Incidence Of Life-threatening Bleeding Research Articles

Abstract 10514: Inguinal Fat Tissue Biopsy to Identify Transthyretin Amyloidosis in Patients Undergoing Transcatheter Aortic Valve Implantation

Background: Several studies have recently reported that transthyretin (ATTR) amyloidosis is present in patients with aortic stenosis (AS). This study aimed to 1) examine the utility of inguinal fat tissue biopsy in AS patients who underwent transcatheter aortic valve implantation (TAVI) to detect ATTR amyloidosis, 2) compare clinical characteristics between AS patients with ATTR (ATTR group) and those without ATTR (non-ATTR group). Methods and Results: We prospectively analyzed consecutive 56 patients who underwent transfemoral TAVI from December 2018 to December 2020 in our hospital. To screen ATTR in these patients, we performed inguinal fat tissue biopsy from cut down or puncture site during TAVI. Of 56 AS patients, 5 (8.9%) patients were diagnosed as ATTR by inguinal fat biopsy. Compared with non-ATTR group, ATTR group presented higher levels of B-type natriuretic peptide (BNP, 566.4 vs. 242.5 ng/ml, P=0.0045), higher levels of troponin I (0.053 vs. 0.024 ng/ml, P=0.003), lower left ventricular ejection fraction (LVEF, 49.3 vs. 60.3%, P=0.0035), larger left ventricular mass index (150.2 vs. 115.5 g/m 2 , P=0.019), larger aortic valve area (0.84 vs. 0.63 cm 2 , P=0.029) and lower peak velocity of aortic valve (3.8 vs. 4.4 m/s, P=0.041). In contrast, age, sex, STS score, clinical frailty scale, prevalence of diabetes, chronic kidney disease and AF, levels of albumin, and eGFR were comparable between the two groups. Electrocardiogram and other echocardiographic parameters including interventricular septal wall thickness, posterior wall thickness, stroke volume index and E/A ratio did not differ between the two groups. Although TAVI was successfully completed in all patients, the incidence of life-threatening bleeding and 30-day readmission was higher in ATTR group than in non-ATTR group (40.0 vs. 5.9%, P=0.011 and 20.0 vs. 0.0%, P=0.001). There was no difference in occurrence of myocardial infarction, stroke, acute kidney injury, major vascular complication, pacemaker implantation and 30-day mortality. Conclusions: In AS patients, especially in those with increased BNP and troponin I levels and low-flow low-gradient pattern, ATTR should be considered. In this population, inguinal fat tissue biopsy is a novel and safe approach to identify ATTR.

Incidence and Clinical Outcomes of Thrombocytopenia after Transcatheter Aortic Valve Replacement in Thai Patients

Background: Post-transcatheter aortic valve replacement (TAVR) thrombocytopenia has been reported to be a predictor of higher mortality and worse clinical outcomes in published studies mostly from Western countries; however, data from Asian countries are generally limited, while data from Thai population are lacking. Objective: To evaluate the incidence and outcomes of Thai patients who developed thrombocytopenia after TAVR. Materials and Methods: The present research was a retrospective observational study. The authors collected data from patients underwent TAVR at Siriraj Hospital between 2009 and 2019. The patients were stratified into four groups according to nadir platelet count, no thrombocytopenia with platelet of 150,000/uL or more, mild with platelet of 100,000 to 149,999/uL, moderate at 50,000 to 99,999/uL and severe at less than 50,000/uL. In addition, the patients with moderate to severe thrombocytopenia were stratified into two groups according to the percentage decline in platelet count (DPC) post procedure as DPC of less than 50% or DPC of 50% or more from the baseline platelet count. Results: Eighty-three patients were reviewed. One patient who died intraoperatively was excluded. Thrombocytopenia occurred in 62 patients (75.6%), in which 36.6% (n=30) of the cases were classed as moderate, and 8.5% (n=7) as severe thrombocytopenia. The platelet count returned to baseline before discharge or during the follow-up period in 83.8% (n=52) of patients. The incidence of in-hospital mortality was significantly higher in patients with severe thrombocytopenia than those with mild thrombocytopenia at 28.6% versus 4% (p=0.011). The duration of admission, length of stay in the CCU, incidence of life-threatening bleeding, clopidogrel discontinuation, platelet transfusion, rate of infection, shock, and acute kidney injury were also significantly higher in patients with moderate to severe thrombocytopenia. Conclusion: Acquired thrombocytopenia after TAVR is a common phenomenon in Thai patients (75%) but usually transient with a nadir platelet count greater than 50,000/uL. Most patients had spontaneous platelet recovery. The presence of severe thrombocytopenia with a nadir platelet count of less than 50,000 is a red flag sign for concomitant infection. The severity of thrombocytopenia is significantly associated with higher mortality and post-procedural adverse events. Keywords: Thrombocytopenia; Transcatheter aortic valve replacement (TAVR)

Frailty and Bleeding in Older Adults Undergoing TAVR or SAVR: Insights From the FRAILTY-AVR Study

ObjectivesThe aim of this study was to examine the value of frailty to predict in-hospital major bleeding and determine its impact on mid-term mortality following transcatheter (TAVR) or surgical (SAVR) aortic valve replacement. BackgroundBleeding complications are harbingers of mortality and major morbidity in patients undergoing TAVR or SAVR. Despite the high prevalence of frailty in this population, little is known about its effects on bleeding risk. MethodsA post hoc analysis was performed of the multinational FRAILTY-AVR (Frailty Aortic Valve Replacement) cohort study, which prospectively enrolled older adults ≥70 years of age undergoing TAVR or SAVR. Trained researchers assessed frailty using a questionnaire and physical performance battery pre-procedure and ascertained clinical data from the electronic health record. The primary endpoint was major or life-threatening bleeding during the index hospitalization, and the secondary endpoint was units of packed red blood cells transfused. ResultsThe cohort consisted of 1,195 patients with a mean age of 81.3 ± 6.0 years. The incidence of life-threatening bleeding, major bleeding with a clinically apparent source, and major bleeding without a clinically apparent source was, respectively, 3%, 6%, and 9% in the TAVR group and 8%, 10%, and 31% in the SAVR group. Frailty measured using the Essential Frailty Toolset was an independent predictor of major bleeding and packed red blood cell transfusions in both groups. Major bleeding was associated with a 3-fold increase in 1-year mortality following TAVR (odds ratio: 3.40; 95% confidence interval: 2.22 to 5.21) and SAVR (odds ratio: 2.79; 95% confidence interval: 1.25 to 6.21). ConclusionsFrailty is associated with post-procedural major bleeding in older adults undergoing TAVR and SAVR, which is in turn associated with a higher risk for mid-term mortality.

Stroke Prevention in Atrial Fibrillation: A Clinical Perspective on Trials of the Novel Oral Anticoagulants.

Atrial fibrillation (AF) is a common heart rhythm disturbance; its incidence increases with age, and it is also an independent risk factor for stroke. Anticoagulation has been proven as the most effective way to reduce the risk of stroke in patients with AF, and vitamin K antagonists have been used for decades as the gold standard treatment. Vitamin K antagonists have a narrow therapeutic window in addition to variable pharmacokinetics and pharmacodynamics, and they frequently interact with food and other drugs, requiring coagulation monitoring to ensure balance between safety and efficacy. The novel oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban selectively target either thrombin or Factor Xa and have predictable pharmacologic profiles, removing the need for routine coagulation monitoring. This article summarizes phase III data in patient subtypes and discusses controversies surrounding AF management with these agents. Results indicate that NOACs in non-valvular AF have an overall improved efficacy–safety profile compared with warfarin. Significantly fewer fatal bleeding events were observed in patients randomized to rivaroxaban, apixaban, or edoxaban compared with those on warfarin, and significant reductions in the incidence of life-threatening bleeding were observed in patients randomized to dabigatran. All four pivotal trials testing the NOACs against warfarin showed significantly lower rates of intracranial bleeding in patients administered NOACs. These results suggest that wider use of NOACs has the potential to improve outcomes for most patients with AF.

Management of Dabigatran-associated Intracerebral and Intraventricular Hemorrhage: A Case Report

BackgroundDabigatran is an oral, reversibly bound, direct thrombin inhibitor currently approved in the United States for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In the phase III trial leading to approval of the agent, the incidence of life-threatening bleeding was 1.80%/year in the dabigatran 150 mg twice daily arm. Because there is no direct antidote or reversal agent for this drug, the need to manage life-threatening hemorrhages with procoagulant products will arise. ObjectiveTo describe a case of dabigatran-associated intracerebral and intraventricular hemorrhage and subsequent management with activated prothrombin complex concentrate. Case ReportAn 85-year-old man currently taking dabigatran 150 mg twice daily presented to the Emergency Department for incoordination, expressive aphasia, and weakness. A computed tomography image of his head demonstrated an intracranial hemorrhage. The last dose of dabigatran was approximately 14 h prior to arrival, and conventional coagulation assays (thrombin time and activated partial thromboplastin time) confirmed the presence of dabigatran in the patient's serum. The patient received 27.5 units/kg of activated prothrombin complex concentrate (FEIBA®; Baxter Healthcare Corporation, Deerfield, IL) after an initial intravenous fluid bolus. His activated partial thromboplastin time was not completely normalized by the use of FEIBA; however, the patient's neurological examination slightly improved and remained stable throughout his hospital course despite some intraventricular expansion of the hematoma. After discharge to physical rehabilitation, the patient developed an ischemic cerebrovascular accident and was discharged home on hospice. ConclusionDue to lack of an available antidote, activated prothrombin complex concentrate was utilized as a nonspecific procoagulant to stabilize an intracerebral hemorrhage in a patient on dabigatran.

Impact of Clopidogrel in Patients With Acute Coronary Syndromes Requiring Coronary Artery Bypass Surgery: A Multicenter Analysis

The purpose of our multicenter study was to examine the impact of pre-operative administration of clopidogrel on reoperation rates, incidence of life-threatening bleeding, inpatient length of stay, and other bleeding-related outcomes in acute coronary syndrome (ACS) patients requiring cardiopulmonary bypass (coronary artery bypass graft surgery [CABG]) in a broad cross section of U.S. hospitals. There is relative uncertainty about the relationship between clopidogrel and CABG-associated outcomes in the setting of ACS. A retrospective cohort analysis was performed of randomly selected ACS patients requiring CABG in 14 hospitals across the U.S. Patients exposed to clopidogrel were compared with those not exposed to clopidogrel within 5 days prior to surgery. Of the 596 patients enrolled in the study, 298 had been exposed to clopidogrel within 5 days (Group A). Patients in Group A were more than 3-fold more likely to require reoperation for assessment of bleeding than patients not exposed to clopidogrel (6.4% vs. 1.7% Group B, p = 0.004). Major bleeding occurred in 35% of Group A patients versus 26% of Group B patients (p = 0.049). Length of stay was greater in Group A compared with Group B (9.7 +/- 6.0 days vs. 8.6 +/- 4.7 days, unadjusted p = 0.016). After logistic regression analysis, clopidogrel exposure within 5 days of CABG was the strongest predictor of reoperation (odds ratio [OR]: 4.60, 95% confidence interval [CI]: 1.45 to 14.55) and major bleeding (OR: 1.824, 95% CI: 1.106 to 3.008). After ACS, patients who undergo CABG within 5 days of receiving clopidogrel are at increased risk for reoperation, major bleeding, and increased length of stay. These risks must be balanced by the clinical benefits of clopidogrel use demonstrated in randomized clinical trials.

Abstract 3221: Impact of Thienopyridines on Re-Operation Rates, Bleeding Outcomes and Hospitalization in ACS Patients Requiring CABG Surgery

Objective: The objective of this retrospective observational study is to examine the impact of preoperative administration of clopidogrel on re-operation rates, incidence of life-threatening bleeding, inpatient length of stay (LOS) and other bleeding-related outcomes in ACS patients requiring CABG in a broad cross-section of US hospitals. This is the first study designed with this objective to be conducted in multiple centers . Methods: A retrospective cohort analysis of ACS patients requiring CABG surgery during their index hospitalization was completed. Each site randomly selected 40–50 cases divided into the two comparison groups which consisted of patients exposed to clopidogrel versus those not exposed to clopidogrel within 5 days prior to surgery. Results: Data from the first 361 patients in 12 hospitals are reported. The two groups were comparable at baseline in terms of age, gender and co-morbidities. The rate of re-operation in the exposed group was 6.3% vs. 1.5% (p = 0.016) in those not exposed within 5 days. The number of patients who experienced excessive or life-threatening bleeding was higher in the exposed group; total inpatient LOS was not significantly different. Patients in the exposed group also required more blood product transfusions. Relationship between Clopidogrel Exposure and LOS, Markers for Life Threatening Bleeding, and Reoperation - Interim Analysis, 12 sites reporting Conclusion: Exposure to clopidogrel within 5 days before CABG surgery in ACS patients appears to significantly increase the need for re-operation and major bleeding outcomes in a broad cross-section of hospitals.

Management and Prognosis of Life-threatening Bleeding During Warfarin Therapy

The incidence of explicity defined life-threatening bleeding during warfarin sodium therapy is largely unknown, as are the prognosis for and treatment of patients who have such bleeding. In addition, the location of the source of the life-threatening bleeding and the risk factors associated with life-threatening bleeding are not well-defined.To determine the incidence of explicitly defined life-threatening bleeding during warfarin therapy, to identify the site of bleeding, to determine the risk factors for life-threatening bleeding, and to determine the risk of subsequent bleeding among patients receiving warfarin therapy.A cross-sectional prevalence study was conducted and data were combined with those obtained during prospective observation of a dynamic cohort of patients followed up in 2 university-affiliated and 3 Veterans Administration anticoagulation clinics.For this study, 1999 patients were followed up for 3865 patient-years; 32 patients (11 women, 21 men, mean age of 60 years) met criteria for life-threatening bleeding, an incidence of 0.83 events/100 patient-years (95% confidence interval, 0.54-1.12). The most common indication for warfarin was to prevent thromboembolism because the patient had a mechanical heart valve (17/32 patients, 53%). The gastrointestinal tract was the definite or likely site of bleeding in 21 (66%) of the 32 patients. The prothrombin time ratio was longer than 2.0 or the international normalized ratio was longer than 4.5 in 16 (55%) of the 29 patients in whom a coagulation time was measured. Fourteen (44%) of the 32 patients had a history of peptic ulcer disease or gastrointestinal bleeding. Warfarin was restarted in 26 (81%) of the 32 patients. Twenty-five of 26 patients were followed up for a median of 30 months (range, 5-143 months); 14 (56%) of the 25 patients had a subsequent bleeding event, with 8 (57%) of the 14 having 1 or more additional life-threatening bleeding events (1 fatal) after a median of 11.5 months (range, 0.5-22 months).We conclude that in this cohort: (1) the incidence of life-threatening bleeding was rare, (2) the gastrointestinal tract was the site of bleeding in two thirds of the patients who experienced life-threatening bleeding, (3) most patients who experienced life-threatening bleeding had multiple risk factors for bleeding, including excessive anticoagulation, and (4) the risk of subsequent bleeding was extremely high among the patients who continued to receive warfarin therapy.

Management and prognosis of life-threatening bleeding during warfarin therapy. National Consortium of Anticoagulation Clinics

The incidence of explicity defined life-threatening bleeding during warfarin sodium therapy is largely unknown, as are the prognosis for and treatment of patients who have such bleeding. In addition, the location of the source of the life-threatening bleeding and the risk factors associated with life-threatening bleeding are not well-defined. To determine the incidence of explicitly defined life-threatening bleeding during warfarin therapy, to identify the site of bleeding, to determine the risk factors for life-threatening bleeding, and to determine the risk of subsequent bleeding among patients receiving warfarin therapy. A cross-sectional prevalence study was conducted and data were combined with those obtained during prospective observation of a dynamic cohort of patients followed up in 2 university-affiliated and 3 Veterans Administration anticoagulation clinics. For this study, 1999 patients were followed up for 3865 patient-years; 32 patients (11 women, 21 men, mean age of 60 years) met criteria for life-threatening bleeding, an incidence of 0.83 events/100 patient-years (95% confidence interval, 0.54-1.12). The most common indication for warfarin was to prevent thromboembolism because the patient had a mechanical heart valve (17/32 patients, 53%). The gastrointestinal tract was the definite or likely site of bleeding in 21 (66%) of the 32 patients. The prothrombin time ratio was longer than 2.0 or the international normalized ratio was longer than 4.5 in 16 (55%) of the 29 patients in whom a coagulation time was measured. Fourteen (44%) of the 32 patients had a history of peptic ulcer disease or gastrointestinal bleeding. Warfarin was restarted in 26 (81%) of the 32 patients. Twenty-five of 26 patients were followed up for a median of 30 months (range, 5-143 months); 14 (56%) of the 25 patients had a subsequent bleeding event, with 8 (57%) of the 14 having 1 or more additional life-threatening bleeding events (1 fatal) after a median of 11.5 months (range, 0.5-22 months). We conclude that in this cohort: (1) the incidence of life-threatening bleeding was rare, (2) the gastrointestinal tract was the site of bleeding in two thirds of the patients who experienced life-threatening bleeding, (3) most patients who experienced life-threatening bleeding had multiple risk factors for bleeding, including excessive anticoagulation, and (4) the risk of subsequent bleeding was extremely high among the patients who continued to receive warfarin therapy.

Low incidence of life-threatening bleeding during warfarin therapy

Low incidence of life-threatening bleeding during warfarin therapy