Risk Of Severe Bleeding Research Articles

The Association between Factor XI Deficiency and the Risk of Bleeding, Cardiovascular, and Venous Thromboembolic Events.

The objective of this study was to assess the relationship between factor XI (FXI) deficiency and the risks of bleeding and cardiovascular (CV) events. We conducted a retrospective cohort study using data from Maccabi Healthcare Services (MHS). We identified adults with FXI deficiency (severe: <15%, partial: 15 to <50%, any deficiency: <50%) that had been tested for FXI between 2007 and 2018 and matched to patients from the general MHS population. We estimated 10-year risks of outcomes using the Kaplan–Meier approach. Using Cox proportional hazards regression, we compared outcomes among patients with versus without FXI deficiency. Less than 10% of patients tested for FXI activity had activity levels <50% (mean age: 39 years; 72.2% females). Compared with the general population, patients with any FXI deficiency were at higher risk of severe bleeding (adjusted hazard ratio [aHR]: 2.56, 95% confidence interval [CI]: 1.13–5.81; 10-year risk: 1.90%, 95% CI: 0.50–3.20% vs. 0.90%, 95% CI: 0.50–1.30%) and clinically relevant nonsevere bleeding (CRNSB) (aHR: 1.45, 95% CI: 1.08–1.97; 10-year risk: 11.60%, 95% CI: 8.30–14.80% vs. 9.20%, 95% CI: 8.00–10.40%). Severe FXI deficiency was associated with a greater risk of CRNSB. While few CV events ( N = 2) and venous thromboembolisms (VTE) ( N = 1) were observed in the FXI overall deficient group, there was a nonsignificant negative association between any FXI deficiency and CV events (aHR: 0.55; 95% CI: 0.13–2.36) and VTEs (aHR: 0.45; 95% CI: 0.06–3.47). Overall FXI deficiency was associated with an increased risk of severe bleeding and CRNSB. Further research is warranted to explore the lower risk of CV and VTE among patients with FXI deficiency compared with the general population.

Hematologic Autoimmune Manifestation Secondary to Coronavirus Disease 19 Infection – A Single-Center Experience

Introduction: Since December 2019, multiple human cases of novel coronavirus infection were reported, representing with upper respiratory symptoms (influenza-like presentation). The virus was named the Severe acute respiratory system coronavirus 2 (SARS-COV-2). Studies have reported cases of patients with COVID-19 infection, including development of several autoimmune events that suggests that infection with SARS CoV-2 may be associated with initiation of autoimmune hematological autoimmune disorders.&#x0D; Aim: Review the hematological autoimmune phenomenon after infection with SARS-COV-2 in order to assist into the pathogenic mechanisms, clinical manifestations and treatment of this group of patients. &#x0D; Materials and methods: This is a retrospective study that includes 21 patients with autoimmune diseases like secondary immune thrombocytopenia (ITP), autoimmune hemolytic anemia( AIHA) and thrombotic thrombocytopenic purpura (TTP) that have emerged after COVID-19 infection. The patients were diagnosed and treated at the University Clinic of Hematology for a period of time from January 2020 to April 2021.&#x0D; Results: The most common hematologic autoimmune disorder was ITP in 13 cases (62%) followed by AIHA in 5 cases (24%) and TTP in 3 individuals (14%). The mean time of onset of the hematologic auto-immune presentations was 18,4 ± 10,3 days. The therapy of this conditions in patients with COVID-19 infection requires an individualized approach to achieve a precise balance between the risk of severe bleeding and of thromboembolic events. &#x0D; Conclusion: Causal relationship between COVID-19 infection and these autoimmune events still requires further studies. We should all have in mind the risk of development of hematologic autoimmune disorders in infected patients.

Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

P2Y12 receptor inhibitor plus aspirin versus aspirin treated within 24 hours of acute noncardioembolic ischemic stroke or TIA: Meta-analysis

Antiplatelet therapy is the cornerstone for acute ischemic stroke or transient ischemic attack (TIA). The purpose of this study was to conduct a meta-analysis to assess the efficacy and safety of P2Y12 receptor inhibitor plus aspirin versus aspirin alone treated within 24h after acute noncardioembolic ischemic stroke or TIA. We search Pubmed, EMBASE, CENTRAL and clinicaltrials.gov from January 1966 to January 2021. We included randomized trials which compared P2Y12 receptor inhibitor plus aspirin versus aspirin alone. Relative risk (RR) with 95% confidence (CI) was used as a measure of P2Y12 receptor inhibitor plus aspirin versus aspirin. The primary efficacy endpoint was recurrent stroke and the primary safety endpoint was severe bleeding. The search identified 5 randomized trials comparing P2Y12 receptor inhibitor plus aspirin and aspirin with 21,808 individuals enrolled. Pooled results from these trials showed that P2Y12 receptor inhibitor plus aspirin compared with aspirin was associated with a lower risk of recurrent stroke (RR 0.75, 95% CI 0.68 to 0.83). Ticagrelor plus aspirin compared with aspirin was associated with increased risk of severe bleeding (RR 3.98, 95% CI 1.74 to 9.10) and intracranial hemorrhage (RR 3.32, 95% CI 1.33 to 8.25), whereas clopidogrel plus aspirin vs. aspirin had similar hemorrhagic risk. P2Y12 receptor inhibitor plus aspirin vs aspirin given within 24h after acute noncardioembolic ischemic stroke or TIA reduces the risk of subsequent stroke. However, the risk of severe bleeding, including intracranial hemorrhage, was higher with ticagrelor plus aspirin vs aspirin. CRD42020203730.

Frequency and risk factors of severe postoperative bleeding after proctological surgery: a retrospective case-control study.

The aim of this study was to assess frequency and risk factors of severe bleeding after proctological surgery requiring hemostatic surgery observed after publication of the French guidelines for anticoagulant and platelet-inhibitor treatment. All patients who underwent proctological surgery between January 2012 and March 2017 in a referral center were included. Delay, severity of bleeding, and need for blood transfusion were recorded. Patients with severe postoperative bleeding were matched to controls at a 2:1 ratio adjusted on the operator, and the type of surgery. Among the 8,890 operated patients, 65 (0.7%) needed a postoperative hemostatic procedure in an operating room. The risk of a hemostatic surgery was significantly increased after hemorrhoidal surgery compared with other procedures (1.9% vs. 0.5%, P<10-4) and was most frequent after Milligan-Morgan hemorrhoidectomy (2.5%). Mean bleeding time was 6.2 days and no bleeding occurred after day 15. Blood transfusion rate was 0.1%. Treatment with anticoagulants and platelet inhibitors were managed according to recommendations and did not increase the severity of bleeding. The risk of severe bleeding was significantly lower in active smokers vs. non-smokers in univariate (16.9% vs. 36.2%, P=0.007) and multivariate (odds ratio, 0.31; 95% confidence interval, 0.14-0.65) analysis whereas sex, age, and body mass were not significantly associated with bleeding. Severe postoperative bleeding occurs in 0.7% of patients, but varies with type of procedure and is not affected by anticoagulant or antiplatelet treatment. These treatments given in accordance with the new guidelines do not increase the severity of postoperative bleeding.

Meta-Analysis of Usefulness of Antiplatelet Therapy in Ischemic Stroke or Transient Ischemic Attack

The efficacy of early administration of dual antiplatelet therapy (DAPT) for secondary prevention after acute ischemic stroke or transient ischemic attack (TIA) is uncertain. This systematic review and meta-analysis compares the safety and efficacy of early administration (<24 hours) of DAPT (using either clopidogrel or ticagrelor with aspirin) versus single antiplatelet therapy (SAPT; aspirin alone) in acute non-cardioembolic ischemic stroke or TIA, incorporating data from large randomized controlled trials. Published trials fulfilling our criteria were identified from an electronic search of MEDLINE, with key words including: "clopidogrel or ticagrelor", "aspirin", "ischemic stroke", "transient ischemic attack", and "randomized controlled trial". Included were 3 randomized controlled trials of 21,067 patients assessing early administration (<24 hours from symptom onset) of DAPT versus SAPT in non-cardioembolic acute ischemic stroke or TIA. Our efficacy outcomes were ischemic stroke and all-cause mortality. Our safety outcome was severe bleeding. We performed a meta-analysis to pool results with a hierarchical Bayesian random-effects model. Dual antiplatelet therapy significantly reduced the risk of ischemic stroke (hazard ratio [HR], 0.73; 95% credible interval [CrI]: 0.54, 0.97), while increasing the risk of severe bleeding (HR, 2.48; 95% CrI: 1.07, 5.26). There was a non-significant numerical trend toward increased mortality with DAPT (HR, 1.29; 95% CrI: 0.73, 2.23). These observations were robust under the sensitivity analysis. In the present systematic review and meta-analysis of randomized controlled trials, DAPT reduced the risk of ischemic stroke at the cost of an increase in severe bleeding. Additional trials examining the ideal timing of DAPT administration are needed to thoroughly investigate the role, if any, of routine DAPT in patients with non-cardioembolic ischemic stroke or high-risk TIA.

Severe bleeding following off-pump coronary artery bypass grafting: predictive factors and risk model.

BACKGROUNDSevere bleeding following cardiac surgery remains a troublesome complication, but to date, there is a lack of comprehensive predictive models for the risk of severe bleeding following off-pump coronary artery bypass grafting (OPCABG). This study aims to analyze relevant indicators of severe bleeding after isolated OPCABG and establish a corresponding risk assessment model.METHODSThe clinical data of 584 patients who underwent OPCABG from January 2018 to April 2020 were retrospectively analyzed. We gathered the preoperative baseline data and postoperative data immediately after intensive care unit admission and used multifactor logistic regression to screen the potential predictors of severe bleeding, upon which we established a predictive model. Using the consistency index and calibration curve, decision curve, and clinical impact curve analysis, we evaluated the performance of the model.RESULTSThis study is the first to establish a risk assessment and prediction model for severe bleeding following isolated OPCABG. Eight independent risk factors were identified: male sex, aspirin/clopidogrel withdrawal time, platelet count, fibrinogen level, C-reactive protein, serum creatinine, and total bilirubin. Among the 483 patients in the training group, 138 patients (28.6%) had severe bleeding; among the 101 patients in the verification group, 25 patients (24.8%) had severe bleeding. Receiver operating characteristic (ROC) curve analysis for the internal training group revealed a convincing performance with a concordance index (C-index) of 0.859, while the area under the ROC curve for the external validation data was 0.807. Decision curve analysis showed that the model was useful for both groups.CONCLUSIONSAlthough there are some limitations, the model can effectively predict the probability of severe bleeding following isolated OPCABG and is therefore worthy of further exploration and verification.

Risk Factors for Bleeding, Including Platelet Count Threshold, in Newly Diagnosed ITP Patients

Introduction: Bleeding is a main cause of morbidity and mortality in adult immune thrombocytopenia (ITP). Treatment is indicated in case of bleeding or of low platelet count. However, the threshold of platelet count associated with bleeding and therefore to initiation of treatment is debated. Most of guidelines recommend the threshold of <30 x 109/L. However, some authors recommend other thresholds, as low as 10 x 109/L. Moreover, the risk factors for bleeding are not well known in ITP. The aim of this study is to assess the risk of bleeding by platelet count and to identify these risk factors.Methods: We studied all the patients included between June 2013 and December 2016 in the CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry. This multicenter registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants). Each investigator follows every patient newly diagnosed for ITP in routine visit or hospital stay and detailed information on patients' characteristics and management of ITP are recorded prospectively. We also included all adult patients newly diagnosed for ITP at the French National Referral Center for autoimmune cytopenias (Créteil) from November 2015 to December 2016 where data are prospectively recorded in the same database. ITP was defined by platelet count <100 x 109/L and exclusion of other causes of thrombocytopenia. We described the frequency of any bleeding, of mucosal bleeding and of severe bleeding (defined by macroscopic hematuria, gastrointestinal or central nervous system bleedings) at ITP onset by platelet count and by subgroups of interest: age groups (according to quartiles: ≤45, 45-64, 65-79 and ≥80 years), sex, arterial hypertension, history or current symptoms of gastroduodenal ulcer, Charlson's comorbidity score, exposure to non-steroidal anti-inflammatory drugs (NSAIDs), antiplatelet drugs, anticoagulant drugs and serotonin reuptake inhibitors (SRIs). Lastly, we assessed in the whole cohort the factors associated with any bleeding, mucosal bleeding and severe bleeding using multivariate logistic regression analysis.Results: 302 newly diagnosed ITP adults were prospectively included in the study. Median age was 66 years, 49.7% were females, 46.8% had a Charlson's score ≥1, 3.7% had a history or current symptoms of gastroduodenal ulcer, 16.0% had secondary ITP, 19.5% were exposed to antiplatelet drugs, 7.6% to anticoagulant drugs, 7.6% to NSAIDs and 6.6 to SRIs at the time of diagnosis. Median platelet count was 18 x109/L. At diagnosis, 57.9% experienced any bleeding symptom, 30.1% mucosal bleeding, and 6.6% severe bleeding (including 4 central nervous system bleedings).The rates of bleeding, mucosal bleeding and severe bleeding by platelet count is shown in Figure 1. The rate of any bleeding was >50% if platelet count was <20 x109/L. The rate of mucosal bleeding was >40% if platelet count was <10 x109/L. In contrast, a similar risk of severe bleeding was observed with all platelet count categories. Only slight differences were observed in other subgroups, except an increased frequency of any bleeding in case of exposure to NSAIDs, as well as an increased rate of severe bleeding in elderly and patients exposed to anticoagulant drugs and SRIs.In multivariate analysis, the factors associated with any bleeding at ITP diagnosis were a low platelet count (<10 x109/L vs. >20 x109/L: OR, 46.3, 95% CI: 19.4-110.6; between 10 and 19 x109/L vs. >20 x109/L: OR, 5.1, 95% CI: 2.3-11.2), female sex (OR for males, 0.4, 95%CI: 0.2-0.8) and exposure to NSAIDs (OR, 4.4, 95 %CI: 1.1-18.7). Only a low platelet count was associated with mucosal bleeding (<10 x109/L vs. >20 x109/L: OR, 6.2, 95% CI: 3.4-11.6; between 10 and 19 x109/L vs. >20 x109/L: OR, 2.6, 95% CI: 1.1-6.1). Lastly, only exposure to anticoagulant drugs was associated with severe bleeding (OR, 4.5, 95% CI: 1.4-14.4). Analyses restricted to primary ITPs led to similar results.Conclusion: Platelet counts <20 x109/L and <10 x109/L were thresholds with major increased risk for both any and mucosal bleedings. Platelet count, female sex and exposure to NSAIDs should be considered to assess the risk of any bleeding. In contrast, severe bleeding seemed not linked to platelet count but to individual factors, particularly exposure to anticoagulant. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Eltrombopag for myelodysplastic syndromes or chronic myelomonocytic leukaemia with no excess blasts and thrombocytopenia: a French multicentre retrospective real-life study.

Despite a moderate prevalence in low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), thrombocytopenia remains a risk of severe bleeding and therapeutic options are still limited. There are only a few studies with eltrombopag (ELT), a thrombopoietin receptor agonist, in those patients. In this retrospective multicentre study, ELT was used in 50 patients with MDS and 11 with CMML, with no excess of marrow blasts and platelet counts of <50×109 /l in a 'real-life' situation. Platelet response occurred in 47 (77%) patients. The median (range) duration of response was 8(0-69)months. None of the eight still responders who discontinued ELT had relapsed, at a median (range) of 16(6-23)months after ELT discontinuation. Although 36% of the patients were anti-coagulated or anti-aggregated only 10% of patients had Grade ≥3 bleeding events. Thrombotic events were observed in six (10%) patients, who all but one had a medical history of arterial or venous thrombosis. Progression to acute myeloid leukaemia occurred in four (7%) patients. In this first 'real-life' study, ELT was effective and generally well tolerated in patients with MDS/CMML without excess blasts.

New Developments in Diagnosis and Management of Acquired Hemophilia and Acquired von Willebrand Syndrome.

Acquired hemophilia A and acquired von Willebrand syndrome are rare, but life-threatening bleeding disorders that require prompt diagnosis and treatment by hematologists. Acquired hemophilia A is defined as an acquired severe bleeding tendency caused by autoantibody formation against coagulation factor VIII. Acquired von Willebrand syndrome is characterized by a new onset bleeding tendency caused by a reduced concentration and/or function of von Willebrand factor. These disorders are associated with a variety of underlying disorders, including various hematological malignancies, for example, plasma cell disorders, lymphoproliferative disorders, monoclonal gammopathy of undetermined significance, and myeloproliferative neoplasms. It is of utmost important to recognize these acquired bleeding disorders in these patients who are at risk for severe bleeding, and to perform additional diagnostic hemostasis laboratory evaluation. This will enable immediate diagnosis of the acquired bleeding disorder and management of both the bleeding episodes and the causative underlying disorder. In recent years, several new etiological factors for acquired hemophilia A, such as treatment with immune checkpoint inhibitors or DPP-4 inhibitors and SARS-CoV2 infection, and for acquired von Willebrand syndrome, for example, left ventricular assist devices, have been identified and also new treatment options have become available. In this concise review, the most recent data on etiology, diagnosis, and treatment of acquired bleeding disorders are presented and discussed.

FC 097INTERMITTENT HEMODIALYSIS WITHOUT ANTICOAGULATION

Abstract Background and Aims Dialysis therapy of patients at increased risk of bleeding is a well-known clinical problem. Systemic anticoagulation with heparin increases the risk of severe hemorrhage. Alternative strategies include the use of heparin-coated dialysis membranes, regional citrate anticoagulation, airless dialysis tubing, flushing the dialyzer with saline and earlier regional heparin anticoagulation with protamine reversal. However, either special devices (e.g. airless or heparin coated tubing) are needed, or the procedures are complex and require additional time and personnel resources for administration and monitoring. Current data on heparin-free dialysis are rare. After a pilot study from 282 dialysis sessions we reviewed 949 dialysis protocols from 2.5 years of 480 hospitalized and outpatient dialysis patients who were treated without systemic anticoagulation due to an increased risk of bleeding or a manifest hemorrhage. The duration of each dialysis session and the number of dialyses with or without clotting were evaluated. Method A total of 949 dialysis sessions of 480 patients were reviewed from October 2017 to January 2021. Dialysis were performed with Fresenius 4008/5008 (FX80,FX50, KF-210) and Gambro Artis (Poly170H, Theranova). All dialysis sessions were performed via AV-fistula with double-needle puncture or via single- or double-lumen central venous catheters (CVC). No additional technical devices or procedures were used beside standard hemodialysis or hemodiafiltration. Some of the patients had coagulopathies (sepsis, liver cirrhosis), thrombocytopenia or were on systemic anticoagulant therapy (vitamin K antagonists, DOAKs, heparin independent from dialysis therapy). The primary outcome was the need to interrupt the dialysis session because of clotting events due to a complete coagulation of the circuit, a partial coagulation of the circuit or a significant rise in the venous pressure. Results In 81 procedures (8.5%) systemic clotting made a discontinuation of the dialysis session necessary. In only 10 sessions (1%), the dialysis treatment had to be continued with new tubing and filter. More than one change of a system was never necessary. In the other 71 sessions, dialysis had to be stopped with retransfusion 5 minutes until 1.5 hours before the scheduled end of therapy, and therapy was considered as clinically sufficient. The frequency of clotting did not correlate with dialysis time (Fig.1.). Regarding the venous access clotting happened in 14.6% of acute CVC, in 12.6% of tunneled CVCs and in 9.4 % of AV-fistulas or -grafts, (Fig 2). Conclusion Dialysis without anticoagulation can be performed routinely with modern synthetic filters and dialysis concentrates. Patients at high risk of bleeding, with manifest hemorrhage or before surgery can undergo dialysis treatment for up to five hours without complications. In the present study clotting did not correlate with dialysis time. Patient-specific factors, as the venous access seem to play a more important role. In summary additional cost intensive devices, personnel intensive procedures and complex treatment protocols are only rarely needed to perform heparin-free dialysis for patients at risk.

HLA-DQB1 mismatch increase risk of severe bleeding independently in recipients of allogeneic stem cell transplant.

Severe bleeding is a major cause of death in acute leukemia (AL) patients with graft-versus-host disease (GVHD) after allogene hematopoietic stem-cell transplantation (allo-HSCT). However, the prognostic value and prediction of HSCT-associated severe bleeding in GVHD patients have not been reported in cohort studies. We did a retrospective analysis of 200 AL patients with GVHD after allo-HSCT from Feb 1, 2014, to Dec 1, 2015. Multivariate analysis showed that the severe bleeding class was associated with the risk of death (HR 2.26, 95% CI 1.31-3.92, p<0.001***). In order to predict severe bleeding and figure out the solution to bleeding events, we established a multiple logistic regression model. HLA-DQB1 unmatching, megakaryocyte reconsititution failure, and III or IV GVHD were the independent risk factors for severe bleeding. Among all the variations above, OR of HLA-DQB1 was the highest (OR: 16.02, 95% CI: 11.54-48.68). Adding HLA-DQB1 to other factors improved the reclassification for predicting severe bleeding (NRI=0.195, z=2.634, p=0.008**; IDI=0.289, z=3.249, p<0.001***). Lasso regression was used to select variants. A nomogram of the logistic model was generated and displayed. Calibration curve demonstrated excellent accuracy in estimating severe bleeding (C index of 0.935). HLA-DQB1 showed excellent efficacy of predicting severe bleeding in HSCT patients.

Narrative review of the contemporary surgical treatment of unicuspid aortic valve disease.

Unicuspid aortic valve disease (UAVD) is a frequent and long-lasting challenge for adult congenital heart disease centers. UAVD patients become usually symptomatic in their twenties or thirties and require a surgical treatment plan which should respect their complete lifespan combined with an adequate quality of life. Unfortunately, all current surgical strategies of congenital aortic valve disease bear some important limitations: (I) Aortic valve replacement using bioprosthetic valves is associated with early structural degeneration and leads frequently to re-operations. (II) Mechanical valves are commonly associated with lifelong risk of severe bleeding due to oral anticoagulation. (III) Using a pulmonary autograft (i.e., Ross procedure) for aortic valve replacement is associated with excellent long-term results in non-elderly patients. However, failure of pulmonary autograft or pulmonary homograft may require re-operations. (IV) Aortic valve repair or Ozaki procedure is only performed in a few heart centers worldwide and is associated with a limited reproducibility and early patch degeneration, suture dehiscence or increased risk of endocarditis. In contrast to degenerative tricuspid aortic valve disease, UAVD remains relatively understudied and reports on UAVD treatment are rare and usually limited to retrospective single-center observations. For this review, we searched PubMed for papers in the English language by using the search words unicuspid aortic valve, congenital aortic valve, Ross procedure, Ozaki procedure, aortic valve repair, mechanical/bioprosthetic aortic replacement, homograft. We read the abstracts of relevant titles to confirm their relevance, and the full papers were then extracted. References from extracted papers were checked for additional relevant reports. This review summarizes current surgical treatment strategies for UAVD including aortic valve replacement using bioprosthetic or mechanical valves, homografts, pulmonary autografts (i.e., Ross procedure) and aortic valve repair techniques for UAV. Furthermore, Ozaki procedure will be discussed.

Abstract MP4: Ticagrelor Plus Aspirin Versus Aspirin Alone in Acute Ischemic Stroke or TIA - Analysis of Bleeding Events in the THALES Trial

Introduction: In the THALES trial, ticagrelor and aspirin was superior to aspirin alone in reducing the primary endpoint of stroke or death, and subsequent disabling strokes, but increased risk of bleeding, as expected for dual antiplatelet therapy. Aim: Present the bleeding profile of ticagrelor in combination with aspirin in patients with acute cerebrovascular events. Methods: The THALES trial randomized patients with non-cardioembolic, non-severe ischemic stroke (NIHSS≤5) or high-risk TIA to ticagrelor (180mg loading dose on day 1 followed by 90mg twice daily until day 30) or placebo within 24h of symptom onset in 28 countries. All patients received aspirin 300-325mg on day 1 followed by 75-100mg daily until day 30. Primary safety endpoint was time to severe bleeding, defined by GUSTO criteria, within 30 days. Analyses were by intention to treat. (ClinicalTrials.gov number, NCT03354429). Results: Among 11016 patients randomized, 28 (0.5%) in the ticagrelor+aspirin group (T+A) and 7 (0.1%) in the aspirin group (A) had a severe bleeding event; HR 3.99 (1.74-9.14); p=0.001. Among these, 22 (0.4%) (T+A) vs 6 (0.1%) (A) were fatal or intracranial hemorrhages (ICHs) and 6 (0.1%) (T+A) vs 1 (&lt;0.1%) (A) non-fatal events with hemodynamic compromise. ICHs included 10 (0.2%) (T+A) vs 2 (&lt;0.1%) (A) hemorrhagic strokes and 4 (0.1%) (T+A) vs 2 (&lt;0.1%) (A) symptomatic haemorrhagic transformations of ischemic stroke and other ICHs. Most severe bleeding events were spontaneous; 1 (T+A) and 2 (A) were traumatic and 1 in each treatment group were procedural. No predefined subgroup was associated with severe bleeding risk though analyses were limited by a small number of events. Moderate/severe bleeding events occurred in 36 (0.7%) (T+A) vs 11 (0.2%) (A) patients. Bleeding leading to discontinuation occurred in 152 (2.8%) (T+A) vs 32 (0.6%) (A) patients. Conclusion: While the rate of severe bleeding in the patients with acute ischemic stroke or TIA was low, patients randomized to receive ticagrelor more often experienced severe bleeding events. No subgroup with different bleeding risk could be identified. Given the high risk of disability following a subsequent stroke, the benefit of adding ticagrelor to aspirin in reducing subsequent stroke appears to outweigh the risk of bleeding.

Abstract P25: Safety of Ticagrelor in Moderate to Severe Acute Ischemic Stroke: A Single-Center Retrospective Review

Introduction: Ticagrelor with aspirin has been recently shown to reduce the risk of stroke or death compared to aspirin alone in patients with high risk TIAs and mild strokes. However, this benefit is offset by increased risk of severe bleeding. We sought to evaluate the safety of ticagrelor in patients with moderate to severe ischemic stroke. Methods: This was a retrospective cohort study of adults discharged on ticagrelor after presenting with acute ischemic stroke and NIHSS &gt; 5 from January 2016 to December 2019 at a large, urban, academic comprehensive stroke center. Patients were excluded if they underwent carotid or intracranial angioplasty and/or stenting, or carotid endarterectomy during admission. Baseline clinical characteristics, imaging, and outcomes were reviewed. Data was organized into continuous and categorical variables. Results: Sixty-one patients met inclusion and exclusion criteria. Median age was 61 (IQR, 52-68) years; 33 (54%) were men, and 33 (54%) were African American. Median NIHSS was 11 (IQR, 8-15). Fourteen (23%) patients received IV Alteplase and 35 (57%) patients underwent mechanical thrombectomy. Five (8%) patients received both IV Alteplase and mechanical thrombectomy. Median ticagrelor start date was hospital day 1 (IQR, 0-3). Large artery atherosclerosis was presumed etiology in 53 (87%) patients. No patients experienced neurologic worsening, recurrent stroke, sICH, or major bleeding during inpatient stay. Sixty (98%) patients were on aspirin and ticagrelor at discharge. Follow-up information was available for 53 (87%) patients for a median duration of 3 (IQR, 2-6) months. Following discharge, 3 (5%) patients experienced recurrent ischemic stroke despite being compliant. One (2%) patient experienced major bleeding—gastrointestinal hemorrhage requiring transfusion—two months after hospital discharge. Conclusions: This study highlights the potential expanding role for ticagrelor in secondary stroke prevention in patients with moderate to severe stroke. Early ticagrelor use did not result in sICH during inpatient stay—and only 1 major bleeding event on follow-up—in our cohort. While further research in this area is needed, these findings present an exciting opportunity for future prospective studies.

Effect of Glomerular Filtration Rates on Outcomes Following Percutaneous Left Atrial Appendage Closure

Scarce data support the prescription of oral anticoagulation in patients with concomitant advanced chronic kidney disease (CKD) and atrial fibrillation, and left atrial appendage closure (LAAC) may provide a favorable risk-benefit ratio in this population. However, outcomes of LAAC in CKD patients are unknown. We aimed to investigate the impact of moderate-to-severe CKD on clinical outcomes following percutaneous LAAC. This was a multicenter study including 1094 patients who underwent LAAC. Moderate-to-severe CKD was defined as an eGFR<45 mL/min. Death, ischemic stroke, severe bleeding (≥BARC 3a) and serious adverse event (SAE; composite of death, stroke or severe bleeding) were recorded. A total of 300 patients (27.4%) had moderate-to-severe CKD. There were no differences between groups in periprocedural complications or device related thrombosis. At a median follow-up of 2 (1 to 3) years, patients with moderate-to-severe CKD did not present an increased risk of ischemic stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.22 to 1.92; p = 0.435) but were at a higher risk of death (HR: 2.84; 95% CI: 2.22 to 3.64; p <0.001), severe bleeding (HR: 1.96; 95% CI: 1.36 to 2.81; p <0.001) and SAE (HR: 2.23; 95% CI: 1.80 to 2.77; p <0.001). By multivariable analysis, an eGFR<45 ml/min (HR: 1.92; 95% CI: 1.34 to 2.76; p <0.001) and previous bleeding (HR: 2.30; 95% CI: 1.27 to 4.17; p = 0.006) were associated with an increased risk of severe bleeding. In conclusion, patients with moderate-to-severe CKD who underwent LAAC had very high thrombotic and bleeding risks. Although the rates of device related thrombosis or ischemic stroke after-LAAC were not influenced by kidney dysfunction, patients with moderate-to-severe CKD remained at higher risk of severe bleeding events.

Tratamento antitrombótico em pacientes portadores de fibrilação atrial e submetidos à revascularização coronária percutânea: terapia tripla versus dupla

The ideal antithrombotic management in patients with atrial fibrillation undergoing elective percutaneous coronary intervention or in acute coronary syndrome has not been definitively established yet. Dual antiplatelet therapy (aspirin and P2Y12 receptor inhibitors) reduces stent thrombosis and subsequent ischemic events. In turn, the presence of atrial fibrillation requires oral anticoagulation to prevent stroke and other thromboembolic complications. However, the combination of these two treatments, known as triple therapy, increases the risk of severe bleeding, with a negative prognostic impact. The use of direct anticoagulants, which reduce bleeding rates compared to warfarin, together with the maintenance of only one antiplatelet agent (P2Y12 inhibitors), known as dual therapy, may be a safer alternative in these patients. In this article, we reviewed several randomized studies comparing triple versus dual therapy, as well as meta-analyses with such studies, and the approaches suggested by the most recent guidelines, discussing the advantages and disadvantages of these treatments, in terms of safety and efficacy in this important and growing subgroup of patients.

Venous Thromboembolism and Major Bleeding in Patients With Coronavirus Disease 2019 (COVID-19): A Nationwide, Population-Based Cohort Study.

BackgroundVenous thromboembolism (VTE) is a potentially fatal complication of SARS-CoV-2 infection and thromboprophylaxis should be balanced against risk of bleeding. This study aimed to examine risks of VTE and major bleeding in hospitalized and community-managed SARS-CoV-2 patients compared with control populations.MethodsUsing nationwide population-based registries, 30-day risks of VTE and major bleeding in SARS-CoV-2 positive patients were compared with those of SARS-CoV-2 test-negative patients and with an external cohort of influenza patients. Medical records of all COVID-19 patients at six departments of infectious diseases in Denmark were reviewed in detail.ResultsThe overall 30-day risk of VTE was 0.4% (40/9,460) among SARS-CoV-2 patients (16% hospitalized), 0.3% (649/226,510) among SARS-CoV-2 negative subjects (12% hospitalized), and 1.0% (158/16,281) among influenza patients (59% hospitalized). VTE risks were higher and comparable in hospitalized SARS-CoV-2 positive (1.5%), SARS-CoV-2 negative (1.8%), and influenza patients (1.5%). Diagnosis of major bleeding was registered in 0.5% (47/9,460) of all SARS-CoV-2 positive individuals and in 2.3% of those hospitalized. Medical record review of 582 hospitalized SARS-CoV-2 patients observed VTE in 4% (19/450) and major bleeding in 0.4% (2/450) of ward patients, of whom 31% received thromboprophylaxis. Among intensive care patients (100% received thromboprophylaxis), risks were 7% (9/132) for VTE and 11% (15/132) for major bleeding.ConclusionsAmong people with SARS-CoV-2 infection in a population-based setting, VTE risks were low to moderate and were not substantially increased compared with SARS-CoV-2 test-negative and influenza patients. Risk of severe bleeding was low for ward patients, but mirrored VTE risk in the intensive care setting.

Risk of Severe Bleeding With Extended Rivaroxaban to Prevent Venous Thromboembolism in Acute Medically Ill Patients With Bronchiectasis.

Background: Bronchiectasis is a chronic inflammation of the bronchi with recurrent infections and hemoptysis. The MAGELLAN study compared oral rivaroxaban, 10 mg once daily (QD), for 35 ± 4 days with subcutaneous enoxaparin 40 mg QD for 10 ± 4 days followed by placebo for 25 ± 4 days to prevent venous thromboembolism in patients hospitalized with an acute medical illness. MAGELLAN included a subset of patients with bronchiectasis. In a post hoc analysis, we evaluated the incidence and severity of pulmonary bleeding in patients with bronchiectasis who were hospitalized for an acute medical illness. This analysis included MAGELLAN patients diagnosed with bronchiectasis at baseline. Patients were evaluated by treatment group for International Society on Thrombosis and Haemostasis major bleeding, non-major clinically relevant (NMCR) bleeding, and the composite of the 2 (ie, clinically relevant bleeding). Results: Medically ill patients with bronchiectasis were randomized to rivaroxaban (n = 60) or enoxaparin/placebo (n = 61). There were 2 fatal pulmonary bleeds and 1 fatal gastrointestinal bleed in the rivaroxaban arm and no fatal or major bleeding in the enoxaparin/placebo arm. The incidence of major bleeding was 5% in the rivaroxaban arm. One NMCR bleed occurred in the rivaroxaban arm and 2 NMCR bleeds occurred in the enoxaparin/placebo arm. The incidence of clinically relevant bleeding was 6.7% versus 3.3% in the rivaroxaban and enoxaparin/placebo groups, respectively (relative risk = 2.06 [95% confidence interval: 0.351-12.046]). Conclusion: In-patients hospitalized with bronchiectasis and an acute medical illness, clinically relevant bleeding, including fatal pulmonary hemorrhage, occurs more frequently with extended rivaroxaban thromboprophylaxis than with enoxaparin followed by placebo.

Intracranial hemorrhage detection

An intracranial hemorrhage is a kind of bleeding which occurs within the brain. The symptoms may vary based on the location of the hemorrhage, it may include total or limited loss of consciousness, abrupt shivering, numbness on one side of the body, loss of motion, serious migraine, drowsiness, problems with speech and swallowing. It is important to get the individual to a hospital and this condition must be treated as a medical emergency. Normally during this emergency, a Computerized Tomographic (CT) scan will be taken by the radiologist and they will identify the location of the hemorrhage and its subtypes. This process is often time consuming and complicated. Through this paper we would like to present a model which uses rich image dataset provided by Radiological Society of North America (RSNA) in collaboration with members of the American Society of Neuroradiology and MD.ai. This will help the medical community identify the presence, location and type of hemorrhage in order to quickly and effectively treat affected patients. This algorithm can provide early detection of people at high risk of severe bleeding in the brain. The algorithm comprises of a neural network architecture designed to detect intracranial hemorrhage while tackling several challenges such as relatively small bleed size and high variance within the brain, the algorithm executes this task by using InceptionV3 and DenseNet models.