleed, and those on antiplatelet therapy at high risk of a GI bleed. Once eligibility is determined, patients schedule a consult with a pharmacist to determine trigger foods and the potential need for supportive supplements on the basis of patient-specific symptoms. The patient’s daily PPI dose is converted to omeprazole equivalents to calculate the taper regimen that will be requested from the physician. If the patient receives 20 mg of omeprazole equivalent each day, their regimen will consist of omeprazole 15 mg for 2 weeks, omeprazole 10 mg for 2 weeks, and finally omeprazole 5 mg for 2 weeks. Patients are also provided with 5-mg capsules for breakthrough reflux symptoms. Follow-up with a pharmacist occurs by phone every 2 weeks to align with the time frame of the taper regimen. These phone calls assess patient symptoms and determine if any adjustments need to be made to the plan. We encourage patients to call the pharmacist whenever they need to report symptoms that are not responding to the breakthrough omeprazole. This project is under way, and as it progresses, we will collect metrics on frequency of rebound symptoms and success rate of discontinuation at 1, 3, and 6 months after conclusion of the PPI taper.

Contemporary Burden and Correlates of Symptomatic Paroxysmal Supraventricular Tachycardia.

BackgroundContemporary data about symptomatic paroxysmal supraventricular tachycardia (PSVT) epidemiology are limited. We characterized prevalence and correlates of symptomatic PSVT within a large healthcare delivery system and estimated national PSVT burden.Methods and ResultsWe identified adults with an encounter for potential PSVT between 2010 and 2015 in Kaiser Permanente Northern California, excluding those with prior known atrial fibrillation or atrial flutter. We adjudicated medical records, ECGs, and other monitoring data to estimate positive predictive values for targeted International Classification of Diseases (ICD), 9th and 10th Revisions codes in inpatient, emergency department, and outpatient settings. Combinations of diagnosis codes and settings were used to calculate PSVT prevalence, and PSVT correlates were identified using multivariable regression. We estimated national rates by applying prevalence estimates in Kaiser Permanente to 2010 US Census data. The highest positive predictive values included codes for “PSVT” in the emergency department (82%), “unspecified cardiac dysrhythmia” in the emergency department (27%), “anomalous atrioventricular excitation” as a primary inpatient diagnosis (33%), and “unspecified paroxysmal tachycardia” as a primary inpatient diagnosis (23%). Prevalence of symptomatic PSVT was 140 per 100 000 (95% confidence interval, 100–179) and was higher for individuals who were older, women, white or black, or who had valvular heart disease, heart failure, diabetes mellitus, lung disease, or prior bleeding. We estimate the national prevalence of symptomatic PSVT to be 168 per 100 000 (95% confidence interval, 120–215).ConclusionsSelected diagnostic codes in inpatient and emergency department settings may be useful to identify symptomatic PSVT episodes. We project that at least 0.168% of US adults experience symptomatic PSVT, and certain characteristics can identify people at higher risk.

Perceived advantages and disadvantages of oral anticoagulants, and the trade-offs patients make in choosing anticoagulant therapy and adhering to their drug regimen

ObjectiveThe objective of this study was to explore the perceived advantages and disadvantages of oral anticoagulant therapies (OAT), and the trade-offs patients make in choosing therapy and adhering to their drug regimen. MethodsFive focus group sessions were conducted across Europe among patients with atrial fibrillation to identify the most important factors impacting OAT‘s value and adherence. ResultsThe most frequently identified barriers to OAT were lack of knowledge; poor patient-physician relationships; distraction due to employment or social environment; prior bleeding event(s) or the fear of bleeding; and changes in routine. Factors identified as promoting adherence included patients' personality, motivation, attitudes, and medication-taking habits and routines, as well as good quality health services. Inconvenient aspects of vitamin-K antagonists, such as regular blood monitoring and diet restrictions, were not reported to influence adherence, but may trigger patients to switch to direct oral anticoagulants. ConclusionMost patients reported that a mixture of modifiable and non-modifiable factors helps them to take their drugs as prescribed. Individual patients’ particular needs and preferences regarding OAT vary. Practice implicationsOAT adherence can be promoted if therapies are tailored to patients’ needs and preferences. Patients should be supported to share their preferences with their clinician.

Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism: comment

Kuperman et al. found that patients with anemia had a higher risk of major bleeding (RR 2.84; 95% CI 2.52-3.39) in RIETE database. Anemia appeared to be an independent predictive factor for major bleeding [hazard ratio (HR) 1.95; 95% CI 1.72-2.20] in this registry. Unfortunately, selection bias due to enrolled patients does not allowed us to use these major results in ambulatory care. The aim of SCORE study was to refine bleeding risk estimation in French vitamin K antagonist (VKA) treated patients and to identifying one or several parameters of prognostic significance. We conducted a prospective, multi-center cohort study of 962 consecutive outpatients from private angiologic offices, clinics and hospitals enrolled in grenoble angiologic network for thromboembolic diseases between May 2009 and December 2010, followed during 1year by their general practitioner. Main outcome was the occurrence of major bleeding or clinically non major relevant bleeding (CNMRB). Incidence rates major bleeding and CNMRB were 2.86 (95% CI 1.95-4.2) events per 100 patient-years and 12% (95% CI 9.89-14.11) respectively. Cox multivariate analyses showed that only anemia was strongly associated with a risk of major bleeding (HR 6.1; 95% CI 2.7-13.8; p = 0.001). Logistic regression analyses performed in CNMRB showed that anemia, prior gastro-intestinal bleeding and antiplatelet drug use were strongly associated with a risk of CNMRB at 1 year, respectively OR 2.53, 95% CI (1.4-4.56); p = 0.002, OR 3.32, 95% CI (1.51-7.31); p = 0.003 and OR 1.77, 95% CI (1.1-2.83); p = 0.017. These new data were consistent between major and CRNM bleeding in VKA treated patients. The key role of anemia should be confirmed in other prospective cohort studies, with different anticoagulants use such as direct oral anticoagulant in ambulatory care settings.

Medically Clear

Medically Clear

Serendipitous Discovery of Factor VII Deficiency and the Ensuing Dilemma

Congenital factor VII deficiency is a challenging disorder to manage, as it is associated with varied genotypes that do not clinically correlate with a bleeding phenotype. Individuals with severe factor VII deficiency (FVII: c <1%) might be asymptomatic, while patients with moderate deficiency (FVII: c level >5%) may experience severe hemorrhages. In modern medicine, due to extensive routine pre-operative laboratory testing, clinically asymptomatic patients without any bleeding history might be incidentally discovered, raising clinical dilemmas. Careful consideration of bleeding versus thrombosis risk has to be made in such cases, especially in the elderly. Clinical history of no prior bleeding complications may be a reassuring factor. Minimal required replacement dosing of recombinant activated factor VII can be given peri-operatively in such situations, with close monitoring.

Suitability for Watchman Implantation in TAVR Patients with Atrial Fibrillation

ABSTRACTBackground: We assessed the suitability for Watchman in transcatheter aortic valve replacement (TAVR) patients with atrial fibrillation (AF). Patients who undergo TAVR and have AF are at high-risk of stroke, major bleeding, and death. The Watchman device is now available as an alternative to anticoagulation (OAC) for stroke prevention in selected patients.Methods: We reviewed medical records of 113 patients who underwent TAVR for severe aortic stenosis (AS) with high- or extreme-surgical risk. We estimated the CHA2DS2VASC and HAS-BLED scores and investigated the presence of approved indications for the Watchman device in patients with AF.Results: Of the 113 patients, 48 (43%) had AF. CHA2DS2VASC score ≥3 was seen in 46 (96%) patients. A total of 31 (65%) AF patients had a high bleeding risk, comprised of HAS-BLED score ≥4 in 29 (60%), prior bleeding in 18 (38%) and both in 16 (33%). Warfarin was used for stroke prevention in 38 (80%) patients. At least one approved indication for Watchman was found in 44 (92%) patients: prior bleeding in 18 (38%); labile international normalized ratios (INR) in 24 (50%); non-adherence to oral anticoagulation (OAC) 6 (13%); prior falls in 30 (63%) and fall risk in 37 (77%) patients.Conclusions: Chronic OAC remains the mainstay of treatment in TAVR patients with AF. More than 90% of such patients have an appropriate indication for Watchman implant, stemming from their high stroke and bleeding risk. Our findings suggest an unmet need for Watchman in this population.