Risk Factors, Clinical Presentation, Therapeutic Trends, and Outcomes in Arterial Thrombosis Complicating Unvaccinated COVID-19 Patients: A Systematic Review.

Data on characteristics and outcomes of coronavirus (COVID)-19 patients complicated with arterial thrombosis (AT) are scarce. Therefore, we carried out a systematic review (PRISMA, PROSPERO statements; PubMed, Scopus, and Web of Science) to identify risk factors, clinical presentation, treatment, and outcomes. We included publications from December 2019 to October 2020. Groups: (a) ischemic stroke, (b) thrombotic storm, (c) peripheral vascular thrombosis, (d) myocardial infarction, and (e) left cardiac thrombus or in-transit thrombus (venous system thrombus floating or attaching to the right heart). We considered 131 studies. The most frequent cardiovascular risk factors were: hypertension, diabetes, and dyslipidemia. A high proportion presented with asymptomatic, mild, or moderate COVID-19 (n = 91, 41.4%). We identified a high percentage of isolated ischemic stroke and thrombotic storm. Groups with higher mortality rate: intracardiac thrombus (1/2, 50.0%), thrombotic storm (18/49, 36.7%), and ischemic stroke (48/131, 36.6%). A small number received thromboprophylaxis. Most patients received antithrombotic treatment. The most frequent bleeding complication was intracranial hemorrhage, primarily with isolated stroke. Overall mortality was 33.6% (74/220). Despite a wide range of COVID-19 severity, a high proportion had AT as a complication of non-severe disease. AT can affect different vascular territories; mortality is associated with stroke, intensive care unit stay, and severe COVID-19.

Differences between surviving and non-surviving venous thromboembolism COVID-19 patients: a systematic review.

BACKGROUND: To our knowledge, the treatment, outcome, clinical presentation, risk stratification of patients with venous thromboembolism and COVID-19 have not been well characterized. METHODS: We searched for systematic reviews, cohorts, case series, case reports, editor letters, and venous thromboembolism COVID-19 patients' abstracts following PRISMA and PROSPERO statements. We analyzed therapeutic approaches and clinical outcomes of venous thromboembolism COVID-19 patients. Inclusion: COVID-19 patients with venous thromboembolism confirmed by an imaging method (venous doppler ultrasound, ventilation-perfusion lung scan, computed tomography pulmonary angiogram, pulmonary angiography). We assessed and reported the original Pulmonary Embolism Severity Index for each pulmonary embolism patient. In addition, we defined major bleedings according to the International Society of Thrombosis and Haemostasis criteria. RESULTS: We performed a systematic review from August 9 to August 30, 2020. We collected 1,535 papers from PubMed, Scopus, Web of Science, Wiley, and Opengrey. We extracted data from 89 studies that describe 143 patients. Unfractionated and low-molecular-weight heparin was used as parenteral anticoagulation in 85/143 (59%) cases. The Food and Drug Administration-approved alteplase regimen guided the advanced treatment in 39/143 (27%) patients. The mortality was high (21.6%, CI 95% 15.2-29.3). The incidence of major bleeding complications was 1 (0.9%) in the survival group and 1 (3.2%) in the death group. Pulmonary Embolism Severity Index was class I in 11.6% and II in 22.3% in survivors compared to 0% and 6.5% in non-survivors, respectively. Patients who experienced venous thromboembolism events at home were more likely to live than in-hospital events. CONCLUSIONS: We determined a high mortality incidence of pulmonary embolism and a low rate of bleeding. Unfractionated and low-molecular-weight heparin drove parenteral anticoagulation and alteplase the advanced treatment in both groups. The original Pulmonary Embolism Severity Index could be helpful in the risk stratification.

Clinical outcomes of very elderly patients treated with ultrasound-assisted catheter-directed thrombolysis for pulmonary embolism: a systematic review.

Pulmonary embolism (PE) is a significant cause of death in the very elderly (≥ 75 years) population. Ultrasound-assisted catheter-directed thrombolysis (USCDT) emerges to improve thrombolysis safety and efficacy. However, outcomes in very elderly patients are unknown, as randomized controlled trials exclude this population. Recently, we demonstrated acute kidney injury (AKI) and ischemic hepatitis in an octogenarian intermediate-risk PE patient treated with USCDT. Considering the lack of evidence, we undertook a systematic review to evaluate the clinical outcomes in very elderly PE patients treated with USCDT. We searched for very elderly PE patients treated with USCDT from 2008 to 2019. Additionally, we conducted another systematic review without age restriction to update previous evidence and compare both populations. We also did an exploratory analysis to determine if thrombolysis was followed based on current guidelines or impending clinical deterioration factors. We identified 18 very elderly patients (age 79.2, 75-86), mostly female and with intermediate-risk PE. We found an intracranial hemorrhage (ICH), and a right pulmonary artery rupture. Additionally, two significant bleedings complicated with transient AKI, and one case of AKI and ischemic hepatic injury. The patients who survived all had clinical and echocardiographic in-hospital improvement. Despite low rt-PA doses, ICH and major bleeding remain as feared complications. Thrombolysis decision was driven by impending clinical deterioration factors instead of international guideline recommendations. Our data do not suggest prohibitive risk associated with USCDT in very elderly intermediate and high-risk PE patients. Despite long-term infusions and right ventricular dysfunction, AKI and ischemic hepatic injury were infrequent.

Thrombolysis in massive and submassive pulmonary embolism during pregnancy and the puerperium: a systematic review.

Thrombolysis in high-risk pulmonary embolism (PE) patients is recommended worldwide; however, the evidence for thrombolysis during pregnancy and the immediate puerperium remains unclear. We conducted a systematic review from 1950 to 2019 through PubMed, Ovid/Willey, and Cochrane Library to assess the safety and effectiveness of thrombolysis during pregnancy and the immediate puerperium. Additionally, we characterized the clinical presentation, risk stratification, and diagnostic approach. We have communicated our results according to the PRISMA statement. We collected 141 records and, after critical assessment, included 47 case reports of 54 patients, including 43 and 11 patients during pregnancy and puerperium, respectively. During pregnancy, alteplase was the most frequent systemic thrombolytic agent used (67%), but only nine patients received the approved FDA regimen. With catheter-directed thrombolysis, low-dose thrombolytics and fragmentation were the most common regimens. Major bleeding occurred in 18% of cases, but there was no intracranial bleeding. One maternal death occurred secondary to refractory cardiogenic shock. Fetal mortality was 20%. During the immediate puerperium, nine patients received "off-label" first-, second-, and third-generation thrombolytic regimens, and four cases underwent catheter-directed thrombolysis. We observed nine major bleeding events, seven of which were from the uterine location and none of which were intracranial. In conclusion, overall, these data do not suggest prohibitive risk associated with thrombolysis for PE in pregnancy. Management of massive and high-risk submassive PE in pregnancy should be individualized to each patient. In the data presented, no fatal bleeding or intracranial bleeding was observed. Finally, future efforts should systematically collect and report data on high-risk PE in pregnancy and peripartum patients to improve the evidence-base clinical practice.

The Hospital Zambrano Hellion venous thromboembolism rapid response team (PREVENTION-team): Improving pulmonary embolism and deep venous thrombosis patient care / Equipo de respuesta rápida para tromboembolismo venoso del Hospital Zambrano Hellion (PREVENTION-Team): Mejorando el manejo del tromboembolismo pulmonar y trombosis venosa profunda

Abstract Background: Fast-track worldwide reperfusion programs improve outcomes in ST-elevation myocardial infarction and stroke. Similar programs called Program Evaluation and Review Technique (PERT) focus on submassive and massive pulmonary embolism (PE) excluding deep venous thrombosis (DVT). Methods: PREVENTION-team (Hospital Zambrano Hellion Venous Thromboembolism [VTE] Rapid Response). Primary objective: Fast-track stratification, diagnostics, and treatment (60-90 min) to improve proximal DVT and submassive and massive PE patients care. Secondary objectives: Increase diagnosis rate of low-risk PE and distal DVT; exploration of cause; long-term anticoagulation; identify high-risk profile for chronic complications; community-based support groups and patient education to extend the concept of the thrombosis-free hospital to thrombosis-free home. Structure and organization: The team includes cardiologists, vascular medicine, angiologist, echocardiographer, cardiovascular imaging, and interventional cardiologists. The team will be accessible 24 h a day, 7 days a week, 365 days a year, and base on previous national experience. The cardiology fellow on call will be responsible for activation and evaluation. We will design several tools to accelerate these processes. Risk stratification and therapeutic approach will be based on clinical presentation, echocardiogram, and biomarkers findings. According to PERT stratification based on resources and medical specialties, Hospital Zambrano Hellion has level 1 PERT. PREVENTION-team links physicians with different expertise, provide fast, efficient, and time-saving treatment, potentially saving lives and reducing bleeding and chronic complications in VTE patients. Finally, establishing a network in our hospital and health system to improve VTE patients care. To the best of our knowledge, this is the first rapid response team focused on VTE in Mexico.

Resumen Antecedentes: Programas de reperfusión mejoraron la evolución en infarto con elevación del ST y accidente cerebrovascular embólico. Programas similares llamados PERT para TEP masiva o submasiva excluyen TVP. Métodos: Equipo PREVENTION (Hospital Zambrano Hellion Venous Thromboembolism Rapid Response). Objetivo primario: Estratificación, diagnóstico y tratamiento acelerado (60-90 minutos) para mejorar atención del TVP proximal y TEP masiva o submasiva. Objetivos secundarios: Incrementar diagnóstico de TEP de riesgo bajo y TVP distal; explorar causa; anticoagulación a largo plazo; perfil de riesgo alto para complicaciones crónicas; grupos de soporte en la comunidad y educación para pacientes, y extender el concepto de hospital libre de trombosis a hogar libre de trombosis. Estructura y organización: Incluye cardiólogos, medicina vascular, angiólogo, ecocardiografistas, imagen cardiovascular. Basado en experiencia nacional, el equipo estará accesible 24 horas del día, siete días de la semana, 365 días del año. El residente de cardiología realizará la activación y estratificación. Diseñamos herramientas para acelerar el proceso. La estratificación de riesgo y el abordaje terapéutico se basará en presentación clínica, hallazgos ecocardiograficos y biomarcadores. El Hospital Zambrano Hellion tiene nivel PERT 1 de acuerdo a la estratificación PERT basada en recursos y especialidades. Equipo-PREVENTION en TEV vincula médicos con diferentes capacidades, ofrece rápido y eficiente tratamiento para preservar vidas y reducir complicaciones hemorrágicas y crónicas. En nuestro hospital y sistema de salud establecer una sólida red de trabajo para mejorar la atención. Hasta nuestro conocimiento, en México este podría ser el primer equipo de respuesta rápida enfocado en TEV.

The Hospital Zambrano Hellion venous thromboembolism rapid response team (PREVENTION-team): Improving pulmonary embolism and deep venous thrombosis patient care.

Background: Fast-track worldwide reperfusion programs improve outcomes in ST-elevation myocardial infarction and stroke. Similar programs called Program Evaluation and Review Technique (PERT) focus on submassive and massive pulmonary embolism (PE) excluding deep venous thrombosis (DVT). Methods: PREVENTION-team (Hospital Zambrano Hellion Venous Thromboembolism [VTE] Rapid Response). Primary objective: Fast-track stratification, diagnostics, and treatment (60-90 min) to improve proximal DVT and submassive and massive PE patients care. Secondary objectives: Increase diagnosis rate of low-risk PE and distal DVT; exploration of cause; long-term anticoagulation; identify high-risk profile for chronic complications; community-based support groups and patient education to extend the concept of the thrombosis-free hospital to thrombosis-free home. Structure and organization: The team includes cardiologists, vascular medicine, angiologist, echocardiographer, cardiovascular imaging, and interventional cardiologists. The team will be accessible 24 h a day, 7 days a week, 365 days a year, and base on previous national experience. The cardiology fellow on call will be responsible for activation and evaluation. We will design several tools to accelerate these processes. Risk stratification and therapeutic approach will be based on clinical presentation, echocardiogram, and biomarkers findings. According to PERT stratification based on resources and medical specialties, Hospital Zambrano Hellion has level 1 PERT. PREVENTION-team links physicians with different expertise, provide fast, efficient, and time-saving treatment, potentially saving lives and reducing bleeding and -chronic complications in VTE patients. Finally, establishing a network in our hospital and health system to improve VTE patients care. To the best of our knowledge, this is the first rapid response team focused on VTE in Mexico.

Antecedentes: Programas de reperfusión mejoraron la evolución en infarto con elevación del ST y accidente cerebrovascular embólico. Programas similares llamados PERT para TEP masiva o submasiva excluyen TVP. Métodos: Equipo PREVENTION (Hospital Zambrano Hellion Venous Thromboembolism Rapid Response). Objetivo primario: Estratificación, diagnóstico y tratamiento acelerado (60-90 minutos) para mejorar atención del TVP proximal y TEP masiva o submasiva. Objetivos secundarios: Incrementar diagnóstico de TEP de riesgo bajo y TVP distal; explorar causa; anticoagulación a largo plazo; perfil de riesgo alto para complicaciones crónicas; grupos de soporte en la comunidad y educación para pacientes, y extender el concepto de hospital libre de trombosis a hogar libre de trombosis. Estructura y organización: Incluye cardiólogos, medicina vascular, angiólogo, ecocardiografistas, imagen cardiovascular. Basado en experiencia nacional, el equipo estará accesible 24 horas del día, siete días de la semana, 365 días del año. El residente de cardiología realizará la activación y estratificación. Diseñamos herramientas para acelerar el proceso. La estratificación de riesgo y el abordaje terapéutico se basará en presentación clínica, hallazgos ecocardiograficos y biomarcadores. El Hospital Zambrano Hellion tiene nivel PERT 1 de acuerdo a la estratificación PERT basada en recursos y especialidades. Equipo-PREVENTION en TEV vincula médicos con diferentes capacidades, ofrece rápido y eficiente tratamiento para preservar vidas y reducir complicaciones hemorrágicas y crónicas. En nuestro hospital y sistema de salud establecer una sólida red de trabajo para mejorar la atención. Hasta nuestro conocimiento, en México este podría ser el primer equipo de respuesta rápida enfocado en TEV.

Phase II clinical trial testing the safety of a humanised monoclonal antibody anti-CD20 in patients with heart failure with reduced ejection fraction, ICFEr-RITU2: study protocol.

INTRODUCTION: Chronic heart failure with reduced ejection fraction (HFrEF) treatment targets neurohormonal inhibition; however, our experimental observations and the recent clinical evidence in myocardial infarction and heart transplant patients support the anti-inflammatory pathway as a potential novel therapeutic target. Therefore, we aimed to assess the safety of human monoclonal antibody-CD20 (rituximab) in patients with HFrEF. METHODS AND ANALYSIS: We designed this protocol according to the Standard Protocol Items: Recommendations for Interventional Trials guidelines as a phase II, single-centred, single group and prospective clinical trial. We hypothesise that the use of a monoclonal antibody, rituximab, could be a potentially safe new agent in HFrEF management. We will include patients with EF≤40%, New York Heart Association functional class III/IV and unresponsive to standard treatment. We will use a dosing regimen (1000 mg) previously applied to post-transplant patients and patients with rheumatoid arthritis with favourable results, aiming to provide supplementary evidence of safety in patients with HFrEF. We designed strategies tailored to preserving the integrity of patient safety. The date of study initiation will be 29th of May 2019. ETHICS AND DISSEMINATION: The following protocol was approved by IRB committees, and as a requirement, all patients need to sign an informed consent form before being subjected to any procedure prior to the initiation of the study. We are aware that the trial will be run in patients who due to their cardiovascular functional class, have reserved prognosis, with no known therapy that leads to improvement. Hence, this trial searches to establish the safety of an alternative strategy in ameliorating prognosis. Regardless of the study outcomes, whether favourable or not, they will be published. If a favourable outcome is evidenced, it will prompt performing a phase III, efficacy-based study. TRIAL REGISTRATION NUMBER: The trial was approved by the IRB (CONBIOÉTICA-19-CEI-011-20161017 and COFEPRIS-17-CI-19-039-003), and registered at Clinicaltrials.gov (NCT03332888; Pre-Results).

Factor Xa inhibition and sPESI failure in intermediate-high-risk pulmonary embolism.

We report the case of a 61-year-old man who presented at the Emergency Department (ED), complaining of sudden-onset dyspnea and chest pain after a long flight from Tokyo to Houston. Considering his clinical stability and sPESI 0, enoxaparin 1 mg/kg BID was started for 24 h, and the patient was then considered for early discharge with apixaban 10 mg BID. Direct-factor Xa inhibition did not improve extensive thrombus burden and right ventricular dysfunction despite D-dimer measurement reduction. Because of the treatment failure, we considered thrombolysis. Currently, recommendations to use thrombolysis in patients under non-vitamin K antagonist oral anticoagulants (NOACs) do not exist. Hence, the one dose of apixaban was stopped, and 12 h later, we performed successful thrombolysis. A systematic review from 2007 to 2017 did not identify any cases related to NOACs failure to reduce thrombus burdens in patients with PE and persistent right ventricular dysfunction. We also did not find any evidence of cases that reported strategies for urgent thrombolysis in PE patients on NOACs. To the best of our knowledge, apixaban's failure to reduce thrombus burden, persistent right ventricular dysfunction, and a NOACs-thrombolysis bridge in patients with PE on apixaban has not been previously described. Both the bedside risk stratification and the therapeutic failures should alert clinicians in the ED to the potential limitations of low-molecular-weight heparin, NOACs therapy, and sPESI in the setting of intermediate-high-risk PE.