Randomised controlled trial of a prognostic assessment and management pathway to reduce the length of hospital stay in normotensive patients with acute pulmonary embolism.

BACKGROUND: The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown. METHODS: We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes. RESULTS: Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7-4.2 days) in the intervention group and 6.1 days (IQR 5.7-6.5 days) in the control group (p<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR -58.37, 95% CI EUR -84.34- to -32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR -1147.31, 95% CI EUR -1414.97- to -879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates. CONCLUSIONS: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.

Survival and quality of life after early discharge in low-risk pulmonary embolism.

INTRODUCTION: Early discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes. METHODS: The multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire) and generic (five-level five-dimension EuroQoL (EQ-5D-5L) scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale (ACTS)) after pulmonary embolism. RESULTS: The primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The 1-year mortality was 2.4%. The mean±sd PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. The EQ-5D-5L was 0.89±0.12 at 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 points at 3 months (p<0.0001). CONCLUSIONS: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.

AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes in Patients Hospitalized for COPD Exacerbation: A Randomized Clinical Trial.

Importance: Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD). Objective: To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation. Design, Setting, and Participants: Randomized clinical trial conducted across 18 hospitals in Spain. A total of 746 patients were randomized from September 2014 to July 2020 (final follow-up was November 2020). Interventions: Usual care plus an active strategy for diagnosing PE (D-dimer testing and, if positive, computed tomography pulmonary angiogram) (n = 370) vs usual care (n = 367). Main Outcomes and Measures: The primary outcome was a composite of nonfatal symptomatic venous thromboembolism (VTE), readmission for COPD, or death within 90 days after randomization. There were 4 secondary outcomes, including nonfatal new or recurrent VTE, readmission for COPD, and death from any cause within 90 days. Adverse events were also collected. Results: Among the 746 patients who were randomized, 737 (98.8%) completed the trial (mean age, 70 years; 195 [26%] women). The primary outcome occurred in 110 patients (29.7%) in the intervention group and 107 patients (29.2%) in the control group (absolute risk difference, 0.5% [95% CI, -6.2% to 7.3%]; relative risk, 1.02 [95% CI, 0.82-1.28]; P = .86). Nonfatal new or recurrent VTE was not significantly different in the 2 groups (0.5% vs 2.5%; risk difference, -2.0% [95% CI, -4.3% to 0.1%]). By day 90, a total of 94 patients (25.4%) in the intervention group and 84 (22.9%) in the control group had been readmitted for exacerbation of COPD (risk difference, 2.5% [95% CI, -3.9% to 8.9%]). Death from any cause occurred in 23 patients (6.2%) in the intervention group and 29 (7.9%) in the control group (risk difference, -1.7% [95% CI, -5.7% to 2.3%]). Major bleeding occurred in 3 patients (0.8%) in the intervention group and 3 patients (0.8%) in the control group (risk difference, 0% [95% CI, -1.9% to 1.8%]; P = .99). Conclusions and Relevance: Among patients hospitalized for an exacerbation of COPD, the addition of an active strategy for the diagnosis of PE to usual care, compared with usual care alone, did not significantly improve a composite health outcome. The study may not have had adequate power to assess individual components of the composite outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02238639.

[Thymoma in a patient with klinefelter syndrome. Case report]. / Síndrome de Klinefelter diagnosticado en un adulto a raíz del estudio de infección respiratoria recurrente y masa mediastínica. Caso clínico.

Klinefelter syndrome (47, XXY in most cases) is a frequently underdiagnosed chromosomal anomaly associated with multiple comorbidities in adult life. Patients with Klinefelter syndrome have a higher risk of cancer. Specifically, these patients have a higher risk for mediastinal germ cell tumors. It is estimated that 8% of male patients with mediastinal tumors have Klinefelter. We report a 42-years-old male who suffered recurrent respiratory infections. During the study, a mediastinal mass was found, whose pathological study disclosed a type B thymoma. The patient had a history of infertility, high stature, gynecomastia, obesity with gynecoid distribution of body fat and testicular atrophy. A karyotype was requested (47, XXY), confirming the diagnosis of Klinefelter syndrome.

Computerised clinical decision support for suspected PE.

This study aimed to determine the effect of an evidence-based clinical decision support (CDS) algorithm on the use and yield of CT pulmonary angiography (CTPA) and on outcomes of patients evaluated in the emergency department (ED) for suspected PE. The study included 1363 consecutive patients evaluated for suspected PE in an ED during 12 months before and 12 months after initiation of CDS use. Introduction of CDS was associated with decreased CTPA use (55% vs 49%; absolute difference (AD), 6.3%; 95% CI 1.0% to 11.6%; p=0.02). The use of CDS was associated with fewer symptomatic venous thromboembolic events during follow-up in patients with an initial negative diagnostic evaluation for PE (0.7% vs 3.2%; AD 2.5%; 95% CI 0.9% to 4.6%; p<0.01).

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial.

BACKGROUND: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. RESEARCH QUESTION: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? STUDY DESIGN AND METHODS: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. RESULTS: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. INTERPRETATION: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04003116; URL: www. CLINICALTRIALS: gov.

Improvement of thrombosis management in patients with cancer: a practical consensus document of recommendations for cancer-associated thrombosis patients' healthcare in Spain.

Cancer patients are at risk of venous thromboembolism (VTE), its recurrence, but also at risk of bleeding while anticoagulated. In addition, cancer therapies have been associated to increased VTE risk. Guidelines for VTE treatment in cancer patients recommend low molecular weight heparins (LMWH) or direct oral anticoagulants (DOAC) for the initial treatment, DOAC for VTE short-term treatment, and LMWH or DOAC for VTE long-term treatment. This consensus article arises from a collaboration between different Spanish experts on cancer-associated thrombosis. It aims to reach an agreement on a practical document of recommendations for action allowing the healthcare homogenization of cancer-associated thrombosis (CAT) patients in Spain considering not only what is known about VTE management in cancer patients but also what is done in Spanish hospitals in the clinical practice. The text summarizes the current knowledge and available evidence on the subject in Spain and provides a series of practical recommendations for CAT management and treatment algorithms to help clinicians to manage CAT over time.

Impact of emergency department management of isolated superficial vein thrombosis of the lower limbs: a secondary analysis of data from the ALTAMIRA study. / Impacto del manejo en urgencias en la evolución de los pacientes con trombosis venosa superficial aislada de miembros inferiores: subanálisis del estudio ALTAMIRA.

OBJECTIVES: To describe the management of superficial vein thrombosis (SVT) of the lower limbs in patients treated in Spanish hospital emergency departments (EDs). To evaluate the impact of ED management of venous thromboembolic complications on outcomes and to determine the characteristics of patients who develop complications. MATERIAL AND METHODS: The retrospective multicenter ALTAMIRA study (Spanish acronym for risk factors, complications, and assessment of Spanish ED management of SVT) used recorded data for consecutive patients with a diagnosis of isolated SVT treated in 18 EDs. We gathered data on symptomatic venous thromboembolic disease (deep vein thrombosis, pulmonary embolism, or the extension or recurrence of SVT), clinically significant bleeding, and 180-day mortality. Cox regression analysis was used to explore variables associated with complications. RESULTS: A total of 703 patients were included. Anticoagulation was prescribed for 84.1% of the patients for a median of 30 days (interquartile range, 15-42 days); 81.3% were treated with low molecular weight heparin. A prophylactic dose was prescribed for 48% and an intermediate therapeutic dose for 52%. Sixty-four patients (9.2%) developed symptomatic thromboembolic disease within 180 days, 12 (1.7%) experienced clinically significant bleeding, and 4 (0.6%) died. Complications developed later in patients receiving anticoagulant therapy than in those not taking an anticoagulant (66 vs 11 days , P=.009), and 76.6% of those developing complications were not on anticoagulant when symptoms appeared. A history of thromboembolic disease was associated with developing complications (adjusted hazard ratio, 2.20; 95% confidence interval, 1.34-3.62). CONCLUSION: ED treatment of SVT varies and is often suboptimal. The incidence of thromboembolic complications after SVT is high. Starting anticoagulation in the ED delays the development of complications. Patients with a history of thromboembolic disease are more at risk of complications.

OBJETIVO: Describir el manejo terapéutico de los pacientes con trombosis venosa superficial (TVS) aislada de miembros inferiores en servicios de urgencias hospitalarios (SUH) españoles. Evaluar el impacto del tratamiento instaurado en urgencias en la evolución, en términos de complicaciones de enfermedad tromboembólica venosa (ETV), y conocer las características de los pacientes que sufren complicaciones. METODO: El estudio multicentrico (18 SUH) ALTAMIRA (fActores de riesgo, compLicaciones y evaluación del manejo de la TVS de Miembros Inferiores en hospitales españoles atendidos en los seRvicios de urgenciAs) creó un cohorte retrospectivo de pacientes consecutivos con diagnóstico objetivo de TVS aislada. Se recogieron las complicaciones de ETV sintomáticas (trombosis venosa profunda, tromboembolia pulmonar y extensión o recurrencia de TVS), sangrados clínicamente relevantes y defunciones a 180 días. Se evaluaron las variables asociadas a las complicaciones mediante una regresión de Cox. RESULTADOS: Se incluyeron 703 pacientes. El 84,1% recibieron anticoagulación durante 30 días (rango intercuartil 15-42), 81,3% con heparina de bajo peso molecular (48% dosis profilácticas, 52% intermedias-terapéuticas). En 180 días, 64 pacientes (9,1%) tuvieron complicación de ETV, 12 (1,7%) tuvieron sangrado clínicamente relevante, y 4 fallecieron (0,6%). Los pacientes en que se instauró anticoagulación en urgencias tardaron más tiempo en desarrollar complicaciones (66 vs 11 días, p = 0,009). El 76,6% de los que se complicaron no estaban anticoagulados en ese momento. La ETV previa se asoció de forma independiente con el desarrollo de complicaciones (hazard ratio ajustada 2,20; intervalo de confianza del 95%: 1,34-3,62). CONCLUSIONES: El tratamiento en urgencias de la TVS aislada es heterogéneo y con frecuencia subóptimo. La incidencia de complicaciones de ETV es elevada. El tratamiento anticoagulante iniciado en urgencias supone un retraso en el desarrollo de complicaciones. Los pacientes con ETV previa tienen más riesgo de complicaciones.

Heart Rate and Mortality in Patients With Acute Symptomatic Pulmonary Embolism.

BACKGROUND: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. RESEARCH QUESTION: Does an association exist between baseline HR and PE outcome across the continuum of HR values? STUDY DESIGN AND METHODS: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. RESULTS: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. INTERPRETATION: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

Effect of Prognostic Guided Management of Patients With Acute Pulmonary Embolism According to the European Society of Cardiology Risk Stratification Model.

Background: A recent trial showed that management driven by prognostic assessment was effective in reducing the length of stay (LOS) for acute stable pulmonary embolism (PE). The efficacy and safety of this strategy in each subgroup of risk stratification remains unknown. Methods: We conducted a post-hoc analysis of the randomized IPEP study to evaluate the effect of a management strategy guided by early use of a prognostic pathway in the low- and intermediate-high risk subgroups defined by the European Society of Cardiology (ESC) model. These subgroups were retrospectively identified in the control arm. The primary outcome was LOS. The secondary outcomes were 30-day clinical outcomes. Results: Of 249 patients assigned to the intervention group, 60 (24%) were classified as low-, and 30 (12%) as intermediate-high risk. Among 249 patients assigned to the control group, 66 (27%) were low-, and 13 (5%) intermediate-high risk. In the low-risk group, the mean LOS was 2.1 (±0.9) days in the intervention group and 5.3 (±2.9) days in the control group (P < 0.001). In this group, no significant differences were observed in 30-day readmissions (0% vs. 3.0%, respectively), all-cause (0% vs. 0%) and PE-related mortality rates (0% vs. 0%), or severe adverse events (0% vs. 1.5%). In the intermediate-high risk group, the mean LOS was 5.3 (±1.8) days in the intervention group and 6.5 (±2.5) days in the control group (P = 0.08). In this group, no significant differences were observed in 30-day readmissions (3.3% vs. 3.0%, respectively), all-cause (6.7% vs. 7.7%) and PE-related mortality rates (6.7% vs. 7.7%), or severe adverse events (16.7% vs. 15.4%). Conclusion: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE without comprising safety across subgroups of risk stratification. Clinical Trial Registration: [ClinicalTrials.gov], Identifier [NCT02733198].

Outcome of Cancer-Associated Venous Thromboembolism Is More Favorable among Patients with Hematologic Malignancies than in Those with Solid Tumors.

BACKGROUND: The natural history of patients with hematologic cancer and venous thromboembolism (VTE) has not been consistently evaluated. We aimed to compare the rates of symptomatic recurrent VTE, major bleeding, or death during anticoagulant therapy in patients with VTE associated with hematologic versus solid cancers. METHODS: Consecutive patients with active cancer recruited in RIETE were evaluated. Their baseline characteristics, treatments, and outcomes during the course of anticoagulation were compared. Univariate and multivariate competing-risk analyses were performed. RESULTS: As of December 2020, 16,694 patients with cancer and VTE were recruited. Of these, 1,062 (6.4%) had hematologic cancers. Hematologic patients were less likely to initially present with pulmonary embolism (46 vs. 55%) and more likely with upper extremity deep vein thrombosis (25 vs. 18%). They also were more likely to have severe thrombocytopenia at baseline (5.6 vs. 0.7%) or to receive chemotherapy (67 vs. 41%). During the course of anticoagulation (median, 150 vs. 127 days), 1,071 patients (6.4%) developed VTE recurrences, 806 (4.8%) suffered major bleeding, and 4,136 (24.8%) died. Patients with hematologic cancers had lower rates of recurrent VTE (rate ratio [RR]: 0.73; 95% confidence interval [CI]: 0.56-0.95), major bleeding (RR: 0.72; 95% CI: 0.53-0.98), or all-cause death (RR: 0.49; 95% CI: 0.41-0.57) than those with solid cancers. Patients with multiple myeloma showed the best outcomes. CONCLUSION: Patients with hematologic cancers, particularly multiple myeloma, and VTE had better outcomes than those with solid cancers. These findings are relevant for the interpretation of previous clinical trials and the design of future studies.

Multidisciplinary Consensus for the Management of Pulmonary Thromboembolism. / Consenso multidisciplinar para el manejo de la tromboembolia de pulmón.

We have updated recommendations on 12 controversial topics that were published in the 2013 National Consensus on the diagnosis, risk stratification and treatment of patients with pulmonary embolism (PE). A comprehensive review of the literature was performed for each topic, and each recommendation was evaluated in two teleconferences. For diagnosis, we recommend against using the Pulmonary Embolism Rule Out Criteria (PERC) rule as the only test to rule out PE, and we recommend using a D-dimer cutoff adjusted to age to rule out PE. We suggest using computed tomography pulmonary angiogram as the imaging test of choice for the majority of patients with suspected PE. We recommend using direct oral anticoagulants (over vitamin K antagonists) for the vast majority of patients with acute PE, and we suggest using anticoagulation for patients with isolated subsegmental PE. We recommend against inserting an inferior cava filter for the majority of patients with PE, and we recommend using full-dose systemic thrombolytic therapy for PE patients requiring reperfusion. The decision to stop anticoagulants at 3 months or to treat indefinitely mainly depends on the presence (or absence) and type of risk factor for venous thromboembolism, and we recommend against thrombophilia testing to decide duration of anticoagulation. Finally, we suggest against extensive screening for occult cancer in patients with PE.

Therapeutic versus Prophylactic Bemiparin in Hospitalized Patients with Nonsevere COVID-19 Pneumonia (BEMICOP Study): An Open-Label, Multicenter, Randomized, Controlled Trial.

Thromboprophylaxis with low molecular weight heparin in hospitalized patients with COVID-19 is mandatory, unless contraindicated. Given the links between inflammation and thrombosis, the use of higher doses of anticoagulants could improve outcomes. We conducted an open-label, multicenter, randomized, controlled trial in adult patients hospitalized with nonsevere COVID-19 pneumonia and elevated D-dimer. Patients were randomized to therapeutic-dose bemiparin (115 IU/kg daily) versus standard prophylaxis (bemiparin 3,500 IU daily), for 10 days. The primary efficacy outcome was a composite of death, intensive care unit admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress, and venous or arterial thrombosis within 10 days of enrollment. The primary safety outcome was major bleeding (International Society on Thrombosis and Haemostasis criteria). A prespecified interim analysis was performed when 40% of the planned study population was reached. From October 2020 to May 2021, 70 patients were randomized at 5 sites and 65 were included in the primary analysis; 32 patients allocated to therapeutic dose and 33 to standard prophylactic dose. The primary efficacy outcome occurred in 7 patients (22%) in the therapeutic-dose group and 6 patients (18%) in the prophylactic-dose (absolute risk difference 3.6% [95% confidence interval [CI], -16% -24%]; odds ratio 1.26 [95% CI, 0.37-4.26]; p = 0.95). Discharge in the first 10 days was possible in 66 and 79% of patients, respectively. No major bleeding event was registered. Therefore, in patients with COVID-19 hospitalized with nonsevere pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin does not appear to improve clinical outcomes compared with standard prophylactic doses. Trial Registration: ClinicalTrials.gov NCT04604327.

Cancer Histology and Natural History of Patients with Lung Cancer and Venous Thromboembolism.

Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45-214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76-18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09-0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76-1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite.

Estimating Bleeding Risk in Patients with Cancer-Associated Thrombosis: Evaluation of Existing Risk Scores and Development of a New Risk Score.

BACKGROUND: Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice. OBJECTIVES: To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model. METHODS: In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event ("CAT-BLEED"). RESULTS: Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50-0.57; poor calibration). Internal validation of the pragmatic classification and "CAT-BLEED" showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56-0.66, and 0.63; 95% CI 0.58-0.68; good calibration). CONCLUSION: Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with "CAT-BLEED," but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated.

Prediction of Major Bleeding in Anticoagulated Patients for Venous Thromboembolism: Comparison of the RIETE and the VTE-BLEED Scores.

The performance of validated bleeding risk scores in patients with venous thromboembolism (VTE) could be different depending on the time after index event or the site of bleeding. In this study we compared the "classic" Registro Informatizado de Enfermedad TromboEmbólica (RIETE) score and the more recently developed VTE-BLEED score for the prediction of major bleeding in patients under anticoagulant therapy in different time intervals after VTE diagnosis. Out of 82,239 patients with acute VTE, the proportion of high-risk patients according to the RIETE and VTE-BLEED scores was 7.1 and 62.3%, respectively. The performance of both scores across the different study periods (first 30 days after VTE diagnosis, days 31-90, days 91-180, and days 181-360) was similar, with areas under the receiving operating characteristics (ROC) curve (AUC) ranging between 0.69 and 0.72. However, the positive predictive values were low, ranging between 0.6 and 3.9 (better for early major bleeding than for later periods). A sensitivity analysis limited to patients with unprovoked VTE showed comparable results. Both scores showed a trend toward a better prediction of extracranial than intracranial major bleeding, the RIETE score resulting more useful for early extracranial bleeding and the VTE-BLEED for late intracranial hemorrhages. Our study reveals that the usefulness of available bleeding scores may vary depending on the characteristics of the patient population and the time frame evaluated. Dynamic scores could be more useful for this purpose.

Profiles of patients with venous thromboembolic disease in the emergency department and their medium-term prognosis: data from the ESPHERIA registry. / Registro ESPHERIA: perfiles de pacientes con enfermedad tromboembólica venosa en urgencias y su asociación con el pronóstico a medio plazo.

OBJECTIVES: To assess the 180-day prognosis for patients of different profiles diagnosed with venous thromboembolism (VTE) in emergency departments (EDs). Secondary aims were to assess all-cause mortality and readmission rates and to describe the clinical characteristics and forms of presentation of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) in each patient profile. MATERIAL AND METHODS: Secondary analysis of data from the ESPHERIA registry (Spanish acronym for Risk Profile of Patients with VTE Attended in Spanish Emergency Departments), which includes consecutive patients with symptomatic VTE treated in 53 EDs. The cases were divided according to 4 profiles: 1) unprovoked DVT, 2) DVT provoked by transient risk factors, 3)patients with cancer, and 4) patients with low cardiopulmonary reserve. The primary outcome was a composite of 180-day all-cause mortality or readmission. RESULTS: We studied 773 patients: 450 (58.2%) were classified as profile 1, 128 (16.6%) as profile 2, 115 (14.9%) as profile 3 , a nd 8 0 ( 10.3%) a s p rofile 4. We fo und di fferences be tween th e 4 pr ofiles in demographics, com orbidity, clinical presentation, type of DVT and location, management, and outcomes. One hundred ninety-five p atients (25.2%) had at least one of the adverse events included in the composite within 180 days: 69 (8.9%) died and 179 (23.2%) were readmitted. Hazard ratios (HR) indicated that DVT with low cardiopulmonary reserve (HR, 1.73; 95% CI, 1.12-2.68; P = .01)) or DVT with cancer (HR, 3.10; 95% CI, 2.22-4.34; P .001) were the profiles t hat w ere independently associated with the 180-day composite outcome. CONCLUSION: Classifying patients with DVT according to 4 profiles ( unprovoked, provoked by t ransient r isk f actors, associated with cancer, and associated with low cardiopulmonary reserve) when making the diagnosis is useful for assessing prognosis for all-cause mortality or readmission within 180 days. This classification could be useful for establishing a care and follow-up plan when discharging patients with DVT from the ED.

OBJETIVO: Evaluar el pronóstico a 180 días de los pacientes diagnosticados de enfermedad tromboembólica venosa (ETV) en urgencias, en función de una clasificación por perfiles clínicos. Los objetivos secundarios fueron evaluar la mortalidad y el reingreso por todas las causas de manera individual, y describir las características clínicas y formas de presentación de trombosis venosa profunda (TVP) y tromboembolismo pulmonar (TEP), según dichos perfiles. METODO: Análisis secundario del registro ESPHERIA que incluye pacientes consecutivos con ETV sintomática de 53 servicios de urgencias (SU). Se dividió la muestra en 4 perfiles: ETV no provocada (perfil 1), ETV provocada por factores de riesgo transitorios (perfil 2), cáncer (perfil 3) y baja reserva cardiopulmonar (perfil 4). La variable de resultado primaria fue la compuesta mortalidad o reingreso por cualquier causa a 180 días. RESULTADOS: Se incluyeron 773 pacientes de los cuales 450 (58,2%) fueron clasificados en el perfil 1, 128 (16,6%) en el perfil 2, 115 pacientes (14,9%) en el perfil 3 y 80 (10,3%) en el perfil 4. Se documeô€‚˜taron diferencias demográficas, de comorbilidad, presentación clínica, tipo de ETV, manejo, ubicación y resultados entre los perfiles clínicos. Ciento noventa y cinco pacientes (25,2%) presentaron un resultado adverso compuesto a los 180 días, de los cuales 69 (8,9%) fallecieron y 179 (23,2%) sufrieron un nuevo ingreso por cualquier causa. La ETV asociada a baja reserva cardiopulmonar (HR 1,73; IC 95% 1,12-2,68; p = 0,01) y la ETV asociada a cáncer (HR 3,10; IC 95% 2,22-4,34; p 0,001) se asociaron de forma independiente con sufrir un resultado adverso en los primeros 180 días. CONCLUSIONES: Clasificar a los pacientes con ETV según factores de riesgo y comorbilidades en 4 perfiles (no provocada, provocada por factores transitorios, asociada a cáncer y asociada a baja reserva cardiopulmonar) resulta útil al momento del diagnóstico de la ETV para estimar el pronóstico en términos de mortalidad y reingreso a 180 días. Esta clasificación podría ayudar a establecer un plan de cuidados y seguimiento al alta en la ETV diagnosticada en urgencias.

Incidence of VTE and Bleeding Among Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

BACKGROUND: Individual studies have reported widely variable rates for VTE and bleeding among hospitalized patients with coronavirus disease 2019 (COVID-19). RESEARCH QUESTION: What is the incidence of VTE and bleeding among hospitalized patients with COVID-19? METHODS: In this systematic review and meta-analysis, 15 standard sources and COVID-19-specific sources were searched between January 1, 2020, and July 31, 2020, with no restriction according to language. Incidence estimates were pooled by using random effects meta-analyses. Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using the Begg and Egger tests. RESULTS: The pooled incidence was 17.0% (95% CI, 13.4-20.9) for VTE, 12.1% (95% CI, 8.4-16.4) for DVT, 7.1% (95% CI, 5.3-9.1) for pulmonary embolism (PE), 7.8% (95% CI, 2.6-15.3) for bleeding, and 3.9% (95% CI, 1.2-7.9) for major bleeding. In subgroup meta-analyses, the incidence of VTE was higher when assessed according to screening (33.1% vs 9.8% by clinical diagnosis), among patients in the ICU (27.9% vs 7.1% in the ward), in prospective studies (25.5% vs 12.4% in retrospective studies), and with the inclusion of catheter-associated thrombosis/isolated distal DVTs and isolated subsegmental PEs. The highest pooled incidence estimate of bleeding was reported for patients receiving intermediate- or full-dose anticoagulation (21.4%) and the lowest in the only prospective study that assessed bleeding events (2.7%). INTERPRETATION: Among hospitalized patients with COVID-19, the overall estimated pooled incidence of VTE was 17.0%, with higher rates with routine screening, inclusion of distal DVT, and subsegmental PE, in critically ill patients and in prospective studies. Bleeding events were observed in 7.8% of patients and were sensitive to use of escalated doses of anticoagulants and nature of data collection. Additional studies are required to ascertain the significance of various thrombotic events and to identify strategies to improve patient outcomes. TRIAL REGISTRY: PROSPERO; No.: CRD42020198864; URL: https://www.crd.york.ac.uk/prospero/.

Characteristics of isolated superficial vein thrombosis and diagnostictherapeutic management in Spanish hospital emergency departments: the ALTAMIRA study. / Características y manejo diagnóstico-terapéutico de los pacientes con trombosis venosa superficial aislada en los servicios de urgencias hospitalarios españoles. Estudio ALTAMIRA.

OBJECTIVES: To describe the characteristics of patients with isolated lower-limb superficial vein thrombosis (SVT) treated in hospital emergency departments and to evaluate adherence to clinical practice guidelines on diagnosis (vein ultrasound imaging) and therapeutic management (start of anticoagulant therapy). MATERIAL AND METHODS: Retrospective cohort study in 18 Spanish emergency departments. We included all patients with a final emergency department diagnosis of lower-limb SVT aged 18 years or older between January 2016 and May 2017. Backward stepwise multiple logistic regression analysis was used to evaluate adherence to clinical practice guidelines on ordering vein ultrasound imaging and starting anticoagulant therapy. RESULTS: A total of 1166 patients were included. The mean patient age was 59.6 years, and 67.9% were women. About a quarter of the patients (24.4%) had a history of venous thromboembolic disease. Complications developed in 8.9% within 180 days: 4.6% experienced a recurrence and 3.6% progressed to SVT and 1.8% to deep vein thrombosis; pulmonary thromboembolism occurred in 0.9%. Hemorrhagic complications developed in 17 patients (1.5%). Sixteen patients (1.4%) died. Vein ultrasound imagine was ordered for 703 patients (60.3%). Anticoagulant agents were prescribed for 898 (77%) for a median period of 22 days. Variables associated with a decision to order anticoagulants were a history of venous thromboembolic disease (odds ratio [OR], 1.60; 95% CI, 1.12-2.30), varicose veins (OR, 1.40; 95% CI, 1.12-2.30); limb pain (OR, 1.44; 95% CI, 1.08-1.91); painful cord (OR, 1.30; 95% CI, 0.97-1.73); and availability of vein ultrasound images (OR, 1.60; 95% CI, 1.94-3.45). CONCLUSION: Adherence to clinical practice guidelines for the diagnosis and treatment of isolated lower-limb SVT is low in Spanish emergency departments. Ultrasound imaging is not ordered for 1 out of every 2 to 3 patients, and anticoagulant treatment is not started in 1 out of 4 patients. There is great room for improvement.

OBJETIVO: Describir las características de los pacientes diagnosticados de trombosis venosa superficial (TVS) aislada de miembros inferiores en servicios de urgencias hospitalarios (SUH), y evaluar la adherencia a las guías de práctica clínica en el manejo diagnóstico y terapéutico (realización de ecografía venosa e instauración de tratamiento anticoagulante). METODO: . Estudio de cohortes retrospectivo en 18 SUH españoles. Se incluyeron todos los pacientes atendidos en los SUH con diagnóstico final de TVS en miembros inferiores, con edad $ 18 años, de enero de 2016 a mayo de 2017. Para evaluar la no adherencia a las recomendaciones de las guías de práctica clínica (realización de ecografía venosa, e instauración de tratamiento anticoagulante) se ajustó un modelo de regresión logística múltiple por pasos hacia atrás. RESULTADOS: . Mil ciento sesenta y seis pacientes fueron incluidos. La edad media fue de 59,6 años, el 67,9% eran mujeres. El 24,4% tenían antecedentes de enfermedad tromboembólica venosa (ETV). El 8,9% tuvieron alguna complicación a 180 días [4,6% recurrencia y 3,6% progresión de TVS, 1,8% trombosis venosa profunda (TVP) y 0,9% tromboembolia pulmonar (TEP)]. Hubo 17 pacientes (1,5%) con hemorragia y 16 (1,4%) muertes. Se realizó ecografía venosa a 703 (60,3%) pacientes. Recibieron tratamiento anticoagulante 898 (77%), con una mediana de 22 días. Las variables asociadas con la decisión de anticoagular fueron: antecedentes ETV (OR 1,60; IC 95%: 1,12-2,30), varices (OR 1,40; IC 95%: 1,12-2,30), dolor de la extremidad (OR 1,44; IC 95%: 1,08-191), presencia de cordón doloroso (OR 1,30; IC 95%: 0,97-1,73) y realización de ecografía venosa (OR 1,60; IC 95%: 1,94-3,45). CONCLUSIONES: Existe una baja adherencia a las recomendaciones de las guías de práctica clínica en el manejo diagnóstico y terapéutico de los pacientes con diagnóstico de TVS aislada de miembros inferiores en los SUH españoles: no se realiza ecografía venosa en uno de cada 2-3 pacientes, y no se instaura tratamiento anticoagulante en 1 de cada 4. Esto constituye un margen de mejora muy relevante.