Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia-a prospective, single-center, analytical, cross-sectional study.

Background: Patients with hematological malignancies (HM) frequently present thrombocytopenia and higher risk of bleeding. Although transfusion is associated with higher risk of adverse events and poor outcomes, prophylactic transfusion of platelets is a common practice to prevent hemorrhagic complications. Thromboelastometry has been considered a better predictor for bleeding than isolated platelet counts in different settings. In early stages of sepsis, hypercoagulability may occur due to higher fibrinogen levels. Objectives: To evaluate the behavior of coagulation in patients with HM who develop sepsis and to verify whether a higher concentration of fibrinogen is associated with a proportional increase in maximum clot firmness (MCF) even in the presence of severe thrombocytopenia. Methods: We performed a unicentric analytical cross-sectional study with 60 adult patients with HM and severe thrombocytopenia, of whom 30 had sepsis (sepsis group) and 30 had no infections (control group). Coagulation conventional tests and specific coagulation tests, including thromboelastometry, were performed. The main outcome evaluated was MCF. Results: Higher levels of fibrinogen and MCF were found in sepsis group. Both fibrinogen and platelets contributed to MCF. The relative contribution of fibrin was significantly higher (60.5 ± 12.8% vs 43.6 ± 9.7%; P < .001) and that of platelets was significantly lower (39.5 ± 12.8% vs 56.4 ± 9.7%; P < .001) in the sepsis group compared with the control group. Conclusion: Patients with sepsis and HM presented higher concentrations of fibrinogen than uninfected patients, resulting in greater MCF amplitudes even in the presence of thrombocytopenia.

Epidemiology of the use of inferior vena cava filters in Brazil between 2008 and 2019.

OBJECTIVES: The primary objective was to study the totality of inferior vena cava filter placements and their temporal and geographic distribution in the Brazilian Public Health System, which insures more than 160 million Brazilians. The secondary objective was to analyze in-hospital mortality after filter placement and deaths due to pulmonary embolism. METHODS: Public and open data on in-hospital mortality due to pulmonary embolism and on rates of inferior vena cava filters placement, its associated diagnosis, and in-hospital mortality in Brazilian public hospitals between January 2008 and December 2019 were extracted from Ministry of Health databases. RESULTS: A total of 9108 inferior vena cava filters were placed, 98.18% of which was therapeutic. We observed a significant increase in the use of these devices over the years, from 508 inferior vena cava filters placed in 2008 to 965 in 2019. In-hospital mortality rate in patients who received inferior vena cava filters was 6.21%, stable over time, and 96.64% of causes of these causes were attributed to venous thromboembolism. The in-hospital mortality rate due to pulmonary embolism, regardless of the placement of vena cava filters, has increased significantly. CONCLUSION: We observed a low but increasing rate of inferior vena cava filter placements in Brazil between 2008 and 2019, most indications were therapeutic. Our findings were heterogeneous across Brazilian regions and contrasted to those observed in the USA, which is likely due to cultural and socioeconomic factors.

Rivaroxaban Versus Enoxaparin for Thromboprophylaxis After major Gynecological Cancer Surgery: The VALERIA Trial : Venous thromboembolism prophylAxis after gynecoLogical pElvic cancer surgery with RIvaroxaban versus enoxAparin (VALERIA trial).

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) prevention after major gynecological cancer surgery might be an alternative to parenteral low-molecular-weight heparin (LMWH). Patients undergoing major gynecological cancer surgery were randomized at hospital discharge to receive rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily for 30 days. The primary efficacy outcome was a combination of symptomatic VTE and VTE-related death or asymptomatic VTE at day 30. The primary safety outcome was the incidence of major or clinically relevant nonmajor bleeding. Two hundred and twenty-eight patients were enrolled and randomly assigned to receive rivaroxaban (n = 114)or enoxaparin (n = 114). The trial was stopped due to a lower-than-expected event rate. The primary efficacy outcome occurred in 3.51% of patients assigned to rivaroxaban and in 4.39% of patients assigned to enoxaparin (relative risk 0.80, 95% CI 0.22 to 2.90; p = 0.7344). Patients assigned to rivaroxaban had no primary bleeding event, and 3 patients (2.63%) in the enoxaparin group had a major or CRNM bleeding event (hazard ratio, 0.14; 95% CI, 0.007 to 2.73; P = 0.1963). In patients undergoing major gynecological cancer surgery, thromboprophylaxis with rivaroxaban 10 mg daily for 30 days had similar rates of thrombotic and bleeding events compared to parenteral enoxaparin 40 mg daily. While the power is limited due to not reaching the intended sample size, our results support the hypothesis that DOACs might be an attractive alternative strategy to LMWH to prevent VTE in this high-risk population.

Chronic diseases, chest computed tomography, and laboratory tests as predictors of severe respiratory failure and death in elderly Brazilian patients hospitalized with COVID-19: a prospective cohort study.

BACKGROUND: The primary risk factors for severe respiratory failure and death in the elderly hospitalized with COVID-19 remain unclear. OBJECTIVE: To determine the association of chronic diseases, chest computed tomography (CT), and laboratory tests with severe respiratory failure and mortality in older adults hospitalized with COVID-19. METHOD: This was a prospective cohort with 201 hospitalized older adults with COVID-19. Chronic diseases, chest CT, laboratory tests, and other data were collected within the first 48 h of hospitalization. Outcomes were progression to severe respiratory failure with the need of mechanical ventilation (SRF/MV) and death. RESULTS: The mean age was 72.7 ± 9.2 years, and 63.2% were men. SRF/MV occurred in 16.9% (p < 0.001), and death occurred in 8%. In the adjusted regression analyses, lung involvement over 50% [odds ratio (OR): 3.09 (1.03-9.28; 0.043)], C-reactive protein (CRP) > 80 ng/mL [OR: 2.97 (0.99-8.93; 0.052)], Vitamin D < 40 ng/mL [OR: 6.41 (1.21-33.88; 0.029)], and hemoglobin < 12 g/mL [OR: 3.32 (1.20-9.20; 0.020)] were independent predictors for SFR/MV, while chronic atrial fibrillation [OR: 26.72 (3.87-184.11; 0.001)], cancer history [OR:8.32 (1.28-53.91; 0.026)] and IL-6 > 40 pg/mL [OR:10.01 (1.66-60.13; 0.012)] were independent predictors of death. CONCLUSION: In hospitalized older adults with COVID-19, tomographic pulmonary involvement > 50%, anemia, vitamin D below 40 ng/mL, and CRP above 80 mg/L were independent risk factors for progression to SRF/MV. The presence of chronic atrial fibrillation, previous cancer, IL-6 > 40 pg/mL, and anemia were independent predictors of death.

Consenso Colombiano para la prevención, diagnóstico y manejo de condiciones trombóticas en pacientes adultos con COVID-19: aplicando el Marco de la Evidencia a la Decisión (EtD) GRADE / Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adult patients with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

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Abstract Recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. In this context, the aim was to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: A rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: Recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.

Guidelines for prophylaxis and anti-thrombotic treatment for patients with COVID-19. Consensus of the Latin American Cooperative Group on Hemostasis and Thrombosis (CLAHT) / Guía de profilaxia y tratamiento antitrombótico para pacientes con COVID-19. Consenso del Grupo Cooperativo Latinoamericano en Hemostasia y Trombosis (CLAHT)

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.

La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.

Coagulation profile of COVID-19 patients admitted to the ICU: An exploratory study.

BACKGROUND: Coagulation abnormalities in COVID-19 patients have not been addressed in depth. OBJECTIVE: To perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19. METHODS: Conventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10. RESULTS: Thirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM-FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ​​than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability. CONCLUSION: COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system.

Consenso colombiano para la prevención, el diagnóstico y el tratamiento de condiciones trombóticas en adultos con COVID-19: aplicando el Marco de la Evidencia a la Decisión (EtD) GRADE / Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adults with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

Introducción estudios recientes han reportado fenómenos trombóticos o coagulopatía en pacientes con COVID-19. Hay posiciones divergentes en cuanto a la prevención, el diagnóstico y el tratamiento de estos fenómenos, y la práctica clínica actual está basada únicamente en deducciones por extensión a partir de estudios retrospectivos, series de casos, estudios observacionales y guías internacionales desarrolladas previas a la pandemia. Objetivo establecer una serie de recomendaciones sobre prevención, diagnóstico y manejo de las complicaciones trombóticas asociadas a COVID-19. Métodos se desarrolló una guía rápida en la que se aplicó el marco de la evidencia a la decisión (EtD) de GRADE y un sistema de participación iterativo, con análisis estadísticos y cualitativos de sus resultados. Resultados se generaron 31 recomendaciones clínicas enfocadas a: a) Pruebas de coagulación en adultos sintomáticos con sospecha de infección o infección confirmada por SARS-CoV-2; b) Tromboprofilaxis en personas adultas con diagnóstico de COVID-19 (escalas de riesgo, tromboprofilaxis de manejo ambulatorio, intrahospitalario y duración de tromboprofilaxis después del egreso de hospitalización), c) Diagnóstico y tratamiento de las complicaciones trombóticas y d) Manejo de personas con indicación previa a usar agentes anticoagulantes. Conclusiones las recomendaciones clínicas de este consenso orientan la toma de decisiones clínicas respecto a prevención, diagnóstico y tratamiento de fenómenos trombóticos en pacientes con COVID-19, y representan un acuerdo que ayudará a disminuir la dispersión en las prácticas clínicas acorde con el desafío que impone la pandemia.

Abstract Introduction: recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. Objective: to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: a rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.

Comparison of different laboratory tests in the evaluation of hemorrhagic risk of patients using rivaroxaban in the critical care setting: diagnostic accuracy study.

BACKGROUND: Rivaroxaban is a direct oral anticoagulant designed to dispense with the necessity of laboratory monitoring. However, monitoring rivaroxaban levels is necessary in certain clinical conditions, especially in the critical care setting. METHODS: This is a diagnostic accuracy study evaluating sensitivity and specificity of prothrombin time (PT), activated partial thromboplastin time (aPTT), and Dilute Russell viper venom time (dRVVT), to evaluate the hemorrhagic risk in patients taking rivaroxaban. The study used a convenience sample of 40 clinically stable patients using rivaroxaban to treat deep vein thrombosis or atrial fibrillation admitted in a private hospital in Brazil, compared to a group of 60 healthy controls. The samples from patients were collected two hours after the use of the medication (peak) and two hours before the next dose (trough). RESULTS: The correlation with the plasmatic concentration measured by anti-FXa assay was higher for PT and dRVVTS. The PT and aPTT tests presented higher specificity, while dRVVT was 100% sensible. CONCLUSIONS: There was a strong correlation between the tests and the plasma concentration of the drug. Additionally, our results demonstrated the potential use of dRVVT as a screening test in the emergency room and the need of a second test to improve specificity.

Rediscussing Anticoagulation in Distal Deep Venous Thrombosis.

BACKGROUND: Distal deep venous thrombosis (DVT) accounts for approximately half of all the cases of lower limb thrombosis. The impact and management of this condition is still controversial. This study aims to evaluate the incidence of pulmonary embolism (PE) in patients with distal DVT in comparison to proximal DVT and evaluate the correlation between DVT and PE extension. METHODS: 100 patients with acute lower limb DVT diagnosed with whole leg Doppler ultrasound from January 2006 to December 2014 were retrospectively analyzed. Active investigation for PE was carried out in all patients using multislice computed tomography angiography. Classification of DVT and PE was based on the proximal extension of the thrombus. RESULTS: The overall incidence of PE in our sample patients was 72%. In the subgroup analysis, incidence of PE was equal in both the proximal and distal DVT groups (77%, p > 0.99). PE was detected in 43% of the patients with isolated calf vein thrombosis (ICVT). No statistical difference was observed between the distribution of lobar, segmental and subsegmental PE in the 3 DVT subgroups (p = 0.665); however, truncular PE was only observed in the proximal DVT group. CONCLUSION: Distal DVT is associated with a high incidence of PE compared to proximal DVT. Distal DVT and ICVT can provoke PE with involvement of proximal vessels in the pulmonary arterial tree, even in asymptomatic patients. Our study arises discussion in the controversial debate regarding the need for routine anticoagulation in distal DVT.

Highlights from the fifth international symposium of thrombosis and anticoagulation (ISTA V), October 18-19, 2012, Belo Horizonte, Minas Gerais, Brazil.

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Fifth International Symposium of Thrombosis and Anticoagulation was held in Belo Horizonte, Minas Gerais, Brazil, on October 18-19, 2012. This scientific program was developed by clinicians for clinicians and was promoted by three major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, and Hospital do Coração Research Institute. Comprising 2 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Risk of asymptomatic pulmonary embolism in patients with deep venous thrombosis.

OBJECTIVE: The aim of our study is to evaluate the incidence of asymptomatic pulmonary embolism (PE) in patients with deep venous thrombosis (DVT), submitted to routine angiography of pulmonary vessels, and analyze the relationship between the site of DVT and extent of PE. METHODS: Between January 2006 and April 2012, 52 consecutive patients with acute inferior limb DVT were divided into two study groups composed of individuals with proximal and distal thrombotic involvement. All patients had no respiratory symptoms and were submitted to routine pulmonary computed tomography angiography for active investigation of PE. We assessed the incidence and extent of PE in both study groups. RESULTS: Thirty-eight patients (72%) had PE, detected by computed tomography angiography. The incidence of PE in patients with proximal and distal thrombosis, respectively, was 72.7% and 73.7%. Occurrence of segmental embolism was equally high in both groups, affecting 71.4% of the patients with distal thrombosis and 66.6% of the individuals with proximal DVT (P > .99). CONCLUSIONS: The incidence of asymptomatic PE observed in patients with DVT is higher than what is reported in the current literature. This supports the importance of screening and the need for high levels of suspicion regarding this complication.