Acute Bleeding Events Research Articles

Outcomes of Transcatheter Aortic Valve Implantation in Nonagenarians Compared to Younger than 90 Year Old Patients

BackgroundGiven that life expectancy has improved, nonagenarians have become a significant proportion of world population. As aortic stenosis is primarily a disease of the elderly, the need for invasive cardiac approaches is expected to increase in people of extreme age. Herein, we compare the in-hospital adverse clinical outcomes and mortality after transcatheter aortic valve implantation (TAVI) procedures in nonagenarians to younger than 90 year old patients. MethodsA retrospective study was conducted on 1336 patients who underwent TAVI between January 2016 and March 2020 at Toulouse University Hospital, Rangueil, France. Post-TAVI adverse clinical outcomes were defined according to Valve Academic Research Consortium-2 Criteria. The studied population was divided into 2 groups according to age. ResultsOut of 1336 patients, 250 (18.7%) were nonagenarians with a mean age of 91.8 ± 1.9 years. Pacemaker implantation (12.4% vs 12.1%), stroke (2% vs 1.8%), and major vascular complications (9.2% vs 6.7%) were more common in nonagenarians, whereas acute kidney injury (1.2% vs 2.7%) and major bleeding events (3.2% vs 3.4%) were more common in the <90-year-old group. Nonagenarians are more likely to develop major vascular complications (odds ratio [OR] = 1.76 95% confidence interval [CI] 1.04-3, P = .03). The prevalence of in-hospital mortality in nonagenarians and <90-year-old patients were 5.2% and 2%, respectively. Survival analysis showed a significant difference in mortality during hospitalization period only ( P = .04). ConclusionThe prevalence of TAVI procedural success is remarkably high in nonagenarians and comparable to that of younger patients. However, the in-hospital mortality rate was 2-fold more than that of <90-year-old patients.

Outcomes of transcatheter aortic valve implantation in nonagenarians compared to &lt; 90 years patients

Given that life expectancy has been improved, nonagenarians become a significant proportion of world population. As aortic stenosis is primarily a disease of the elderly, the need for invasive cardiac approaches is expected to increase in people of extreme age We compare the in-hospital adverse clinical outcomes and mortality after TAVI procedures in nonagenarians to < 90 years patients. A retrospective study was conducted on 1336 patients who underwent TAVI at Toulouse University hospital, Rangueil, France. Post-TAVI adverse clinical outcomes were defined according to Valve Academic Research Consortium-2 Criteria. The studied population was divided into 2 groups according to age. Out of 1336 patients, 250 (18.7%) were nonagenarians with a mean age of 91.8 ± 1.9 years.While comorbidities were less common in nonagenarians, the calculated scores to predict mortality were significantly higher. Pacemaker implantation (12.4% vs. 12.1%, P = 0.08), stroke (2% vs. 1.8%, P = 0.86) and major vascular complications (9.2% vs. 6.7%, P = 0.17) were more common in nonagenarians while acute kidney injury (1.2% vs. 2.7%, P = 0.15) and major bleeding events (3.2%vs3.4%, P = 0.87) were more common in < 90 year group. The rate of procedures success in nonagenarians and < 90 year group was 93.2% and 96.9%, respectively. Adjusted multivariate analysis showed that Nonagenarians are more likely to develop major vascular complications [OR = 1.76 95%CI (1.04;3)]. Survival analysis showed a significant difference in mortality during hospitalization period only ( P = 0.004) The prevalence of TAVI success is remarkably high in nonagenarians and comparable to that of younger age. The nonagenarians are significantly at higher risk for in-hospital death after TAVI and they are more likely to develop major vascular complications. The difference in mortality rate during hospitalization period was two times more but it becomes no longer significant after hospital discharge.

Primary endoscopic variceal ligation reduced acute variceal bleeding events but not long-term mortality in pediatric-onset portal hypertension

Esophageal variceal bleeding (EVB) is a medical emergency in patients with portal hypertension (PHT). However, studies on the long-term outcomes of prophylactic endoscopic variceal ligation (EVL) in pediatric-onset PHT are lacking. Between 1999 and 2020, patients who received EVL in the Electronic Report System of the Pediatric Endoscopy Unit were included in this retrospective study. EVL was classified as primary prophylaxis when it was performed for esophageal varices (EVs) without previous bleeding. If it was implemented in acute EVB, the subsequent EVL was classified as secondary prophylaxis. Fifty-eight patients aged 10 months to 33 years with 31 males were included. Thirty-eight patients were classified as primary prophylaxis group, and twenty, secondary prophylaxis group. The primary prophylaxis group experienced fewer 5-year EVB events than the secondary prophylaxis group (cumulative risk: 14.4% versus 32.4%). Still, it didn't significantly affect overall survival and biliary atresia transplant-free survival. Long-term mortality was significantly associated with higher serum direct bilirubin levels (≥0.55mg/dL) and lower albumin levels (≤2.54mg/dL) at the first EVL. Aspartate aminotransferase-to-platelet ratio index (APRI) with a cut-off value of 1.24 helped to predict EV presence at the initial esophagogastroduodenoscopy (EGD) (AUROC=0.762, sensitivity 75.0%, and specificity 66.7%). Primary prophylactic EVL, despite reducing acute EVB, may not change overall survival and biliary atresia transplant-free survival. APRI > 1.24 may predict EV presence at the first EGD and help to schedule a surveillance EGD. Higher direct bilirubin and lower albumin levels at the first EVL may relate to long-term mortality.

Real-World Data of the Hemostatic Efficacy of Recombinant Human Factor VIIa Eptacog Beta for Acute Bleeding Events in Patients with Hemophilia a and B with Inhibitors

Introduction: Activated prothrombin complex concentrate (FEIBA, Takeda) and recombinant factor VIIa (rFVIIa, Novoseven, NovoNordisk) remain the primary bypassing agents (BPA) available for bleeding management in patients with hemophilia and inhibitors. Eptacog beta [rFVIIa-B, Coagulation factor VIIa (recombinant)-jncw, Sevenfact, HEMA Biologics & LFB] is a recombinant human FVIIa approved by the FDA in 2020 for the treatment of acute bleeding events in adult and adolescent patients ≥12 years old with hemophilia A or B with inhibitors. rFVIIa-B demonstrated hemostatic efficacy of 86% in a phase 3, randomized cross-over study of 465 mild/moderate bleeding events in 27 patients with hemophilia A and B with inhibitors. The purpose of this study is to report real-world data on the hemostatic efficacy of rFVIIa-B for acute bleeding management in patients with hemophilia A and B with inhibitors.Methods: This is a retrospective chart-review of individuals ≥12 years of age with severe hemophilia A (factor VIII <1%) or hemophilia B (factor IX <1%) with an active inhibitor from 3 U.S. hemophilia treatment centers who utilized rFVIIa-B for acute bleed management.Results: Seven bleeds were treated among the 3 patients identified. Patient characteristics and bleeding events are summarized in Table 1. The 3 patients were 12, 13, and 31 years of age. Two patients had hemophilia A and 1 patient had hemophilia B. The 2 patients with hemophilia A were on emicizumab prophylaxis per standard dosing regimens for bleeding prevention. The individual patient with hemophilia B had a history of anaphylaxis at inhibitor development and received on-demand BPA for acute bleeding events. All 7 bleeds consisted of hemarthroses with the knee being the primary site in 57% of the bleeds. Five of the 7 bleeds (71%) received a severe bleeding dose of 210-225 microgram per kilogram (mcg/kg) for the initial rFVIIa-B dose followed by 70-75 mcg/kg for subsequent doses. Final dosing regimens were dependent on available vial sizes. rFVIIa-B resulted in complete resolution of all bleeds (100%) at a median of 4 doses (range 1-8 doses) and a median of 24 hours (range 3-48 hours). There were no failures in bleeding resolution following treatment. No adverse events with infusions were reported including infusion-related reactions, hypersensitivity reactions, thrombosis, or thrombotic microangiopathy.Conclusions: Administration of rFVIIa-B in the real-world setting appears to demonstrate hemostatic efficacy in a cohort of pediatric and adult patients with hemophilia A and B with inhibitors and may serve as an alternative human rFVIIa therapy for the management of acute bleeds in this population. Further post-marketing studies are warranted to expand the indication to younger children (<12 years of age) and to continue to monitor drug efficacy and adverse events in a larger population of patients over time including individuals on non-factor therapies such as emicizumab. [Display omitted] DisclosuresBatsuli: Bio Product Laboratory: Honoraria; Kedrion: Honoraria. Tran: HEMA Biologics: Honoraria. Young: Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Sidonio: Guardian Therapeutics: Consultancy; Octapharma: Consultancy, Research Funding; Catalyst: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding; Biomarin: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Genentech: Consultancy, Research Funding.

COVID-19 and the impact of arterial hypertension-An analysis of the international HOPE COVID-19 Registry (Italy-Spain-Germany).

BackgroundA systematic analysis of concomitant arterial hypertension in COVID‐19 patients and the impact of angiotensin‐converting‐enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID‐19 in presence and absence of arterial hypertension.Materials and MethodsOut of 5837 COVID‐19 patients, 2850 (48.8%) patients had the diagnosis arterial hypertension. 1978/2813 (70.3%) patients were already treated with ACEI or ARBs. The clinical outcome of the present subanalysis included all‐cause mortality over 40 days of follow‐up.ResultsPatients with arterial hypertension suffered significantly more from different complications including respiratory insufficiency (60.8% vs 39.5%), heart failure (9.9% vs 3.1%), acute kidney injury (25.3% vs 7.3%), pneumonia (90.6% vs 86%), sepsis (14.7% vs 7.5%), and bleeding events (3.6% vs 1.6%). The mortality rate was 29.6% in patients with concomitant arterial hypertension and 11.3% without arterial hypertension (P < .001). Invasive and non‐invasive respiratory supports were significantly more required in presence of arterial hypertension as compared without it.In the multivariate cox regression analysis, while age≥65, benzodiazepine, antidepressant at admission, elevated LDH or creatinine, respiratory insufficiency and sepsis might be a positive independent predictors of mortality, antiviral drugs, interferon treatment, ACEI or ARBs at discharge or oral anticoagulation at discharge might be an independent negative predictor of the mortality.ConclusionsThe mortality rate and in‐hospital complications might be increased in COVID‐19 patients with a concomitant history of arterial hypertension. The history of ACEI or ARBs treatments does not seem to impact the outcome of these patients.

Outcomes of activated prothrombin complex concentrate for direct Xa inhibitor bleeding

Bleeding due to oral anticoagulant therapy is recognized as a high priority drug safety problem [ [1] FDA Adverse Events Reporting System (FAERS)Latest Quarterly Data Files (2017) Food and Drug Administration Web Site. 2021 Google Scholar ]. As the use of direct Xa inhibitors continues to expand, the management of bleeding is an important issue. Andexanet, a modified human factor Xa decoy reversal agent for apixaban or rivaroxaban associated bleeding, is available in some countries however concerns with its use have been expressed [ [2] Peled H. Dau N.Q. Lau H. Key points to consider when evaluating andexxa for formulary addition. Neurocrit. Care. 2020; 33: 20-24 Crossref PubMed Scopus (7) Google Scholar ]. Four factor prothrombin complex concentrate (4FPCC) is an alternative reversal agent which has been used off-label for direct Xa inhibitor bleeding [ 3 Steffel J. et al. The 2018 european heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur. Heart J. 2018; 39: 1330-1393 Crossref PubMed Scopus (1060) Google Scholar , 4 Witt D.M. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018; 2: 3257-3291 Crossref PubMed Scopus (188) Google Scholar ]. Four factor PCC is available either as an activated or non-activated product. Limited clinical data exist evaluating activated 4FPCC, FEIBA [anti-inhibitor coagulant complex®, Baxalta US Inc., Lexington MA, USA] as a reversal agent [ 5 Engelbart J.M. et al. Safety and effectiveness of factor eight inhibitor bypassing activity for direct oral anticoagulant-related hemorrhage reversal. Am. J. Emerg. Med. 2019; 37: 214-219 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar , 6 Mao G. et al. Factor eight inhibitor bypassing agent (FEIBA) for reversal of target-specific oral anticoagulants in life-threatening intracranial bleeding. J. Emerg. Med. 2017; 52: 731-737 Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar ]. As andexanet is not on formulary, the reversal protocol at our institution recommended the use of activated 4FPCC 25–50 IU/kg for direct Xa inhibitor bleeding for situations where reversal is desired. Our goal was to assess the patient characteristics, management and outcomes of activated 4FPCC for reversal of apixaban or rivaroxaban acute bleeding events.

Activated prothrombin complex concentrate for reversal of oral factor Xa inhibitors at a level 1 trauma center

Direct oral anticoagulants (DOACs) are associated with fewer bleeding complications compared to warfarin (Coumadin®, Manati, Puerto Rico), specifically intracranial hemorrhage (ICH), however reversal in the setting of a life-threatening bleed may be required [1,2]. Treatment options for factor Xa inhibitors include andexanet alfa (Andexxa®, San Francisco, California, United States), prothrombin complex concentrate (PCC), and activated PCC (aPCC). These medications are recommended by supporting guidelines for treatment of oral factor Xa inhibitor-related acute major bleeding events, including ICH [3,4].

Ethical Decision Making Framework in Previously Untreated Severe Hemophilia A Patients

Treatment recommendations and decision making for severe hemophilia A previously untreated patients (PUPs) have recently become a significant debate with an ethical valence. Primary prophylaxis, initiation of factor replacement prior to the second joint bleed and before the age of three, has been the recommended standard of care in resource rich countries for the last two decades. Since the widespread availability of recombinant factor VIII (rFVIII) products, the choice has been fairly straightforward for PUPs, whereby transmission of blood borne pathogens associated with plasma-derived FVIII (pdFVIII) products were avoided. The Survey of Inhibitors in Plasma-Products Exposed Toddlers (SIPPET) randomized controlled trial demonstrated a higher incidence of FVIII alloantibody inhibitors in PUPs started on rFVIII products compared to pdFVIII products (Peyvandi F, et al., 2016). This finding has had a tremendous controversial impact on the decision making of product choice for PUPs despite the supportive Medical and Scientific Advisory Council recommendations to consider starting a PUP on a pdFVIII product (MASAC, 2016).For this patient population, we developed a modified utilitarian framework of decision making that employs clinical, public health, and research ethics. The framework recognizes that there are many stakeholders involved in the provision of FVIII products and health care of those with severe hemophilia A and provides guidance when there is concern for bias. Utilizing the premise of shared decision making, the framework takes a patient and family centered rather than a paternalistic approach. In discussions about care, it is recommended that the provider learn about relevant patient and family values. Doing so would better enable providers to inform the patient and family about the available treatments (including the risks, benefits and alternatives) and disclose any conflicts of interest and biases. Using shared decision making would serve to maximize understanding, minimize bias, respect informed consent or dissent, and provide care that aligns with patient values when medically and practically feasible.The framework has three tiers. First, it evaluates whether resources are scarce or abundant, which is important in equitably allocating resources. Where life-saving FVIII products are scarce, there could be a direct impact on patient care and clinical research. Healthcare providers would be at risk of compromising not only standard of care but also their fiduciary responsibilities to patient care in bedside rationing. If FVIII products are scarce, we recommend developing a central supply for emergency use and then evaluating the needs of the severe hemophilia A patients. Prioritization of who receives the factor products would be decided by a designated team based on the availability of the factor products and clinical scenarios, with no preference given to those on research trials. However, if resources are abundant, treatment for acute bleeding and standard of care prophylaxis measures, including primary prophylaxis, could continue.The second tier takes into account whether there is a new infectious epidemic or concern where the pathogen cannot be eliminated. If not, pdFVIII and rFVIII products are to be equally presented. If there is an epidemic, healthcare and public health workers may limit the use of pdFVIII products.The third tier evaluates the clinical scenario and if there is an acute bleeding emergency or not. If there is an acute bleeding event, the immediately available resource should be recommended, along with bypassing and/or adjuvant resources as needed until the bleeding has resolved or improved. To align with patient and family preferences, attempts to have both pdFVIII and rFVIII products available at similar costs in institutions would be ideal.The ethical framework we developed endeavors to balance autonomy, beneficence, nonmaleficence and justice. As treatment decisions are complex, the framework may help guide discussions among providers, PUPs with severe hemophilia A, and their families.Disclaimer:The findings and conclusions in this abstract are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention, Emory University, or Children's Healthcare of Atlanta. DisclosuresSidonio:Bioverativ: Consultancy; CSL Behring: Consultancy; Grifols: Research Funding; Bioverativ: Research Funding; Shire: Consultancy, Research Funding; Novo Nordisk: Consultancy; Bayer: Consultancy.

Major Bleeding and Bleeding Events Requiring Hospitalization in the First Three Months Following Vitamin K Antagonists Therapy in Patients with First Venous Thromboembolism

Introduction: The management of venous thromboembolism (VTE) and the prevention of recurrent VTE consists of anticoagulation primarily with Vitamin K Antagonists (VKA). The main adverse effect of anticoagulation is bleeding. This study aimed to investigate the incidence and established and new predictors of significant bleeding occurring in primary care within 3 months after treatment initiation with VKA in patients with first VTE.Methods: A cohort study was undertaken using the United Kingdom's primary care Clinical Practice Research Datalink with additional data from hospitalizations and causes of death. Patients with incident first VTE between January 2008 and March 2016 treated with VKA within 60 days after first VTE, were included in the cohort. Bleeding was defined as and either major bleeding or clinically relevant non-major bleeding requiring hospitalisation (CRNMB) in accordance with the International Society of Thrombosis and Haemostasis recommendations. Major bleeding and CRNMB events were reviewed, adjudicated, and validated by physicians experienced in care of VTE patients. Bleeding events that occurred in the hospital setting were excluded. Patients were followed for three months from VKA treatment initiation. Sub-hazard ratios (SHR) were estimated from Fine-Gray regression models with mortality as a competing risk and time-dependent covariates. Models included recognized predictors for major bleeding and CRNMB before the diagnosis of VTE and a list of potential predictors during VKA treatment.Results: Among 11,871 VKA-treated VTE patients there were 45 community-acquired acute major bleeding events and 146 CRNMB events requiring hospitalization in the first 3 months following commencement of VKA therapy. The three month cumulative incidence of community-acquired major bleeding and CRNMB was 0.4% and 1.3% respectively. Incidence rates for each type of bleeding peaked in the first two weeks after the start of VKA therapy. Independent predictors for major bleeding included male sex, adjusted SHR 1.92 (95%-confidence interval: 1.06-3.57), anaemia within 6 months before first VTE 2.50 (1.24-5.03), history of renal disease 2.16 (1.04-4.46), and trauma during VKA treatment 18.8 (6.39-55.1) (Table 1). Independent predictors for CRNMB included male sex 1.59 (1.12-2.22), active cancer 3.21 (2.10-4.93), trauma during VKA treatment 3.07 (1.08-8.75), history of dementia 2.47 (1.13-5.39) and history of CRNMB 1.73 (1.23-2.43) (Table 2).Conclusions: Clinically relevant non-major bleeding requiring hospitalization occurred at least three times as often as major bleeding. Event rates are highest in the initial period following commencement of VKA therapy. Assessment for and awareness of predictors prior to and during VKA treatment are needed to prevent significant bleeding events. Caution is warranted early after commencing VKA, particularly in patients with prevalent risk factors. [Display omitted] DisclosuresMartinez:CSL Behrig: Research Funding; Bayer AG: Research Funding; Bristol-Myers Squibb: Research Funding; Merz Pharma: Research Funding. Cohen:Portola: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Katholing:Institute for Epidemiology, Statistics and Informatics GmbH: Employment. Wallenhorst:Institute for Epidemiology, Statistics and Informatics GmbH: Employment. Li:Bristol-Myers Squibb: Employment, Equity Ownership. Wygant:Bristol-Myers Squibb: Employment, Equity Ownership; University of Delaware School of Nursing Advisory Committee: Membership on an entity's Board of Directors or advisory committees.

Role of Hysterectomy in Gestational Trophoblastic Neoplasia.

Hysterectomy has a limited role in the management of gestational trophoblastic neoplasia because of the high effectiveness of chemotherapy and the young age of patients. In selected patients, it is believed to help in reducing the number of chemotherapy cycles, overcoming chemo-resistance, and treating acute haemorrhagic events. The present study aimed to evaluate the indications and outcomes of hysterectomy in patients with GTN at a tertiary care centre in India. Between 2012 and 2019, we identified all patients with GTN from the hospital database. Demographic, clinical, and follow-up details of patients who underwent hysterectomy were obtained from the electronic medical records. During the study period, 98 cases of GTN were treated at our centre of which 54% were low-risk and 46% were high-risk cases. Twenty-six patients (26%) underwent hysterectomy as part of their management for GTN. The patients belonging to the high-risk group had more hysterectomies (65%) with an odds ratio of 2.96. The common pathological diagnosis was choriocarcinoma in 44% and an invasive mole in 30% of patients. Bleeding, either intraperitoneal or vaginal, was the most common indication for hysterectomy (48%). The median number of chemotherapy cycles received was 5 in patients who had primary hysterectomy and 6 in patients who did not have hysterectomy. The majority of patients received EMACO (57.7%) chemotherapy. The mean duration of follow-up was 18months (range 1-67).After treatment, complete remission was achieved in 94 out of 98 (95.9%) and also in all patients (100%) who had undergone hysterectomy as adjuvant procedure. Three patients died during treatment (3.06%), all belonging to the high-risk group, and one patient had a recurrence (0.01%). In selected cases of GTN, hysterectomy may be an effective means to reduce or eliminate tumour bulk, to overcome chemoresistance and manage acute bleeding events.

Impact of the COVID-19 Pandemic on Acute Upper Gastrointestinal Bleeding in Xingtai City.

Background and Aims The coronavirus disease 2019 (COVID-19) has severely impacted the daily practice of gastrointestinal endoscopy worldwide. Most endoscopy centers in China were shut down in late January 2020. We investigated the impact of the shutdown on acute upper gastrointestinal bleeding (AUGIB) events in Xingtai City, Hebei Province, China. Methods A web-based survey collected information on gastroscopy workload and AUGIB events. The study period was from 4 weeks before to 4 weeks after lockdown initiation in Xingtai City. Fourteen public gastrointestinal endoscopy centers performing emergency endoscopies were contacted via e-mail to collect weekly emergency gastroscopy volumes and the number of AUGIB events. AUGIB was defined as recent melena, hematemesis, or both, with an endoscopically visible source of bleeding. Results Twelve (85.7%) of the 14 surveyed gastrointestinal endoscopy centers in the city- and county-level hospitals responded. Altogether, 4,045 and 1,077 gastroscopy procedures were performed 4 weeks before and after lockdown initiation (73.4% reduction), respectively. Peptic ulcer-related AUGIB and variceal AUGIB events showed a 58.5% and 52.9% decline, respectively, compared with pre-COVID-19 data. Although the absolute number of AUGIB events decreased during the pandemic (from 149 to 66), the likelihood of detecting AUGIB during gastroscopy increased (3.68% (pre-COVID-19 period) versus 6.13% (COVID-19 period); P < 0.05). Conclusion The COVID-19 pandemic resulted in a considerable reduction in gastroscopy workload and AUGIB events; however, the likelihood of detecting AUGIB increased significantly during gastroscopies.

Time to four‐factor prothrombin complex concentrate administration decreased by presence of a 24/7 pharmacist in the emergency department

AbstractStudy objectiveThe objective of this study was to determine the impact of a 24/7 pharmacist (RPh) on time from order to the administration of four‐factor prothrombin concentrate complex (4F‐PCC) in the emergency department (ED).MethodsThis is a retrospective study that included patients who received 4F‐PCC in the ED for acute reversal of oral anticoagulation before and after the implementation of a 24/7 RPh. Patients for whom 4F‐PCC was ordered between May 1, 2014 and June 30, 2015 were in the pre‐RPh group and those between November 1, 2018 and December 31, 2019 were in the post‐RPh group. The primary end point was time from order to administration of 4F‐PCC. Time from arrival to administration of 4F‐PCC was also evaluated.ResultsOf 168 patients evaluated, 100 were included in the study (n = 33 pre‐RPh; n = 67 post‐RPh). The majority of patients were on warfarin (97.0% pre‐RPh and 73.1% post‐RPh) for atrial fibrillation. Both groups included trauma and intracranial hemorrhage patients. The mean time from order to 4F‐PCC administration was significantly shorter in the post‐RPh group (71.2 vs 35.2 minutes, P &lt; .001, 95% confidence interval [CI] [27.013‐44.987]). In addition, the median time from arrival to 4F‐PCC administration was also shorter in the post‐RPh group (153 vs 106 minutes, P = .033).ConclusionsAt our institution, time from order, and from arrival, to administration of 4F‐PCC for reversal of oral anticoagulation in the setting of acute bleeding events in the ED was reduced by 36 minutes after the presence of a 24/7 pharmacist.

A Multicenter Prospective Observational Cohort Study to Investigate the Effectiveness and Safety of Rivaroxaban in Japanese Venous Thromboembolism Patients (The J'xactly Study).

There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban. In this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events. In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.

Long-Term Imaging Evolution and Clinical Prognosis Among Patients With Acute Penetrating Aortic Ulcers: A Retrospective Observational Study.

BackgroundAcute penetrating aortic ulcers (PAUs) are reported to dynamically evolve into different clinical outcomes ranging from regression to aortic rupture, but no practice guidelines are available in China.Methods and ResultsAll 109 patients with acute PAUs were monitored clinically. At 30 days follow‐up, 31 patients (28.44%) suffered from aortic‐related adverse events, a composite of aortic‐related mortality, aortic dissection, or an enlarged ulcer. In addition, 7 (6.42%) patients had clinically related adverse events, including all‐cause mortality, cerebral stroke, nonfatal myocardial infarction, acute heart failure alone or acute exacerbation of chronic heart failure, acute renal failure, arrhythmia, and bleeding events. In the present study, the intervention criteria for the Chinese PAU population included a PAU diameter of 12.5 mm and depth of 9.5 mm. The multivariate analysis showed that an ulcer diameter >12.5 mm (hazard ratio [HR], 3.846; 95% CI, 1.561–9.476; P=0.003) and an ulcer depth >9.5 mm (HR, 3.359; 95% CI, 1.505–7.494; P=0.003) were each independent predictors of aortic‐related events.ConclusionsPatients with acute PAUs were at high risk for aortic‐related adverse events and clinically related adverse events within 30 days after onset. Patients with an ulcer diameter >12.5 mm or an ulcer depth >9.5 mm have a higher risk for disease progression, and early intervention may be recommended.

Spontaneous neck hematoma secondary to parathyroid adenoma: a case series.

Spontaneous neck hematoma is a rare yet potentially fatal complication of primary hyperparathyroidism (PHPT). Herewe aim to describe novel presentations of neck hematomas secondary to PHPT, discussing tools and signs that facilitate diagnosis. Case series data were extracted by retrospective chart reviews of our institution's electronic medical records, including all neck hematoma cases from parathyroid origin between 2005 and 2020. Cases from PubMed and EMBASE between 1999 and 2020 were analyzed in a systematic literature review. Four patients were identified with five acute bleeding events, including a novel report of recurrent neck hemorrhage due to parathyroid adenoma. There was postmenopausal female predominance (75%), consistent with previous reports (72.7%). Common presentations included neck pain, dysphagia and hoarseness. All bleedings spread into the retropharyngeal space. Vocal cord paralysis was found in a single case and in 8.6% of the benign lesions in the reviewed cases. A single case presented with normal calcium levels (20% of bleeding episodes), in line with the reviewed cases (17.4%). A subtle CT sign of an enhancing area within the parathyroid gland, which led to the diagnosis, was identified in a single case. Conservative treatments were employed in 80% of our cases and in 51.5% of the reviewed cases, all being successful. Neck explorations performed after a 3-month waiting period from the acute event demonstrated better results compared to immediate surgery. A high suspicion index is needed, particularly in post-menopausal women, to reach a diagnosis and allow optimal management. Normal laboratory values do not exclude parathyroid etiology, yet assessment should include calcium and PTH levels along with targeted imaging. Since bleeding may recur, we suggest that PHPT complicated with neck hematoma should be anindependent indication for definitive parathyroidectomy surgery. 3b.

Severe Bleeding Events in Hemophilia Α Patients Receiving Emicizumab Prophylaxis

Severe Bleeding Events in Hemophilia Α Patients Receiving Emicizumab Prophylaxis

Fitusiran, an RNAi Therapeutic Targeting Antithrombin to Restore Hemostatic Balance in Patients with Hemophilia a or B with or without Inhibitors: Management of Acute Bleeding Events

Background Fitusiran is a once-monthly subcutaneously administered investigational RNA interference (RNAi) therapeutic targeting antithrombin (AT) to enhance thrombin generation (TG) and rebalance hemostasis in patients with hemophilia A (HA) or hemophilia B (HB) with or without inhibitors. Phase 1 and 2 data show dose-dependent lowering of AT, increased TG, and a decrease in the frequency of spontaneous and traumatic bleeds on fitusiran. Given AT knockdown with fitusiran, bleed management guidelines supporting the use of low-dose and reduced-frequency factor or bypassing agent (BPA) were developed and implemented to manage breakthrough bleeds in subjects participating in clinical trials of fitusiran (Table 1). Aim To report the available results on the management of breakthrough bleeding events in subjects on prophylactic therapy with fitusiran using low-dose and reduced-frequency factor or BPA. Methods The ongoing Phase 2 study includes subjects with HA or HB with or without inhibitors who were previously exposed to fitusiran in the Phase 1 study. Subjects received monthly fixed doses of fitusiran 50 mg or 80 mg subcutaneously. To assess the effectiveness of the bleed management guidelines, analyses of 11 months of available data on breakthrough bleeds and treatment after the implementation of the guidelines were performed. Presented are data from an interim ad hoc analysis of a Phase 2 open-label extension study. Results Of the 26 subjects included in this study population, 20 have HA (with inhibitors, n=10; without inhibitors, n=10) and 6 have HB (with inhibitors, n=2; without inhibitors, n=4). Fifteen subjects had ≥1 bleed and 12 subjects (80%) were compliant with the bleed management guidelines. A total of 107 bleeding events evaluable for compliance with the guidelines at the time of data cutoff in 14 subjects required treatment with factor or BPA. A single reduced dose of factor or BPA was sufficient to manage 62 of 107 bleeds (60%) requiring treatment (HA with inhibitors, 21 of 27 bleeds [78%]; HA without inhibitors, 23 of 25 bleeds [92%]; HB with inhibitors, 17 of 51 bleeds [33%]; HB without inhibitors, 1 of 4 bleeds [25%]). Of the 28 bleeds in 5 subjects requiring repeat dosing, 15 (54%) were treated according to the recommended dose and frequency of factor or BPA (HA with inhibitors, 1 of 5 bleeds [20%]; HA without inhibitors, 2 of 2 bleeds [100%]; HB with inhibitors, 9 of 18 bleeds [50%]; HB without inhibitors, 3 of 3 bleeds [100%]). Updated data reflecting additional (≥9 months) exposure to fitusiran will be presented at the time of the meeting. Conclusions Bleed management guidelines were implemented to support the management of breakthrough bleeding events in subjects on prophylactic therapy with fitusiran. Since implementation of the bleed management guidelines, all treated bleeding events in subjects with HA or HB with or without inhibitors have been successfully managed with factor or BPA, and most have been managed using reduced and less frequent dosing of factor or BPA in accordance with the guidelines. Study funded by Alnylam and Sanofi. Disclosures Pipe: Spark Therapeutics: Consultancy; Freeline: Consultancy; Shire: Consultancy; BioMarin: Consultancy; HEMA Biologics: Consultancy; Sanofi: Consultancy; Bayer: Consultancy; Catalyst Bioscience: Consultancy; Novo Nordisk: Consultancy; uniQure: Consultancy; CSL Behring: Consultancy; Roche/Genentech: Consultancy; Pfizer: Consultancy; Apcintex: Consultancy. Ragni:Spark Therapeutics: Other: Advisory Board, Research Funding; Sangamo: Research Funding; Alnylam/Sanofi: Other: Advisory Board, Research Funding; BioMarin: Other: Advisory Board, Research Funding; Bioverativ/Sanofi: Other: Advisory Board, Research Funding; OPKO: Research Funding; Shire/Takeda: Other: Advisory Board, Research Funding. Négrier:Shire/Takeda: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding, Speakers Bureau; Spark Therapeutics: Honoraria, Research Funding, Speakers Bureau; Alnylam (Sanofi): Honoraria, Speakers Bureau; Sobi: Honoraria, Research Funding, Speakers Bureau; Freeline: Research Funding; LFB (laboratoire français du fractionnement et des biotechnologies): Research Funding; Novo Nordisk: Honoraria, Research Funding, Speakers Bureau; Octapharma: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Patents: Patents &amp; Royalties: Patents related to FVIII and FIX; Catalyst Biosciences: Honoraria, Speakers Bureau; Bayer: Consultancy, Research Funding. Yu:Sanofi: Employment. Bajwa:Sanofi: Employment. Caminis:Sanofi: Employment. Mei:Sanofi: Employment. Andersson:Sanofi: Employment.

Cardiovascular Risk Factors and Secondary Events Among Acute and Chronic Stable Myocardial Infarction Patients: Findings from a Managed Care Database.

IntroductionLong-term risk for recurrent cardiovascular events among myocardial infarction (MI) patients in the acute versus chronic stable phase is not well characterized. This study was conducted to evaluate risk factors associated with all-cause mortality and cardiovascular (CVD) morbidity and to determine the transition period from the acute to chronic stable phase of disease.MethodsAdministrative claims data from a managed care database (2007–2012) were linked to the Social Security Death Index. Kaplan–Meier curves were generated over a 3-year period. The association between risk factors and clinical endpoints was assessed using Cox proportional hazard models. Poisson models estimated the ‘transition time’ from acute to chronic phase of disease.ResultsOn average, recurrent cardiovascular event rates were higher among acute MI patients in comparison to the chronic MI patients during the first 3 months of follow-up. Over the 3-year follow-up period, survival curves became parallel and for some outcomes (i.e., acute myocardial infarction and bleeding events), were not statistically significantly different between the two groups. In both the acute and chronic MI cohorts, diabetes, heart failure, and renal disease were consistently statistically significant and positively associated with greater risk of death and ischemic events. PAD was consistently associated with increased risk among the chronic cohort and composite endpoints among the acute patients.ConclusionsGreater understanding of differences in the CVD risk profiles and the transition from acute to chronic stable phase may help identify high-risk patients and inform clinical risk stratification and long-term disease management in MI patients.FundingMerck & Co., Inc., Kenilworth, NJ, USA.Electronic supplementary materialThe online version of this article (10.1007/s40119-019-00147-5) contains supplementary material, which is available to authorized users.

Accuracy of ICD-10 codes for identifying hospitalizations for acute anticoagulation therapy-related bleeding events

IntroductionAdministratively coded data are frequently used in observational research to identify outcome events. With the transition to the new International Classification of Diseases coding system's 10th version (ICD-10), information is needed about the coding accuracy for bleeding events in anticoagulated patients. We aimed to determine ICD-10 code accuracy for bleeding events in anticoagulated patients admitted to the hospital. MethodsThis cross-sectional study retrospectively examined charts of anticoagulated patients who were admitted to the University of Utah Hospital between October 1, 2017 and December 31, 2017. Two trained chart abstractors blinded to ICD-10 code status independently reviewed medical charts to determine the presence or absence of bleeding events. ICD-10 code status in any diagnosis position was unblinded and code accuracy was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) along with 95% confidence intervals (CI). ResultsOut of 661 admissions, 487 unique patients and 71 bleeding events were identified. Gastrointestinal tract bleeding and intracranial hemorrhage comprised 32.4% and 19.7% of bleeding events respectively. ICD-10 code sensitivity was 91.4% (95% CI, 82.3–96.8), specificity was 90.2% (87.5–92.5), PPV was 52.5% (43.2–61.6) and NPV 98.9% (97.6–99.6). Individual codes for intracranial hemorrhages and gastrointestinal tract bleeding had similar accuracy as the overall set of bleeding codes. ConclusionsOur results demonstrate that ICD-10 codes can reliably rule-out hospitalizations for bleeding events in patients receiving anticoagulation therapy. Due to unacceptable false positive rates ICD-10 codes should not be used for identifying bleeding complications without confirmatory chart review.

Esophageal variceal bleeding: management and tips on transjugular intrahepatic portosystemic shunt

Esophageal variceal bleeding is a life-threatening complication in patients with liver cirrhosis, which is pathophysiologically explained by the presence of portal hypertension. The incidence of such bleeding greatly depends on the severity of the underlying liver disease. The aim of this article is to present the current treatment concepts for acute esophageal variceal bleeding, the management in acute situations and the indications for treatment of the causal portal hypertension with a transjugular intrahepatic portosystemic shunt (TIPS). In patients with liver cirrhosis or any other disease causing portal hypertension, a staging examination by esophagogastroduodenoscopy is first carried out for determination of the stage of the varices and the resulting necessary treatment. In addition, determination of the portal pressure gradient is useful. In patients with varices amedicinal or endoscopic bleeding prophylaxis should subsequently additionally be initiated. After an acute variceal bleeding event, under clearly defined prerequisites an evaluation for TIPS implantation should be considered. This is the only effective treatment for reducing portal hypertension. With appropriate indications implantation of a TIPS is an effective strategy to lower portal hypertension and therefore prevent recurrent variceal bleeding. The resulting improvement of the portal hemodynamics leads to an improvement in kidney function; however, it also leads to deterioration of liver function with subsequent development or deterioration of a previously existing hepatic encephalopathy.