Bleeding Rates In Patients Research Articles

Exploring bleeding in oral anticoagulant users: assessing incidence by indications and risk factors in the entire nationwide cohort.

Oral anticoagulants (OACs) are essential for the prevention and treatment of thromboembolic disorders, but bleeding, a major complication, can have a fatal impact on the patient's treatment. We aimed to estimate the nationwide, real-world incidence rate of bleeding in patients taking OACs and confirm the incidence by indications and risk factors. This cross-sectional study identified OAC users from April 1 to December 31, in both 2019 and 2020, using the HIRA-NPS database. The primary outcome variables were the incidence rate of major bleeding events during OAC treatment and within 30 days of treatment discontinuation. We estimated the adjusted incidence rate ratio (aIRR) in subpopulations. Among 18,822 OAC users, the incidence rate of major bleeding was 27.9 (95% CI: 24.6-31.5) per 1,000 person-years. The incidence rate of major bleeding was higher in patients with a bleeding history, with an aIRR of 11.51; those at high bleeding risk (HAS-BLED score ≥3), with an aIRR of 1.51; those with high CCI scores ≥3, with an aIRR of 1.88; and those with liver disease, with an aIRR of 1.41. For indications, compared to patients with nonvalvular atrial fibrillation (NVAF), the aIRR of major bleeding was significantly higher at an aIRR of 2.35 in patients undergoing VTE treatment. Patients with ischemic stroke showed a higher incidence of major bleeding with an aIRR of 2.13 than NVAF patients. The aIRR of major bleeding in the oral anticoagulant group, compared to the matched control group, was 2.25 (95% CI: 1.93-2.63). These findings may be useful for implementing strategies to improve the evaluation and management of anticoagulation-related bleeding.

Tenecteplase Versus Alteplase: A Comparison of Bleeding Outcomes in Massive Pulmonary Embolism (TACO-PE).

Thrombolysis is recommended in the setting of massive pulmonary embolism (PE) for reperfusion of vessels but carries a serious concern for increased bleed risk. In October 2022, our institution adopted tenecteplase as the formulary thrombolytic. Previous literature is unclear regarding the bleed risk of tenecteplase in massive PE, and no study has yet compared safety outcomes with the current standard of care, alteplase. The objective of this study was to compare the incidence of bleeding with tenecteplase versus alteplase in massive PE patients. This was a retrospective, observational cohort study that included adults who received tenecteplase or alteplase for massive PE. The primary outcome was major bleeding as defined by the International Society on Thrombosis and Hemostasis (ISTH). Secondary outcomes included incidence of symptomatic intracranial hemorrhage (ICH), in-hospital mortality, administration of reversal agents, and length of stay. A total of 44 patients met inclusion criteria with 20 patients in the alteplase cohort and 24 in the tenecteplase cohort. Seventeen percent of tenecteplase patients compared with 5% of alteplase patients experienced bleeding. The mortality rate was 83% vs 75%, respectively. In addition, 1 patient in the tenecteplase cohort experienced a symptomatic ICH and 2 patients required initiation of massive transfusion protocol. Although this study was limited in sample size, these results suggest that there may be reason for concern of higher bleeding rates in patients treated with tenecteplase in the setting of massive PE.

Use of the Canadian CT head rule for patients on anticoagulant/anti-platelet therapy presenting with mild traumatic brain injury: prospective observational study.

Background and importanceMild traumatic brain injury (mTBI) is a frequent presentation in Emergency Department (ED). There are standardised guidelines, the Canadian CT Head Rule (CCHR), for CT scan in mTBI that rule out patients on either anticoagulant or anti-platelet therapy. All patients with these therapies undergo a CT scan irrespectively of other consideration.ObjectiveTo determine whether standard guidelines could be applied to patients on anticoagulants or anti-platelet drugs.Design, settings, and participants1,015 patients with mTBI and Glasgow Coma Score (GCS) of 15 were prospectively recruited, 509 either on anticoagulant or anti-platelet therapy and 506 on neither. All patients on neither therapy underwent CT scan following guidelines. All patients with mTBI on either therapy underwent CT scan irrespective of the guidelines.Outcome measure and analysisPrimary endpoint was the incidence of post-traumatic intracranial bleeding in patients either on anticoagulants or anti-platelet drugs and in patients who were not on these therapies. Bayesian statistical analysis with calculation of Confidence Intervals (CI) was then performed.Main resultsSixty scans were positive for bleeding: 59 patients fulfilled the criteria and 1 did not. Amongst patients with haemorrhage, 24 were on either therapy and only one did not meet the guidelines but in this patient the CT scan was performed before 2 h from the mTBI. Patients on either therapy did not have higher bleeding rates than patients on neither. There were higher bleeding rates in patients on anti-platelet therapy who met the guidelines vs. patients who did not. These rates overlapped with patients on neither therapy, meeting CCHR.ConclusionThe CCHR might be used for mTBI patients on either therapy. Anticoagulants and anti-platelet drugs should not be considered a risk factor for patients with mTBI and a GCS of 15. Multicentric studies are needed to confirm this result.

Antithrombotic drug removal with hemoadsorption during off-pump coronary artery bypass grafting

BackgroundPatients requiring coronary artery bypass grafting (CABG) are often loaded with antithrombotic drugs (AT) and are at an increased risk for perioperative bleeding complications. Active AT removal by a hemoadsorption cartridge integrated in the cardiopulmonary bypass circuit is increasingly used in this setting to reduce bleeding, and herein we describe the extension of this application in patients on AT undergoing off-pump coronary artery bypass (OPCAB).MethodsTen patients (80% male; mean age: 67.4 ± 9.2years) were treated with ticagrelor (eight patients), rivaroxaban and ticagrelor (one patient), and rivaroxaban (one patient) prior to OPCAB surgery. AT’s were discontinued one day before surgery in nine patients and on the day of surgery in one patient, and all patients were also on aspirin. The cohort mean EuroSCORE-II was 2.9 ± 1.5%. A hemoadsorption cartridge was integrated into a dialysis device (n=4) or a stand-alone apheresis pump (n=6) periprocedural, for a treatment time of 145 ± 33 min. Outcome measures included bleeding according to Bleeding Academic Research Consortium (BARC)-4 and 24-hour chest-tube-drainage (CTD).ResultsMean operation time was 184 ± 35 min. All patients received a left internal thoracic artery with a mean of 2.3 ± 0.9 total grafts. One patient had a BARC-4 bleeding event and there were no surgical re-explorations for bleeding. Mean 24-hours CTD was 680 ± 307mL. During follow-up of 19.5 ± 17.0 months, none of the patients died or required further reinterventions. No device-related adverse events were reported.ConclusionsHemoadsorption via a stand-alone apheresis pump during OPCAB surgery was feasible and safe. This innovative and new approach showed favorable bleeding rates in patients on antithrombotic drugs requiring bypass surgery.

Long-term survival in venous thromboembolic disease: rivaroxaban vs. warfarin – propensity score matching study

BackgroundVenous thromboembolic disease (VTE) is characterized by obstruction of venous blood flow by a thrombus. Survival data, frequency of disease recurrence, and bleeding rate in patients on anticoagulant therapy with warfarin compared to rivaroxaban in the Latin American population are limited in VTE.MethodsA retrospective cohort study with propensity score matching analysis was conducted in patients with pulmonary embolism and/or deep vein thrombosis anticoagulated with warfarin or rivaroxaban treated. Survival analysis was performed using a Kaplan-Meier curve for each of the intervention groups, and it was compared using a Log Rank test.ResultsOf 2193 potentially eligible patients with a suspected diagnosis of VTE, 505 patients entered the analysis; of these, 285 subjects were managed with warfarin and 220 anticoagulated with rivaroxaban. Major bleeding at 12 months occurred in 2.7% (6/220) of patients treated with Rivaroxaban, compared to 10.2% (29/285) in the Warfarin group in the unmatched population (p = 0.001). In the matched population, bleeding at 12 months occurred in 2.9% (6/209) of patients on Rivaroxaban and in 11.0% (23/209) of patients on Warfarin (p = 0.001). The survival rates at 6 months were 97.1% for Rivaroxaban and 97.6% for Warfarin (p = 0.76). At 12 months, the survival rates were 94.7% for Rivaroxaban and 95.7% for Warfarin (p = 0.61).ConclusionIn the treatment of VTE, there is no differences on 6 and 12-month survival or a reduction in the occurrence of new thromboembolic events when comparing rivaroxaban to warfarin. However, a lower risk of major bleeding is observed at 12 months with Rivaroxaban.

Bleeding Risk from Anticoagulant Thromboprophylaxis in Patients with Multiple Myeloma

Introduction: Patients with multiple myeloma (MM) have a high risk of venous thromboembolism (VTE) due to unique disease-related (i.e., vascular inflammation, hyperviscosity) and treatment-related factors (i.e., immunomodulatory drugs [IMiDs], high-dose dexamethasone). Thromboprophylaxis is recommended for most patients starting MM therapy. Anticoagulants are preferred over aspirin except in patients at low risk for VTE. However, compliance with prophylaxis guidelines is low. The risk of bleeding from thromboprophylaxis is not well described in these patients so an excessive perceived risk may influence clinicians' practice. We conducted a real-world analysis of bleeding complications from VTE prophylaxis in MM. Methods: The IBM MarketScan Commercial Claims Database was used to identify MM cases between 2013 and 2021. Cases required MM diagnosis from 1 inpatient or 2 outpatient claims, based on ICD-9 or ICD-10 codes, and MM-specific therapy started between 7 days before and 90 days after index diagnosis code, based on HCPCS codes and prescription records. Those with preexisting VTE, atrial fibrillation or stroke were excluded. Thromboprophylaxis was defined as at least 1 prescription for warfarin, low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOAC) within 30 days of diagnosis. Major bleeding was defined as bleeding requiring hospitalization using inpatient ICD codes previously validated (Cunningham algorithm). Patients were followed from end of prophylaxis exposure window (index MM + 30 days) to first major bleeding event, disenrollment (due to death or other reasons) or December 31, 2021. Descriptive statistics were used to calculate rates of bleeding. Cox regression was used to assess the risk of bleeding from thromboprophylaxis and define risk factors associated with major bleeding. Results: We included 6,656 patients diagnosed and treated for MM, with mean age 62.7 years and 55.3% males. Although over 50% of the population would have had a high thrombotic risk based on consensus guidelines, concurrent anticoagulant prophylaxis was prescribed in only 6.6% (436). Prophylaxis agent of choice was warfarin in 23% (102), LMWH in 39% (169), and DOAC in 38% (165), respectively. There was a trend over time favoring DOAC over other agents (25% increase in DOAC use vs. other agents per year on average, p<0.01). Patients on prophylaxis had a higher rate of IMiD-based therapy (63.8% vs. 46.7%, p<0.01) and lower concomitant anti-platelet use (2.1% vs. 4.7%, p=0.01) than those not receiving prophylaxis. There were no differences in age/sex distribution, Charlson comorbidity index (CCI) or history of bleeding between groups. With a median 1.3 years follow-up, the incidence of major bleeding among MM patients receiving VTE prophylaxis was 1.4% or 7.8 bleeding events per 1,000 person-years. This was numerically but not statistically lower than the incident bleeding rate in patients not receiving prophylaxis: 1.8% or 10.1 events per 1,000 person-years. Table 1 shows risk factors for bleeding in this MM population, adjusting for age and sex, including higher age (per 10-year increase, HR 1.38), higher CCI (per SD increment, HR 1.18), history of bleeding (HR 1.54), hypertension (HR 1.87), and renal disease (HR 1.56). IMiD-based MM therapy was associated with decreased risk of bleeding (HR 0.69). Table 2 shows the estimated bleeding risk associated with prophylaxis across several models. No statistically significant association was identified between major bleeding and anticoagulant prophylaxis. Discussion: In a real-world analysis of commercial claims data, the risk of major bleeding associated with VTE prophylaxis in patients with MM undergoing cancer therapy is low and no significant increase in bleeding risk was identified for concurrent anticoagulant use. The rate of major bleeding events appears to be comparable between patients who receive VTE prophylaxis and those who do not. Nevertheless, underutilization of VTE prophylaxis is frequent. Higher CCI, bleeding history, hypertension, and renal disease were clinical factors associated bleeding risk, which may be included in models to help clinicians assess individual patient's risk and guide clinical decisions.

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year follow-up of more than 13,000 patients from the ETNA-AF-Europe study

Abstract Background Direct, non-vitamin K antagonist oral anticoagulants (DOACs/NOACs) have become the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF) at risk of stroke. Data on long-term effectiveness and safety of NOACs are scarce and not available from randomised clinical trials. Purpose We analysed 4-year outcome data in 13,632 European patients with AF treated with the NOAC, edoxaban. Methods This is the first report of the four-year follow-up information collected in the ETNA-AF-Europe (NCT02944019) study. It is a prospective registry, conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Design and follow-up were agreed with the European Medicines Agency as part of the post-approval safety assessment of edoxaban. Key efficacy and safety outcomes were adjudicated. Results 13,164 patients (56.7% males) with AF treated with edoxaban (60 mg OD n=9617; 30 mg OD n=3042; missing dose n=505) were analysed: median (interquartile range [IQR]) age was 75 (68–80) years, weight 80 (70–90) kg, creatinine clearance (CrCl) 68.9 (52.7–87.9) mL/min, modified CHA2DS2-VASc and HAS-BLED scores 3 (2–4) and 2 (1–2), respectively in the overall population. Annualised all-cause and cardiovascular deaths in the overall population were 4.1%/year and 1.0%/year, respectively; higher in the edoxaban 30 mg vs 60 mg cohort (Figure 1). Annualised rates of stroke, transient ischaemic attack and systemic embolic events rates were <1% (0.6%/year, 0.3%/year and 0.1%/year, respectively); these proportions were similar between the two dose cohorts (Figure 1). The time-to-first event curves for all-cause death, stroke and major bleeding were almost linear throughout the 4-year follow-up (Figure 2), irrespective of dose cohort. Compared with patients receiving edoxaban 60 mg, those prescribed 30 mg were older (median [IQR] age: 80 [75–85] vs 73 [66–78] years), had greater frail proportion (27.0% vs 6.6%), a lower CrCl (46.1 [37.4–59.0] vs 75.9 [61.9–93.8] mL/min) and a higher CHA2DS2-VASc score (4 [3–5] vs 3 [2–4]). Annualised bleeding rate was 3.0%/year and higher in the 30 mg vs 60 mg cohort (Figure 1). Annualised major bleeding, intracranial haemorrhage (ICH) and major gastrointestinal (GI) bleeding rates were low (0.9%/year, 0.2%/year and 0.4%/year, respectively), with higher major bleeding and major GI bleeding rates in patients treated with edoxaban 30 mg OD (Figure 1). ICH rates were similar in both dose cohorts. Conclusion These findings illustrate the long-term effectiveness and safety of edoxaban. Treatment with edoxaban over 4 years in patients with AF is associated with a relatively low, linearly increasing rate of all-cause death and ischaemic stroke. Rates of bleeding and especially ICH rates were low.

Safety and efficacy of protamine administration for prevention of bleeding complications in patients with recent PCI undergoing TAVR

Abstract Background Despite major advances, TAVR is still associated with vascular and bleeding complications, that have an impact on mortality. Recent studies have shown that heparin antagonization using protamine resulted in lower bleeding rates in patients undergoing TAVR as compared to those without heparin reversal. However, there are only limited data on the safety of protamine regarding thromboembolic complications including in-stent thrombosis in TAVR patients who have had a recent PCI. Accordingly, daily practice varies between Centers. Purpose The aim of this multicentre study was to evaluate the safety and efficacy of protamine administration in patients who have had a recent PCI undergoing subsequent TAVR. Methods Our study included 1838 patients undergoing TAVI between 2017 and 2020. Of the patients included, 173 (9.4%) had a recent PCI (≤30 days), 319 (17.4%) had an intermediately (≥30 days) and 303 (16.5%) a previously performed PCI (≥6 months). Standardized vascular access management included the use of preclosure devices and PTA or implantation of a stent-graft, if necessary. The primary endpoint was a composite of one-year mortality and myocardial infarction at 30 days. Secondary endpoints included 30-day mortality and VARC-3-defined complications. Results The overall study population had a mean age of 81.1±6.2 years. Among patients with recent PCI, 134 (77.5%) patients received protamine for heparin reversal during the TAVR procedure. In the group of patients with intermediately and previously performed PCI 258 (80.9%) and 249 (82.2%) patients received protamine, respectively. In the recent PCI group, the occurrence of the primary endpoint was comparable between patients with protamine administration (24.6%) as compared to patients without heparin reversal (30.8%, p=0.53, Figure 1). Similarly, among patients with intermediately as well as previously performed PCI, the rates of the primary endpoint were comparable irrespective of protamine administration (20.1 vs 16.4%, p=0.59; 17.3 vs 27.7%, p=0.08, respectively, Figure 2). Moreover, among all three groups, the incidence of myocardial infarction at 30 days after TAVR was low and comparable between patients with and without heparin reversal (p>0.50). Overall, protamine administration was associated with decreased life-threatening bleeding (3.2 vs 9.4%, p<0.01) and major vascular complications (4.4 vs 7.9%, p=.02). Regarding safety endpoints, no overall differences were observed in the incidence of stroke between patients with and without protamine administration (1.5 vs 2.9%, p=0.13). Conclusion Protamine administration during the TAVR procedure did not increase the rate of myocardial infarction or one-year mortality in patients who have had a recently or intermediately performed PCI. Overall, heparin reversal using protamine resulted in significantly lower rates of life-threatening bleeding and major vascular complications, without increasing the incidence of stroke.Figure 1Figure 2

Risk of Bleeding After Percutaneous Endoscopic Gastrostomy in Patients Using Antithrombotic Drugs.

The rate of using antithrombotic (AT) drugs is frequently high in patients who require percutaneous endoscopic gastrostomy (PEG). The aim of this study was to determine whether the risk of bleeding after PEG increases in patients whose AT drugs were discontinued according to the European Society Gastrointestinal Endoscopy guidelines (warfarin for 5d, low molecular weight heparin for 24h, DOAC for 3d, and clopidogrel for 7d). Data from 243 patients, who underwent PEG tube placement and received AT drugs and 206 patients who did not between 2018 and 2021 in our hospital, were evaluated retrospectively. Bleeding was defined as requiring blood transfusion, hematemesis and/or melena, decreased hemoglobin, or bleeding from PEG. A total of 243 (54.1%) patients (121 (49.7%), women, mean age (75.7y) who underwent PEG and received AT drugs, and 206 (45.9%) patients who did not (92 (44.6%), women, mean age (63.15y). The medications and bleeding rates of the patients are given in Table 1. The rate of bleeding in patients using AT medication was significantly higher than that in patients not using medication (Table 2) ( P = 0.007). When the AT drugs were compared among themselves, the bleeding risk did not differ. Bleeding was detected in 10 patients with bleeding from the PEG tube in 4 with melena. Bleeding detected in 14 patients was controlled with adrenaline injections. None of the patients required transfusion or repeat endoscopies. No bleeding-related deaths were reported. Even if patients receiving AT drugs are treated as recommended by international guidelines, it should be kept in mind that bleeding may occur after PEG, and the patients should be followed accordingly.

Influence of thrombocytopenia on bleeding and vascular events in atrial fibrillation

AbstractWhether thrombocytopenia substantively increases the risk of hemorrhage associated with anticoagulation in patients with atrial fibrillation (AF) is not established. The purpose of this study was to compare rates of bleeding in patients with AF and thrombocytopenia (platelet count < 100 000/μL) to patients with AF and normal platelet counts (>150 000/μL). We performed a propensity score–matched, retrospective cohort study of adults (n = 1070) with a new diagnosis of AF who received a prescription for an oral anticoagulant between 2015 and 2020. The thrombocytopenia cohort was defined as having at least 2 platelet counts <100 000/μL on separate days in the period spanning the 12 weeks preceding the initiation of anticoagulation to 6 weeks after the initiation of anticoagulation. The primary end point was the 1-year cumulative incidence of major bleeding; secondary end points included clinically relevant bleeding, arterial and venous thrombotic events, and all-cause mortality. Patients with AF and thrombocytopenia experienced a higher 1-year cumulative incidence of major bleeding (13.3% vs 5.7%; P < .0001) and clinically relevant bleeding (24.5% vs 16.7%; P = .005) than the controls. Thrombocytopenia was identified as an independent risk factor for major bleeding (hazard ratio, 2.20; confidence interval, 1.36-3.58; P = .001), with increasing risk based on the severity of thrombocytopenia. The cumulative incidence of arterial thrombosis at 1 year was 3.6% in the group with thrombocytopenia and 1.5% in controls (Gray test, P = .08). These findings suggest that baseline platelet counts are an important biomarker for hemorrhagic outcomes in AF and that the degree of thrombocytopenia is an important factor in determining the level of risk.

Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial.

Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC). The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH). The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups. During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.

Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer

In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain. To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event. Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020. Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses. The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin. Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death. Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer. ClinicalTrials.gov Identifier: NCT02744092.

Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants.

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection (ESD) for early-stage gastrointestinal tumors. The rate of post-ESD bleeding for gastric cancer is higher (around 5%-8%) than that for esophagus, duodenum and colon cancer (around 2%-4%). Although investigations into the risk factors for post-ESD bleeding have identified several procedure-, lesion-, physician- and patient-related factors, use of antithrombotic drugs, especially anticoagulants [direct oral anticoagulants (DOACs) and warfarin], is thought to be the biggest risk factor for post-ESD bleeding. In fact, the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%, which is higher than that in patients not receiving anticoagulants. However, because clinical guidelines for management of ESD in patients receiving DOACs differ among countries, it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice. Given that the pharmacokinetics (e.g., plasma DOAC level at both trough and Tmax) and pharmacodynamics (e.g., anti-factor Xa activity) of DOACs are related to risk of major bleeding, plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

Comparison of Safety and Effectiveness of Local or General Anesthesia after Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis.

It remains controversial to choose anesthesia for transcatheter aortic valve implantation (TAVI). A meta-analysis of cohort studies was conducted to assess the efficacy and safety of local anesthesia (LA) compared to general anesthesia (GA) in TAVI. All relevant studies published from 1 January 2002, to 31 June 2022, were searched in Ovid, PubMed, Embase, Web of Science, and Cochrane Library. A total of 34 studies involving 23,480 patients were included in the meta-analysis. TAVI with LA was associated with a significant reduction in hospital stay [WMD = −2.48, 95% CI (−2.80, −2.16), p < 0.00001], operative [WMD = −12.25, 95% CI (−13.73, −10.78), p < 0.00001] and fluoroscopy time [WMD = −3.30, 95% CI (−5.40, −1.19), p = 0.002], and an increased risk of acute kidney injury [OR = 1.31, 95% CI (1.01, 1.69), p = 0.04] and a reduced incidence of major bleeding [OR = 0.59, 95% CI (0.46, 0.75), p < 0.0001] and the use of cardiovascular drugs [OR = 0.17, 95% CI (0.05, 0.57), p = 0.004]. No differences were found between LA and GA for 30-day mortality, procedural success rate, myocardial infarction, permanent pacemaker implantation, paravalvular leak, shock, and cerebrovascular events. Overall, 4.4% of LA converted to GA. Based on current evidence, our results suggested that LA strategies reduced hospital stay, operative time, fluoroscopy time, cardiovascular drug consumption, and major bleeding rates in patients undergoing TAVI but led to increased acute kidney injury rates. Further studies and randomized trials are required to verify the presented findings and to identify patients who might benefit from LA.

Bleeding in neonates with severe thrombocytopenia: a retrospective cohort study

BackgroundSevere neonatal thrombocytopenia is a rare disease with multiple etiologies. Severe thrombocytopenia with bleeding is life-threatening and has attracted significant attention from clinicians. However, only a few studies have focused on the association between severe thrombocytopenia and bleeding. Thus, this study aimed to describe the neonates’ postnatal age at which severe thrombocytopenia was first recognized, clinical characteristics, bleeding patterns, and outcomes and to evaluate the association between minimum platelet count and bleeding.MethodsA single-center retrospective cohort study for neonates with severe thrombocytopenia (platelet count ≤ 50 × 109/L) was conducted. Neonates who were admitted to our neonatal intensive care unit between October 2016 and February 2021 and developed severe thrombocytopenia were analyzed. Data were collected retrospectively until the patients were referred to other hospitals, discharged, or deceased.ResultsAmong the 5819 neonatal inpatients, 170 with severe thrombocytopenia were included in this study. More than 30% of the patients had severe thrombocytopenia in the first 3 days of life. Among the 118 neonates with bleeding, 47 had more than one type of pathological bleeding. Neonates with very severe thrombocytopenia (point estimate: 53.7%, 95% confidence interval [CI]: 44.2%–63.1%) had a higher incidence rate of cutaneous bleeding than those with severe thrombocytopenia (point estimate: 23.4%, 95% CI: 12.3%–34.4%). The gestational age (median: 36.2 [interquartile range [IQR]: 31.4–39.0] weeks) and birth weight (median: 2310 [IQR: 1213–3210] g) of the major bleeding group were the lowest among no bleeding, minor bleeding, and major bleeding groups. Regression analysis controlled for confounders and confirmed that a lower platelet count (odds ratio [OR]: 2.504 [95% CI: 1.180–5.314], P = 0.017) was associated with a significant increase in the rate of bleeding. Very severe thrombocytopenia (point estimate: 49.1%, 95% CI: 39.6%–58.6%) had a higher rate of platelet transfusion than severe thrombocytopenia (point estimate: 5.7%, 95% CI: 0.7%–10.7%). The mortality rate was higher in neonates with bleeding than in those without bleeding (point estimates with 95% CI: 33.1% [24.4%–41.7%] vs. 7.7% [0.2%–15.2%]).ConclusionsThese findings describe the incidence of severe thrombocytopenia and demonstrate that a lower platelet count is associated with an increased bleeding rate in patients with severe thrombocytopenia.

The Safety of Direct Oral Anticoagulants Compared to Warfarin in Patients Hospitalized With Acute Kidney Injury.

Direct oral anticoagulants (DOACs) are preferred over warfarin for many indications, though their safety has not been well established in patients with acute renal impairment. The purpose of this study was to evaluate the frequency of bleeding complications associated with DOACs compared with warfarin in patients admitted to the hospital with acute kidney injury (AKI). This was a retrospective cohort study evaluating patients admitted to the Penn Medicine Lancaster General Hospital with a diagnosis of AKI from October 2017 through September 2021 and receiving therapy with oral anticoagulants. Comparing DOACs with warfarin, the primary endpoint was the percent frequency of composite major and minor bleeding during the admission and within 30 days of discharge. There were 112 hospitalization encounters included in the study. Of these, 42 (37.5%) patients were receiving warfarin and 70 (62.5%) patients were receiving DOAC therapy before admission. There was a higher frequency of the primary endpoint of bleeding in patients receiving DOACs as compared with warfarin, though this was not statistically significant (18.5% vs. 11.9%, respectively, P = 0.432). There were no differences between groups in the frequency of major bleeding, minor bleeding, or transfusions. Patients receiving DOAC therapy were more likely to experience anticoagulation-related readmissions or emergency department visits compared with patients on warfarin therapy (11.4% vs. 0%, P = 0.024). Direct oral anticoagulants and warfarin were associated with statistically similar rates of bleeding in patients presenting with AKI. Further research is necessary to elucidate if DOACs are safer than warfarin in this patient population.

Optimal Timing of Perioperative Chemical Thromboprophylaxis in Elective Major Abdominal Surgery: A Systematic Review and Meta-analysis.

To investigate the effect of the timing of chemoprophylaxis on venous thromboembolisms (VTEs) and bleeding rates in patients undergoing major abdominal surgery. Postoperative bleeding and VTE incur significant morbidity, mortality, and health care costs. Chemoprophylaxis is used routinely to prevent VTEs but increases bleeding risk. The perioperative timing of chemoprophylaxis initiation may influence both VTE and bleeding risks. The optimal window for commencing chemoprophylaxis in the perioperative period is unclear. MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched using PRISMA guidelines. Randomized trials and cohort studies published between January 1, 2000 to May 10, 2022, which reported on chemoprophylaxis timing as well as the incidence of VTE and bleeding after elective abdominal surgery were meta-analyzed. From 6175 studies, 14 (24,922 patients) were meta-analyzed. Bariatric (4 studies), antireflux (1 study), hepato-pancreatic-biliary (5 studies), colorectal (1 study), ventral hernia (1 study), and major intra-abdominal surgeries (2 studies) were included. Chemoprophylaxis was initiated before skin closure in 10,403 patients, and postoperatively in 14,519 patients. Both symptomatic [risk ratios (RR), 0.81; 95% CI, 0.45-1.43; P =0.460] and overall (RR, 0.74; 95% CI, 0.45-1.24; P =0.250) VTE rates were comparable between study groups. Compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (RR, 1.56; 95% CI, 1.13-2.15; P =0.007), major bleeding (RR, 1.63; 95% CI, 1.16-2.28; P =0.005), blood transfusion (RR, 1.48; 95% CI, 1.24-1.76; P <0.001), and reintervention (RR, 1.94; 95% CI, 1.19-3.18; P =0.008). Our findings advocate for initiating chemoprophylaxis postoperatively in elective abdominal surgery to minimize bleeding risk without compromising VTE protection.

Evaluation of standard versus reduced dose apixaban for the treatment of venous thromboembolism in patients with severe renal disease (ESRD-VTE)

BackgroundThere are no clear dosing recommendations when using apixaban for venous thromboembolism (VTE) treatment in patients with severe or end-stage renal disease; clinical trials excluded patients with a creatinine clearance (CrCl) <25 mL/min or on dialysis. This study compares bleeding rates in patients with severe or end-stage renal disease taking standard versus reduced dose apixaban for VTE treatment. Materials and methodsThis was a multicenter, retrospective cohort study using electronic medical records between January 1, 2013, and August 31, 2021. This study included patients 18 years or older who had severe or end-stage renal disease when prescribed apixaban for VTE treatment. Severe or end-stage renal disease was defined as at least one of the following: CrCl <25 mL/min, SCr >2.5 mg/dL, CKD stage 4 or 5, or on dialysis. The primary endpoint was rate of clinically relevant bleeding within six months of starting apixaban. Secondary endpoints were VTE recurrence within six months of starting apixaban, time to clinically relevant bleed, and time to VTE recurrence. ResultsA total of 203 patients were included in the final analysis (n = 125 on 5 mg; n = 78 on 2.5 mg). Clinically relevant bleeding rate was significantly higher in the standard dose group (14.4 % vs 3.8 %, p = 0.02). Rates of VTE recurrence appear similar (6.4 % vs 7.7 %, p = 0.21). ConclusionsA reduced dose of apixaban may be considered when treating VTE in patients with severe or end-stage renal disease.

Propofol versus midazolam sedation in patients with cardiogenic shock – an observational propensity-matched study

Abstract Introduction Benzodiazepines are recommended as first line sedative agent in ventilated cardiogenic shock patients, although data regarding the optimal sedation strategy are sparse. On our cardiac ICU, midazolam was used as first line sedation until 2016, whereas soybean oil formulated propofol was used preferentially since 2017. Purpose The aim of this study was to investigate the hemodynamic effects of propofol versus midazolam sedation in our cardiogenic shock registry. Methods Mechanically ventilated patients suffering from cardiogenic shock were retrospectively enrolled from a cardiogenic shock registry. 174 patients treated predominantly with propofol were matched by propensity-score to 174 patients treated predominantly with midazolam. Results Catecholamine doses were similar on admission but significantly lower in the propofol group on days 1–4 of ICU stay (Figure 1). Mortality rate was 38% in the propofol and 52% in the midazolam group after 30 days (p=0.002, Figure 2). Rate of ≥BARC3 bleeding was significantly lower in the propofol group compared to the midazolam group (p=0.008). Age, gender, first lactate measured on ICU, first GFR measured on ICU, cardiac arrest, coaxial left ventricular assist device and sedation with midazolam were significantly associated with ICU mortality. Conclusion In this observational cohort study, sedation with propofol in comparison to midazolam was linked to a reduced dose of catecholamines, decreased mortality and bleeding rates for patients with cardiogenic shock. Based on this study and in contrast to current recommendations, propofol should be given consideration for sedation in cardiogenic shock patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

Propofol versus midazolam sedation in patients with cardiogenic shock - an observational propensity-matched study.

Benzodiazepines are recommended as first line sedative agent in ventilated cardiogenic shock patients, although data regarding the optimal sedation strategy are sparse. The aim of this study was to investigate the hemodynamic effects of propofol versus midazolam sedation in our cardiogenic shock registry. Mechanically ventilated patients suffering from cardiogenic shock were retrospectively enrolled from the cardiogenic shock registry of the university hospital of Munich. 174 patients treated predominantly with propofol were matched by propensity-score to 174 patients treated predominantly with midazolam. Catecholamine doses were similar on admission but significantly lower in the propofol group on days 1-4 of ICU stay. Mortality rate was 38% in the propofol and 52% in the midazolam group after 30 days (p = 0.002). Rate of ≥BARC3 bleeding was significantly lower in the propofol group compared to the midazolam group (p = 0.008). Sedation with midazolam was significantly associated with ICU mortality. In this observational cohort study, sedation with propofol in comparison to midazolam was linked to a reduced dose of catecholamines, decreased mortality and bleeding rates for patients with cardiogenic shock. Based on this study and in contrast to current recommendations, propofol should be given consideration for sedation in cardiogenic shock patients.