Prophylaxis of venous thromboembolism in hospitalized patients admitted from Spanish emergency departments: the PROTESU II study. / Profilaxis de la enfermedad tromboembólica venosa en pacientes hospitalizados por patología médica desde los servicios de urgencias españoles: estudio PROTESU II.

OBJECTIVE: To estimate the prevalence of inappropriate use of prophylaxis to prevent venous thromboembolism (VTE) in patients with medical diseases admitted to hospital from the emergency department. To explore variables associated with inappropriate thromboprophylaxis. METHODS: Prospective multicenter cohort study in 15 hospital emergency departments. We included patients admitted for a medical condition during 7 days in the first quarter of 2022. We assessed risk for VTE with the Padua Prediction Score (PPS). Inappropriate thromboprophylaxis was defined by failure to prescribe prophylaxis in patients with a high-risk PPS assessment unless there were absolute contraindications (active bleeding or severe thrombopenia) or, alternatively, the prescription of prophylaxis in patients with a low-risk PPS assessment or absolute contraindications. A logistic regression model was adjusted for risk level to identify variables associated with inappropriate use of thromboprophylaxis. RESULTS: Of a total of 630 patients included, 450 (71.4%) had PPS scores indicating high risk for VTE; 180 patients were at low risk. Thromboprophylaxis was inappropriate in 248 patients (39.4%): 165 high-risk patients who received no prophylaxis, 82 low-risk patients who were nonetheless treated, and 1 patient who was treated in spite of severe thrombopenia. Odds ratios (ORs) revealed that the variables associated with inappropriate use of thromboprophylaxis were trauma or recent surgery (OR, 5.53; 95% CI, 1.58-19.34), presence of factors indicating risk for bleeding (OR, 2.61; 95% CI, 1.44-4.73), and hospital admission for either urinary tract infection (OR, 2.29; 95% CI, 1.07-4.87) or gastrointestinal disease (OR, 4.30; 95% CI, 1.71-10.85). CONCLUSIONS: The inappropriate use of thromboprophylaxis in Spanish emergency departments is high and associated with certain clinical characteristics.

OBJETIVO: Evaluar la inadecuación de la tromboprofilaxis farmacológica, según la escala Padua (PPS), para prevenir la enfermedad tromboembólica venosa (ETV) entre los pacientes que ingresan desde el servicio de urgencias hospitalario (SUH) por patología médica, así como las variables asociadas a su uso inadecuado. METODO: Estudio de cohortes, prospectivo, multicéntrico donde participaron 15 SUH. Se incluyeron los pacientes atendidos que requirieron ingreso por enfermedad médica durante 7 días del primer trimestre de 2022. La inadecuación de la tromboprofilaxis farmacológica se definió como la no utilización en pacientes clasificados por PPS de alto riesgo sin contraindicaciones absolutas para su uso (hemorragia activa o trombopenia grave) o su utilización en pacientes de riesgo bajo o con contraindicaciones absolutas. Se ajustó, para cada grupo de riesgo, un modelo de regresión logística para identificar las variables asociadas a la inadecuación. RESULTADOS: Se incluyeron 630 pacientes, 450 (71,4%) tenían riesgo alto y 180 (28,6%) riesgo bajo para ETV según la PPS. De ellos, la tromboprofilaxis fue inadecuada en 248 pacientes (39,4%) (165 tenían riesgo alto pero no recibieron tromboprofilaxis, 1 la recibió teniendo trombopenia grave y 82 tenían riesgo bajo pero recibieron tromboprofilaxis). Las variables asociadas con la inadecuación en pacientes de alto riesgo fueron trauma o cirugía recientes con odds ratio (OR) de OR 5,53 (IC 95%: 1,58-19,34), presencia de factores de riesgo hemorrágico con OR de 2,61 (IC 95%: 1,44-4,73), e infección del tracto urinario con OR de 2,29 (IC 95%: 1,07-4,87) y enfermedad gastrointestinal con OR de 4,30 (IC 95%: 1,71-10,85) como motivos de ingreso. CONCLUSIONES: En los SUH españoles, el uso inadecuado de la tromboprofilaxis farmacológica es elevado. Algunas características clínicas se asocian al uso inadecuado de dicha tromboprofilaxis.

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.

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.

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.

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.

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.

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.

Management and outcomes of cancer patients with venous thromboembolism presenting with thrombocytopenia.

INTRODUCTION: Treatment of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is challenging due to perceived higher risk of bleeding. MATERIAL AND METHODS: We used the RIETE registry to compare the 10- and 30-day outcomes in cancer patients with acute VTE, according to platelet count at baseline. RESULTS: As of December 2018, 15,337 cancer patients with VTE were included: 166 (1.1%) had <50 × 109 platelets/L (severe thrombocytopenia), 711 (4.6%) had 50-99 × 109/L (mild thrombocytopenia) and 14,460 (94.3%) had ≥100 × 109/L (normal count). Most patients in all subgroups received initial therapy with low-molecular-weight heparin (LMWH), but 62% of those with severe thrombocytopenia received <150 IU/kg/day LMWH, 42% received <100 IU/kg/day. The mortality rate progressively decreased with increasing platelet counts (12%, 9.4% and 3.3% respectively at 10 days, 27%, 18% and 9.4% at 30 days), but the major bleeding rates did not (1.2%, 2.5% and 1.3% respectively at 10 days, 2.4%, 4.4% and 2.2% at 30 days). On multivariable analysis, patients with severe thrombocytopenia had a similar risk for major bleeding at 10 days (OR 0.84; 95%CI 0.20-3.49) and at 30 days (OR 0.90; 95%CI 0.32-2.49), but those with mild thrombocytopenia were at increased risk both at 10 days (OR 2.11; 95%CI 1.27-3.49) and at 30 days (OR 1.91; 95%CI 1.29-2.84). CONCLUSIONS: Cancer patients with acute VTE and baseline thrombocytopenia often receive initial lower-than recommended doses of LMWH. Although caution is required, this practice seems to be safe in patients with severe thrombocytopenia. Nonetheless, there was an inverse correlation between baseline platelet count and mortality.

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.

[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.

Síndrome de Klinefelter diagnosticado en un adulto a raíz del estudio de infección respiratoria recurrente y masa mediastínica: caso clínico / Thymoma in a patient with klinefelter syndrome: case report

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.

Clinical Characteristics and Outcomes of Patients with Lung Cancer and Venous Thromboembolism.

Background The natural history of patients with lung cancer and venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics, time course, and outcomes during anticoagulation of lung cancer patients with acute, symptomatic VTE. Results As of May 2017, a total of 1,725 patients were recruited: 1,208 (70%) presented with pulmonary embolism (PE) and 517 with deep vein thrombosis (DVT). Overall, 865 patients (50%) were diagnosed with cancer <3 months before, 1,270 (74%) had metastases, and 1,250 (72%) had no additional risk factors for VTE. During anticoagulation (median, 93 days), 166 patients had symptomatic VTE recurrences (recurrent DVT: 86, PE: 80), 63 had major bleeding (intracranial 11), and 870 died. The recurrence rate was twofold higher than the major bleeding rate during the first month, and over threefold higher beyond the first month. Fifty-seven patients died of PE and 15 died of bleeding. Most fatal PEs (84%) and most fatal bleeds (67%) occurred within the first month of therapy. Nine patients with fatal PE (16%) died within the first 24 hours. Of 72 patients dying of PE or bleeding, 15 (21%) had no metastases and 29 (40%) had the VTE shortly after surgery or immobility. Conclusion Active surveillance on early signs and/or symptoms of VTE in patients with recently diagnosed lung cancer and prescription of prophylaxis in those undergoing surgery or during periods of immobilization might likely help prevent VTE better, detect it earlier, and treat it more efficiently.