Higher Bleeding Rates Research Articles

Direct oral anticoagulants compared to vitamin K antagonists for the treatment of left ventricular thrombi

Abstract Background Left ventricular thrombus (LVT) complicates around one in six cases of acute and chronic left ventricular systolic dysfunction and is associated with an increased risk of stroke, major systemic embolism and death, believed to be ameliorated by anticoagulation. Off-label use of direct oral anticoagulants (DOACs) for LVT has steadily increased, largely based on favourable outcomes in atrial fibrillation and venous thromboembolism, but the safety and efficacy of DOACs versus vitamin K antagonists (VKA) for LVT remains uncertain. Purpose The main aim of our study was to compare treatment of LVT with VKA to DOAC, focusing on all-cause mortality, stroke, major systemic emboli and major bleeding. Methods We conducted a retrospective observational longitudinal study of patients presenting to two large quaternary centres between 2011 and 2021 with a diagnosis of LVT. Patients were eligible if they had a documented LVT and received anticoagulation with either VKA or DOAC. Baseline data, thrombus characteristics, treatment type and duration, follow up imaging and clinical events were recorded using electronic health care records. Outcome measures included thrombus resolution, stroke and systemic embolism (SSE), major bleeding and mortality. Results A total of 955 patients were identified, of whom 901 received treatment with either a VKA (567 pts, 62.9%) or a DOAC (334 pts, 37.1%) and were included in the analysis. Underlying aetiologies included acute myocardial infarction (AMI) (38.3%), chronic ischaemic cardiomyopathy (38.0%) and non-ischaemic cardiomyopathy (23.7%). Rivaroxaban (43.4%) was the most frequently prescribed DOAC followed by apixaban (35.9%), and the remaining on edoxaban (20.7%). AMI related LVT was more commonly treated with DOAC (53.0%) and chronic ischaemic cardiomyopathy with VKA (72.9%). There was a lower baseline LVEF in the VKA cohort (29.5±13.2 vs 33.1±14.2, p<0.0001). Other demographic features were comparable. Median follow up was 2.5 years (IQR: 1–3.5). There were no differences in follow up duration between the two treatments (p=0.17). Greater rates of thrombus resolution were seen in the DOAC group compared to VKA (1 year: 78.4% vs 51.4%, p<0.0001), with higher rates of persistent thrombus over the follow-up period seen in the VKA group (25.1% vs 12.9%, p<0.0001). Rates of stroke and systemic embolization were similar between the groups (VKA 9.3% vs 9.6% DOAC, p=0.93). Higher rates of bleeding (BARC >3, 8.1% VKA, 3.6% DOAC, p=0.031) (Figure 1A) and mortality (VKA 18.5%, DOAC 10.2%, p=0.001) (Figure 1B) were seen in the VKA group over the follow-up period. Conclusions In a large multi-centre registry of LVT of mixed aetiology, anticoagulation with DOAC was associated with earlier and greater rates of thrombus resolution and consequential reduced adverse events (major bleeding and mortality) during follow up. A funding application to support a multi-centre randomised control trial is underway. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by the British Heart Foundation (Fellowship FS/CRTF/21/24190 to HM) and the National Institute for Health Research (Biomedical Research Centre Award to Guy's and St Thomas' NHS FT and King's College London).

Early in-hospital discontinuation of aspirin following coronary stent implantation in patients with indication for direct oral anticoagulation

Abstract Background and purpose 5–10% of patients undergoing percutaneous coronary intervention (PCI) have an indication for oral anticoagulation (OAC). Triple therapy, i.e. anticoagulation plus dual antiplatelet therapy, is associated with a high bleeding rate. Discontinuation of aspirin while continuing direct OAC (DOAC) and a P2Y12 inhibitor (so-called dual therapy) after PCI, was investigated in four randomized trials demonstrating a reduction in bleeding without significant differences in ischemic events. Since randomization was performed several days after the index PCI, these trials allowed for a short period of triple therapy. Whether exclusive procedural application of aspirin and early discontinuation of aspirin at the first postprocedural day is safe, is unknown and was the scope of this work. Methods and results We retrospectively analysed 3613 patients (4564 PCIs) treated from 2017 to 2020 at our centre. 871 (24.1%) patients (1059 PCIs, 23.2%) had an indication for OAC. In 284 PCIs with stenting, patients received DOAC (71.8% Rivaroxaban, 25.7% Apixaban, 1.8% Dabigatran, 0.7% Edoxaban) + P2Y12 inhibitor (100% clopidogrel) + aspirin only at the day of procedure (group 1). In 52 PCIs with stenting, patients received DOAC (59.6% Rivaroxaban, 34.6% Apixaban, 1.9% Dabigatran, 3.9% Edoxaban) + P2Y12 inhibitor (100% clopidogrel) + 100 mg aspirin/d at ≥1 postprocedural day (group 2). Based on our local patient database, we analysed the rate of ischemic events (myocardial infarction, stent thrombosis, stroke/transient ischemic attack (TIA), pulmonary/systemic embolism (PE/SE), deep vein thrombosis) as well as major and minor bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) criteria during hospitalisation. Data are presented as mean±standard deviation or median (range). Baseline characteristics were similar (group 1 vs. group 2: 74.3% vs. 73.1% male, age 75.9±8.5 vs. 74.3±9.3 years, atrial fibrillation 91.2% vs. 88.5%), except previous PE (3.5% vs. 11.5%; p=0.024), type of preprocedural DOAC (Rivaroxaban 52.5% vs. 34.6%; p=0.023) and creatinine clearance (62.4±19.7 vs. 68.9±20.3 ml/min; p=0.029). Median duration of postprocedural hospitalisation was 1 day for both groups (0–20 days vs. 1–21 days). In both groups, one TIA occurred (p=0.292), there were no other ischemic events. 36 (12.7%) bleeding events occurred in group 1 and 11 (21.2%) in group 2 (p=0.126). A subgroup analysis of cases being hospitalised for ≥2 postprocedural days (group 1: 87 cases, median 4 (2–20) days; group 2: 20 cases, median 2 (2–21) days) found no ischemic events and no difference regarding bleeding events (34.5% vs. 45.0%; p=0.443). Conclusions Exclusive procedural application of aspirin and start of dual therapy at the first postprocedural day appears safe regarding ischemic events in a real-world population. Nearly ¼ of patients undergoing PCI had an indication for OAC, which is much more frequent than previously reported. Funding Acknowledgement Type of funding sources: None.

Complications After Transthoracic Needle Biopsy of Pulmonary Nodules: A Population-Level Retrospective Cohort Analysis.

To provide recent population-based estimates of transthoracic needle biopsy (TTNB) complications and risk factors associated with these complications. This retrospective cohort analysis included adults from a nationally representative longitudinal insurance claims data set who underwent TTNB in 2017 or 2018. Complications that were evaluated included pneumothorax, hemorrhage, and air embolism. Separate logistic regression models estimated the association of pneumothorax or hemorrhage with the setting of care (ie, inpatient or outpatient) and selected baseline patient demographic and clinical characteristics including age, gender, history of chronic obstructive pulmonary disease, diagnosis of pleural effusion, tobacco use, use of oral anticoagulants and antiplatelet agents, prior lung cancer screening, previous bronchoscopy within 1 year, and Elixhauser comorbidity index. Among 16,971 patients who underwent TTNB, 25.8% experienced a complication within 3 days of the procedure (pneumothorax 23.3%, hemorrhage 3.6%, and air embolism 0.02%). Among patients who experienced pneumothorax, 31.9% required chest tube drainage. Among patients undergoing an outpatient TTNB (n= 12,443), 6.9% were hospitalized within 7 days. Biopsy in an inpatient setting, chronic obstructive pulmonary disease diagnosis, and prior bronchoscopy were associated with higher rates of both pneumothorax and hemorrhage. Prior lung cancer screening was associated with an increased risk of pneumothorax, and prior use of oral anticoagulants or antiplatelets was associated with higher rates of hemorrhage. This contemporary population-based cohort study demonstrated that approximately one-quarter of patients undergoing TTNB experienced a complication. Pneumothorax was the most frequent complication, and hemorrhage and air embolism were rare. Among outpatients, complications from TTNB are an important cause of hospitalization.

WHERE ARE YOU GOING: EMERGENCY MANAGEMENT OF A THROMBUS-IN-TRANSIT WITH PERCUTANEOUS MECHANICAL THROMBECTOMY AT A COMMUNITY HOSPITAL

WHERE ARE YOU GOING: EMERGENCY MANAGEMENT OF A THROMBUS-IN-TRANSIT WITH PERCUTANEOUS MECHANICAL THROMBECTOMY AT A COMMUNITY HOSPITAL

Direct Oral Anticoagulants for the Prevention and Acute Treatment of Cancer-Associated Thrombosis.

Cancer is a major risk factor for venous thromboembolism (VTE), and cancer-associated thrombosis (CAT) constitutes approximately 15–25% of all VTE cases. For decades, the standard treatment for CAT used to be daily subcutaneous low molecular weight heparin (LMWH). Data on the safety and efficacy of the direct oral anticoagulants (DOACs) in this population emerged only in recent years and specific DOACs were included into recent guidelines recommendations. In this narrative review of the literature, we reported the results of the phase III randomized controlled trials that evaluated the DOACs for the prevention and the acute treatment of CAT. For the acute phase treatment, the anti-Xa inhibitors (apixaban, edoxaban, rivaroxaban) showed better efficacy than LMWH in preventing VTE recurrence; however, rivaroxaban and edoxaban were also associated with an increased risk of bleeding events. For primary prevention of CAT in ambulatory cancer patients starting chemotherapy, apixaban and rivaroxaban showed better efficacy than placebo but a trend towards higher bleeding rates. Recent guidelines suggest the DOACs for the treatment of CAT in selected cancer patients (eg, low bleeding risk, no luminal gastrointestinal or genitourinary malignancies, no interfering medications). The DOACs are also suggested for primary thromboprophylaxis in selected ambulatory cancer patients at high risk of VTE (eg, Khorana score ≥2 prior to starting new chemotherapy, low bleeding risk, no interfering medications).

EXTRACORPOREAL MEMBRANE OXYGENATION: A HOPE FOR THE SICKEST PATIENTS WITH COVID-19

EXTRACORPOREAL MEMBRANE OXYGENATION: A HOPE FOR THE SICKEST PATIENTS WITH COVID-19

Reuse of phosphogypsum pretreated with water washing as aggregate for cemented backfill

Phosphogypsum (PG) is reused as aggregate in the cemented backfill, which effectively improves the PG reutilization efficiency. However, the massive impurities contained in aggregate PG would adversely affect the hydration of binder, and therefore deteriorate the strength development of backfill. This research starts with the feasibility study on pretreating PG with the water washing method. Based on the most economical principle of the water demand, the optimal conditions for washing PG were determined at a stirring time of 5 min and a solid–liquid ratio of 1:0.5. Then, the original and pretreated PG were made into the backfill. Compared to using the original PG, the backfill slurry using the pretreated PG had better fluidity performance, such as the lower slurry viscosity and the higher bleeding rate. Furthermore, with the pretreated aggregate PG, the backfill strength was significantly enhanced by more than 8 times. Finally, the environmental behavior of the cemented backfill was investigated. Using the pretreated PG as aggregate, concentrations of PO43− and F− in the bleeding water and backfill leachates could meet the Chinese standard for integrated wastewater discharge. The results extend the reuse of PG as aggregate in a more environmental-friendly way, meeting the needs for sustainable mines.

Rivaroxaban in Rheumatic Heart Disease–Associated Atrial Fibrillation

BackgroundTesting of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease–associated atrial fibrillation has been limited.MethodsWe enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis.ResultsOf 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, −76 days; 95% confidence interval [CI], −121 to −31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, −72 days; 95% CI, −117 to −28). No significant between-group difference in the rate of major bleeding was noted.ConclusionsAmong patients with rheumatic heart disease–associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.)

Predictors of Major Hemorrhage After Spleen Core Biopsy in Cancer Patients

In this retrospective study, 232 spleen biopsies from 218 patients with cancer were assessed. Biopsies resulting in hemorrhage requiring hospitalization, transfusion, or other interventions were compared with those that did not. The maximization of the Youden index helped determine the optimal systolic blood pressure (SBP) and platelet count thresholds. There were 15 (7%) major hemorrhages among 211 core biopsies. A multivariate logistic regression model showed that higher SBP, lower platelet count, and the lack of ultrasound guidance were independently associated with major hemorrhage (P < .05). The optimal SBP cutoff was 140 mm Hg, and the platelet count cutoff was 120,000 platelets/μL. In conclusion, the high major hemorrhage rate of 7% among percutaneous core spleen biopsies in patients with cancer may be mitigated by controlling SBP to <140 mm Hg and avoiding biopsy in patients with thrombocytopenia.

Early Reexploration for Bleeding Is Associated With Improved Outcome in Cardiac Surgery

BackgroundReexploration after cardiac surgery, most frequently for bleeding, is a quality metric used to assess surgical performance. This may cause surgeons to delay return to the operating room in favor of attempting nonoperative management. This study investigated the impact of the timing of reexploration on morbidity and mortality. MethodsThis study was a single-institution retrospective review of all adult cardiac surgery patients from July 2010 to June 2020. Time to reexploration was assessed, and outcomes were compared across increasing time intervals. Reported bleeding sites were classified into 5 groups, and bleeding rate (chest tube output) was compared across bleeding sites. Univariable analysis was performed using the Fisher exact and Kruskal-Wallis tests. Multivariable logistic regression models were used for risk-adjusted analyses. ResultsOf 10 070 eligible patients, 251 (2.5%) required reexploration for postoperative bleeding. The most common site of bleeding was “any suture line” (n = 70; 28%). Interestingly, in 30% of cases (n = 75) “no active bleeding” site was reported. The highest rate of bleeding (mL/h) was observed in the “any mediastinal structure” group (median, 450; interquartile range [IQR], 185, 8878), and the lowest rate was noted in the “no active bleeding” group (median, 151.2; IQR, 102, 270). Both morbidity rates (0-4 hours, 12.3% vs 25-48 hours, 37.5%; P = .001) and mortality rates (0-4 hours, 3.1% vs 25-48 hours, 43.8%; P = .001) escalated significantly with increasing time to reexploration. ConclusionsDelayed reexploration for bleeding after cardiac surgery is associated with increased risk for morbidity and mortality. Early surgical intervention, particularly within 4 hours, may improve outcomes. Implications from using reoperation as a performance metric may lead to unnecessary delay and patient harm.

The effect of BNT162b2 SARS-CoV-2 mRNA vaccine on menstrual cycle symptoms in healthy women.

ObjectiveTo investigate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA BNT162b2 vaccine on women's menstrual cycle.MethodsIn this questionnaire‐based cross‐sectional study, we assessed menstrual pattern and changes in women who completed the SARS‐CoV‐2 mRNA BNT162b2 vaccine 3 months before and after receiving the vaccine. Included were women aged 18–50 years without known gynecologic comorbidities who regularly monitor their menstruation through electronic calendars. All participants competed a detailed questionnaire on their menstrual symptoms including information on any irregular bleeding. To minimize bias, each woman served as a self‐control before and after vaccination. Primary outcome was rate of irregular bleeding following vaccination and secondary outcome was presence of any menstrual change, including irregular bleeding, mood changes, or dysmenorrhea following the vaccine.ResultsA total of 219 women met the inclusion critieria. Of them, 51 (23.3%) experienced irregular bleeding following the vaccine. Almost 40% (n = 83) of study participants reported any menstrual change following vaccination. Parity was positively asssociated with irregular bleeding with 26 (50%) of those suffering from irregular bleeding being multiparous compared with only 53 (31.5%) of women with no irregular bleeding (nulliparous 46% vs 60%, multiparous 50% vs 31%, rest 4% vs 8%, P = 0.049). The presence of medical comorbidities was also significantly higher among patients who experienced irregular bleeding (20.0% vs 6.0%, P = 0.003).ConclusionOur study shows relatively high rates of irregular bleeding and menstrual changes after receiving the SARS‐CoV‐2 mRNA BNT162b2 vaccine. Further research is needed to confirm our findings and to better characterize the magnitude of change and any possible long‐term implications.

A Brief Review of Thrombolytics for Venous Interventions.

Anticoagulation continues to be the mainstay of therapy for the management of venous thromboembolism. However, anticoagulation does not lead to the breakdown or dissolving of the thrombus. In an acute pulmonary embolism, extensive thrombus burden can be associated with a high risk for early decompensation, and in acute deep venous thrombosis, it can be associated with an increased risk for phlegmasia. In addition, residual thrombosis can be associated with chronic thromboembolic pulmonary hypertension and postthrombotic syndrome in a chronic setting. Thrombolytic therapy is a crucial therapeutic choice in treating venous thromboembolism for thrombus resolution. Historically, it was administered systemically and was associated with high bleeding rates, particularly major bleeding, including intracranial bleeding. In the last two decades, there has been a significant increase in catheter-based therapies with and without ultrasound, where lower doses of thrombolytic agents are utilized, potentially reducing the risk for major bleeding events and improving the odds of reducing the thrombus burden. In this article, we provide an overview of several thrombolytic therapies, including delivery methods, doses, and outcomes.

Platelet transfusion and anticoagulation in hematological cancer‐associated thrombosis and thrombocytopenia: The CAVEaT multicenter prospective cohort

BackgroundVenous thromboembolism (VTE) in patients with thrombocytopenia represents a complex management challenge. ObjectivesTo describe practice, document outcomes, and compare management to national guidelines. MethodsWe present a prospective multicenter cohort of 105 patients with hematological cancer, VTE within 28 days, and platelets <50 × 109/L from May 14, 2019 to April 24, 2021 from 20 sites. ResultsMedian age was 64 and median initial platelet count 28 × 109/L. Thromboses were: 46% catheter‐associated, 11% lower limb, 33% pulmonary emboli (PE), and 10% other sites. Management was according to International Society on Thrombosis and Haemostasis (ISTH) guidance in 30 (47%) of 64 patients with high‐risk thrombosis and 2 (5%) of low‐risk thrombosis (catheter‐associated or asymptomatic subsegmental PE). Twelve patients (11%) received no anticoagulation. At 28 days mortality was 15%, 8% experienced VTE progression, 7% experienced major bleeding, and 25% experienced clinically relevant non‐major bleeding. Four inferior vena cava filters were placed, two were later removed. The median number of platelet units transfused was 5 (range 0–53). Twenty‐seven percent of patients had a change of management strategy by 28 days. There was no clear relationship among platelet transfusion threshold, anticoagulant dose reduction threshold, and risk of thrombosis progression or major bleeding. ConclusionsThis data set demonstrates the heterogeneity of approaches used in patients presenting with severe thrombocytopenia and acute thrombosis and confirms the high rates of bleeding in this cohort with thrombosis progression rates similar to the wider cancer‐associated thrombosis population. Randomized data is required to inform the optimal management.

Characterization of Biomarkers of Hemostasis and Bleeding-Related Outcomes in Children With Cirrhosis.

We aimed to evaluate differences in laboratory tests, bleeding, transfusions, and thrombosis between (1) children without and with cirrhosis and (2) children and adults with cirrhosis, and to correlate thromboelastography (TEG) parameters with biomarkers of hemostasis, bleeding, and transfusions in children and adults with cirrhosis. This single-center, retrospective study included 20 children without cirrhosis, 40 children with cirrhosis, and 40 adults with cirrhosis who underwent a liver transplant (LT). We collected demographic data, preoperative laboratory values, and intraoperative TEG parameters. Biomarkers of hemostasis just prior to the start of LT surgery were analyzed including international normalized ratio (INR), platelet, fibrinogen level, R time, K time, alpha angle (α), and maximum amplitude (MA). We also collected outcome data including blood loss, transfusion requirements, and thrombosis. A significantly higher proportion of children with cirrhosis had abnormal PT ( P = 0.001), platelet ( P = 0.001), K time ( P = 0.02), and MA ( P = 0.05) compared to children without cirrhosis. The incidences of thrombosis, bleeding events, blood loss or PRBC transfusion were not significantly different between these 2 groups. A significantly higher proportion of adults with cirrhosis had abnormal R time ( P = 0.01) and alpha angle ( P = 0.01) than children with cirrhosis. Children with cirrhosis had defects in fibrinogen and platelets compared to children without cirrhosis at time of LT; however, these abnormalities did not translate into higher rates of bleeding in the former. Adults with cirrhosis had more defects in clotting factors compared to children with cirrhosis.

Incidence and outcomes of thromboembolic and bleeding events in patients with liver cirrhosis in the USA.

Understanding the epidemiology of bleeding and thromboembolism (clotting) in liver cirrhosis provides important data for future studies and policymaking; however, head-to-head comparisons of bleeding and clotting remain limited. This is a populational retrospective cohort study using the US National Readmission Database of 2018 to compare the incidence and outcomes of bleeding and clotting events in patients with liver cirrhosis. The primary outcomes were the 11-month incidence proportion of bleeding and clotting events. Of 1304 815 participants, 26 569 had liver cirrhosis (45.0% women, mean age 57.2 [SD, 12.7] years). During the 11-month follow-up, in patients with cirrhosis, for bleeding and clotting events, the incidence proportions was 15.3% and 6.6%; the risk-standardized all-cause mortality rates were 2.4% and 1.0%; the rates of intensive care intervention were 4.1% and 1.9%; the rates of rehabilitation transfer were .2% and .2%; the cumulative length of stays were 45 100 and 23 566 days; total hospital costs were 147 and 84 million US dollars; total hospital charges were 620 and 365 million US dollars. Compared to non-cirrhosis, liver cirrhosis was associated with higher rates of bleeding (adjusted hazard ratio, 3.02 [95% CI, 2.85-3.20]) and portal vein thrombosis (PVT) (18.46 [14.86-22.92]), and slightly lower risks of other non-PVT venous thromboembolic events (.82 [.75-.89]). Bleeding is more common than thromboembolism in patients with liver cirrhosis, causes higher morbidity, mortality and resource utilization. Liver cirrhosis is an independent risk factor for bleeding and PVT, but not non-PVT thromboembolism including venous thromboembolism, acute myocardial infarction and ischemic stroke.

Natural course of untreated spinal cord cavernous malformations: a follow-up study within the initial 5 years after diagnosis.

Cavernous spinal cord malformations (SCMs) are believed to have a high rate of bleeding. The risk of intramedullary hemorrhage (IMH) or recurrent IMH and the neurological impact of bleeding events are important for clinical decision-making and could impact current treatment strategies. The authors screened their institutional database for patients with cavernous SCM treated between 2003 and 2020. Patients with complete MRI data sets and clinical baseline characteristics were included. Surgically treated patients were censored after cavernous SCM removal. Neurological functional status was obtained using the modified McCormick (MMcC) scale at diagnosis, first IMH, and second IMH. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage or rehemorrhage. Seventy-one patients with cavernous SCM were analyzed. Cox regression analysis identified previous IMH (hazard ratio 7.86, 95% confidence interval 1.01-61.47, p = 0.049) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of bleeding or rebleeding was 41.3% for cavernous SCM. The MMcC score significantly deteriorated in 75% of patients after recurrent hemorrhage (p = 0.012). During untreated 5-year follow-up, a considerably increased risk for hemorrhage or rehemorrhage was found in cavernous malformations of the spinal cord compared to cerebral cavernous malformations. Neurological function significantly deteriorates after the second bleeding. The probability of recurrent IMH increased significantly after initial presentation with hemorrhage.

Apixaban or Warfarin and Aspirin or Placebo After Acute Coronary Syndrome or Percutaneous Coronary Intervention in Patients With Atrial Fibrillation and Prior Stroke

Data are limited regarding the risk of cerebrovascular ischemic events and major bleeding in patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). Determine the efficacy and safety of apixaban or vitamin K antagonists (VKA) and aspirin or placebo according to prior stroke, transient ischemic attack (TIA), or thromboembolism (TE). In this prospective, multicenter, 2-by-2 factorial, randomized clinical trial, post hoc parallel analyses were performed to compare randomized treatment regimens according to presence or absence of prior stroke/TIA/TE using Cox proportional hazards models. Patients with AF, recent ACS or PCI, and planned use of P2Y12 inhibitors for 6 months or longer were included; 33 patients with missing data about prior stroke/TIA/TE were excluded. Apixaban (5 mg or 2.5 mg twice daily) or VKA and aspirin or placebo. Major or clinically relevant nonmajor (CRNM) bleeding. Of 4581 patients included, 633 (13.8%) had prior stroke/TIA/TE. Patients with vs without prior stroke/TIA/TE were older; had higher CHA2DS2-VASC and HAS-BLED scores; and more frequently had prior bleeding, heart failure, diabetes, and prior oral anticoagulant use. Apixaban was associated with lower rates of major or CRNM bleeding and death or hospitalization than VKA in patients with (hazard ratio [HR], 0.69; 95% CI, 0.46-1.03) and without (HR, 0.68; 95% CI, 0.57-0.82) prior stroke/TIA/TE. Patients without prior stroke/TIA/TE receiving aspirin vs placebo had higher rates of bleeding; this difference appeared less substantial among patients with prior stroke/TIA/TE (P = .01 for interaction). Aspirin was associated with numerically lower rates of death or ischemic events than placebo in patients with (HR, 0.71; 95% CI, 0.42-1.20) and without (HR, 0.93; 95% CI, 0.72-1.21) prior stroke/TIA/TE (not statistically significant). The safety and efficacy of apixaban compared with VKA was consistent with the AUGUSTUS findings, irrespective of prior stroke/TIA/TE. Aspirin increased major or CRNM bleeding, particularly in patients without prior stroke/TIA/TE. Although aspirin may have some benefit in patients with prior stroke, our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for the majority of patients with AF and ACS and/or PCI, regardless of prior stroke/TIA/TE status. ClinicalTrials.gov Identifier: NCT02415400.

Venous thromboembolism (VTE) prevention and diagnosis in COVID-19: Practice patterns and outcomes at 33 hospitals.

BackgroundEarly reports of increased thrombosis risk with SARS-CoV-2 infection led to changes in venous thromboembolism (VTE) management. Real-world data on the prevalence, efficacy and harms of these changes informs best practices.ObjectiveDefine practice patterns and clinical outcomes related to VTE diagnosis, prevention, and management in hospitalized patients with coronavirus disease-19 (COVID-19) using a multi-hospital US sample.MethodsIn this retrospective cross-sectional study of 1121 patients admitted to 33 hospitals, exposure was dose of anticoagulant prescribed for VTE prophylaxis (standard, intensified, therapeutic), and primary outcome was VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]); secondary outcomes were PE, DVT, arterial thromboembolism (ATE), and bleeding events. Multivariable logistic regression models accounting for clustering by site and adjusted for risk factors were used to estimate odds ratios (ORs). Inverse probability weighting was used to account for confounding by indication.Results1121 patients (mean age 60 ± 18, 47% female) admitted with COVID-19 between February 2, 2020 and December 31, 2020 to 33 US hospitals were included. Pharmacologic VTE prophylaxis was prescribed in 86%. Forty-seven patients (4.2%) had PE, 51 (4.6%) had DVT, and 23 (2.1%) had ATE. Forty-six patients (4.1%) had major bleeding and 46 (4.1%) had clinically relevant non-major bleeding. Compared to standard prophylaxis, adjusted odds of VTE were 0.67 (95% CI 0.21–2.1) with no prophylaxis, 1.0 (95% CI 0.06–17) with intensified, and 3.0 (95% CI 0.89–10) with therapeutic. Adjusted odds of bleeding with no prophylaxis were 5.6 (95% CI 3.0–11) and 5.3 (95% CI 3.0–10) with therapeutic (no events on intensified dosing).ConclusionsTherapeutic anticoagulation was associated with a 3-fold increased odds of VTE and 5-fold increased odds of bleeding. While higher bleeding rates with high-intensity prophylaxis were likely due to full-dose anticoagulation, we conclude that high thrombosis rates were due to clinical concern for thrombosis before formal diagnosis.

Effect of anti-platelet therapy on peri-operative blood loss in patients undergoing off-pump coronary artery bypass grafting.

Purpose:The purpose of this study was to review the effect of the pre-operative use of clopidogrel and aspirin on peri-operative bleeding, blood product transfusion, and resource utilization after coronary artery bypass grafting (CABG).Materials and Methods:A total of 1200 patients who underwent off-pump CABG (OPCABG) between 2010 and 2012 were retrospectively studied. Patients were divided into three groups: group 1: discontinued aspirin and clopidogrel 6 days prior to surgery (n = 468), group 2: discontinued both drugs 3 to 5 days prior to surgery (n = 621), and group 3: discontinued both drugs 2 days prior to surgery (n = 111). The bleeding pattern and blood product transfusion were studied and compared between the groups. Patients having history of other drugs affecting the coagulation profile, other organ dysfunction, on-pump CABG, and the combined procedure were excluded from the study.Results:Group 2 patients had a higher rate of bleeding and a reduced mean value of hemoglobin (Hb) as compared to other groups. The same results were seen in blood and blood product transfusion. Patients of group 2 and group 3 were associated with higher blood loss in terms of drainage at 12 and 24 hours. Post-operatively, this was statistically significant. Re-exploration was statisitically significant in group 3 patients (9.01%) than in group 2 (2.58%) and group 1 (1.07%) patients.Conclusion:The pre-operative use of clopidogrel and aspirin in patients undergoing OPCABG showed limited clinical benefits; however, its use significantly increased the risk of bleeding and blood transfusion, thus increasing morbidity and resource utilization. Hence, clopidogrel and aspirin should be stopped at least 6 days prior to surgery.

Age as a Risk Factor in the Occurrence of Complications during or after Bronchoscopic Lung Biopsy.

Introduction: Bronchoscopic lung biopsy (BLB) is a widely used procedure. As the world’s population is ageing, more BLBs are performed for older people with comorbidities. The aim of the study was to investigate if an older age is a risk factor for BLB related complications. Materials and Methods: A prospective study at the Centre of Pulmonology and Allergology of Vilnius University Hospital Santaros klinikos was conducted. Seven hundred and eighty-six patients (male 60.6%), mean age 57 ± 16, who underwent BLB, were included. The complications that occurred due to BLB were evaluated. Bleeding and pneumothorax were classified into I° or II° grades depending on their severity. Potential determinants, which may increase the risk of complications, emphasizing on age, were analyzed. Results: Fifty-seven (7.2%) BLB-related complications occurred. There were 27 (3.4%) pneumothoraxes, and 19 (70%) of them required thoracic drainage. Thirty (3.8%) bleeding complications occurred, and four (16%) of them were severe. Higher rates of bleeding were found in the age group ≥65 years, p = 0.001. The risk of bleeding in older patients was 3.2 times higher (95% CI 1.51–6.87). Conclusions: Older age is related to a higher incidence of mild bleeding during BLB. However, the risk of life-threatening complications is low despite the age, and older age should not be considered as a contraindication for the procedure if needed.