Event rates and risk factors for venous thromboembolism and major bleeding in a population of hospitalized adult patients with acute medical illness receiving enoxaparin thromboprophylaxis.

BACKGROUND: We aimed to describe the event rates and risk-factors for symptomatic venous thromboembolism (VTE) and major bleeding in a population of hospitalized acutely ill medical patients. METHODS: Patients ≥40 years old and hospitalized for acute medical illness who initiated enoxaparin prophylaxis were selected from the US Optum research database. Rates of symptomatic VTE and major bleeding at 90-days were estimated via the Kaplan-Meier (KM) method. Risk factors were identified via the Cox proportional hazards model. RESULTS: A total of 123,022 patients met the selection criteria. The KM rates of VTE and major bleeding at 90-days were 3.5 % and 2.2 %, respectively. Among subgroups, the risk of VTE varied from 3.0 % in patients with ischemic stroke to 6.9 % in patients with a cancer-related hospitalization, and the risk of major bleeding varied from 1.9 % in patients with inflammatory conditions to 3.6 % in patients with ischemic stroke. Key risk factors for VTE were prior VTE (HR=4.15, 95 % confidence interval [CI] 3.80-4.53), cancer-related hospitalization (HR=2.35, 95 % CI 2.10-2.64), and thrombophilia (HR=1.64, 95 % CI 1.29-2.08). Key risk factors for major bleeding were history of major bleeding (HR=2.17, 95 % CI 1.72-2.74), history of non-major bleeding (HR=2.46, 95 % CI 2.24-2.70), and hospitalization for ischemic stroke (2.42, 95 % CI 2.11-2.78). CONCLUSION: There is substantial heterogeneity in the event rates for VTE and major bleeding in acute medically ill patients. History of VTE and cancer related hospitalization represent profiles with a high risk of VTE, where continued VTE prophylaxis may be warranted.

Enoxaparin for symptomatic COVID-19 managed in the ambulatory setting: An individual patient level analysis of the OVID and ETHIC trials.

BACKGROUND: Antithrombotic treatment may improve the disease course in non-critically ill, symptomatic COVID-19 outpatients. METHODS: We performed an individual patient-level analysis of the OVID and ETHIC randomized controlled trials, which compared enoxaparin thromboprophylaxis for either 14 (OVID) or 21 days (ETHIC) vs. no thromboprophylaxis for outpatients with symptomatic COVID-19 and at least one additional risk factor. The primary efficacy outcome included all-cause hospitalization and all-cause death within 30 days from randomization. Both studies were prematurely stopped for futility. Secondary efficacy outcomes were major symptomatic venous thromboembolic events, arterial cardiovascular events, or their composite occurring within 30 days from randomization. The same outcomes were assessed over a 90-day follow-up. The primary safety outcome was major bleeding (ISTH criteria). RESULTS: A total of 691 patients were randomized: 339 to receive enoxaparin and 352 to the control group. Over 30-day follow-up, the primary efficacy outcome occurred in 6.0 % of patients in the enoxaparin group vs. 5.8 % of controls for a risk ratio (RR) of 1.05 (95%CI 0.57-1.92). The incidence of major symptomatic venous thromboembolic events and arterial cardiovascular events was 0.9 % vs. 1.8 %, respectively (RR 0.52; 95%CI 0.13-2.06). Most cardiovascular thromboembolic events were represented by symptomatic venous thromboembolic events, occurring in 0.6 % vs. 1.5 % of patients, respectively. A similar distribution of outcomes between the treatment groups was observed over 90 days. No major bleeding occurred in the enoxaparin group vs. one (0.3 %) in the control group. CONCLUSIONS: We found no evidence for the clinical benefit of early administration of enoxaparin thromboprophylaxis in outpatients with symptomatic COVID-19. These results should be interpreted taking into consideration the relatively low occurrence of events.

Challenges of extended venous thromboembolism prophylaxis in medical and surgical patients.

Patients hospitalized for acute medical and surgical illnesses are at risk of developing venous thromboembolism (VTE) during hospitalization and after discharge. Extended pharmacological prophylaxis beyond the hospital stay is recommended for patients undergoing surgeries at high risk for VTE and for selected groups of hospitalized medical patients. This practice involves several challenges, from identification of at-risk populations eligible for extended prophylaxis to choice of the most appropriate anticoagulant and definition of the ideal duration of use. This review will present the main VTE risk assessment models for hospitalized medical and surgical patients, the current recommendations for use of extended prophylaxis, and its limitations and benefits.

Thromboprophylactic low-molecular-weight heparin versus standard of care in unvaccinated, at-risk outpatients with COVID-19 (ETHIC): an open-label, multicentre, randomised, controlled, phase 3b trial.

BACKGROUND: COVID-19 is associated with inflammation and an increased risk of thromboembolic complications. Prophylactic doses of low-molecular-weight heparin have been used in hospitalised and non-critically ill patients with COVID-19. We aimed to evaluate the efficacy and safety of prophylactic low-molecular-weight heparin (enoxaparin) versus standard of care (no enoxaparin) in at-risk outpatients with COVID-19. METHODS: This open-label, multicentre, randomised, controlled, phase 3b trial (ETHIC) was done at 15 centres in six countries (Belgium, Brazil, India, South Africa, Spain, and the UK). We consecutively enrolled participants aged at least 30 years who had not received a COVID-19 vaccine and had symptomatic, confirmed COVID-19 in the outpatient setting plus at least one risk factor for severe disease. Within 9 days of symptom onset and by use of a web-based random block design (block size either 2 or 4), eligible participants were randomly assigned (1:1) to receive either subcutaneous enoxaparin for 21 days (40 mg once daily if they weighed <100 kg and 40 mg twice daily if they weighed ≥100 kg) or standard of care (without enoxaparin). The primary efficacy endpoint was the composite of all-cause hospitalisation and all-cause mortality at 21 days after randomisation and, in our main analysis, was analysed in the intention-to-treat population, which comprised all patients who were randomly assigned. Safety was also analysed in the intention-to-treat population for our main analysis. This trial is registered with ClinicalTrials.gov, NCT04492254, and is complete. FINDINGS: Following the advice of the Data and Safety Monitoring Board, this study was terminated early due to slow enrolment and a lower-than-expected event rate. Between Oct 27, 2020, and Nov 8, 2021, 230 patients with COVID-19 were assessed for eligibility, of whom 219 were enrolled and randomly assigned to receive standard of care (n=114) or enoxaparin (n=105). 96 (44%) patients were women, 122 (56%) were men, and one patient had missing sex data. 141 (65%) of 218 participants with data on race and ethnicity were White, 60 (28%) were Asian, and 16 (7%) were Black, mixed race, or Arab or Middle Eastern. Median follow-up in both groups was 21 days (IQR 21-21). There was no difference in the composite of all-cause mortality and hospitalisation at 21 days between the enoxaparin group (12 [11%] of 105 patients) and the standard-of-care group (12 [11%] of 114 patients; unadjusted hazard ratio 1·09 [95% CI 0·49-2·43]; log-rank p=0·83). At 21 days, two (2%) of 105 patients in the enoxaparin group (one minor bleed and one bleed of unknown severity) and one (1%) of 114 patients in the standard-of-care group (major abnormal uterine bleeding) had a bleeding event. 22 (21%) patients in the enoxaparin group and 13 (11%) patients in the standard-of-care group had adverse events. The most common adverse event in both groups was COVID-19-related pneumonia (six [6%] patients in the enoxaparin group and five [4%] patients in the standard-of-care group). One patient in the enoxaparin group died and their cause of death was unknown. INTERPRETATION: The ETHIC trial results suggest that prophylaxis with low-molecular-weight heparin had no benefit for at-risk outpatients with COVID-19. Although the trial was terminated early, our data, combined with data from similar studies, provide further insights to inform international guidelines and influence clinical practice. FUNDING: The Thrombosis Research Institute and Sanofi UK.

Venous thromboembolism risk, prophylaxis and management in cancer patients with COVID-19: An unmet medical need.

Cancer patients exhibit an increased risk of venous thromboembolism (VTE), with VTE being the second leading cause of morbidity and mortality in these patients. The implementation of lockdowns following the COVID-19 pandemic has resulted in decreased mobility and delayed access to care, thus further increasing the susceptibility to VTE. Cancer patients may also be at a higher risk of SARS-CoV-2 infection and have been shown to be more likely to experience severe COVID-19 disease compared to patients without cancer. Given that both cancer and COVID-19 exhibit a hypercoagulable state, stasis of blood flow, and endothelial injury, cancer patients with COVID-19 constitute a vulnerable population with a high risk of thrombosis and bleeding. However, to date there are limited studies evaluating whether cancer patients infected with SARS-CoV-2 have a higher VTE incidence than COVID-19 patients without cancer, how to assess the risk of VTE, prophylaxis and treatment in this special population. Herein, we highlight the urgent need for studies in cancer patients with COVID-19 to ensure appropriate patient care and improve clinical outcomes.

Desafios da profilaxia estendida do tromboembolismo venoso em pacientes clínicos e cirúrgicos / Challenges of extended venous thromboembolism prophylaxis in medical and surgical patients

Resumo Pacientes hospitalizados por doenças clínicas e cirúrgicas agudas estão sob risco de desenvolvimento de tromboembolismo venoso (TEV) durante a hospitalização e após a alta. A profilaxia farmacológica estendida além do período da hospitalização é recomendada para pacientes submetidos a cirurgias de alto risco de TEV e para grupos selecionados de pacientes clínicos hospitalizados. Diversos desafios envolvem essa prática, desde o reconhecimento das populações de risco elegíveis para a extensão da profilaxia até a escolha do anticoagulante mais adequado e a definição do tempo ideal de utilização. Os principais modelos de avaliação de risco de TEV em pacientes clínicos e cirúrgicos hospitalizados, as recomendações atuais para uso da profilaxia estendida e suas limitações e benefícios serão apresentados nesta revisão.

Abstract Patients hospitalized for acute medical and surgical illnesses are at risk of developing venous thromboembolism (VTE) during hospitalization and after discharge. Extended pharmacological prophylaxis beyond the hospital stay is recommended for patients undergoing surgeries at high risk for VTE and for selected groups of hospitalized medical patients. This practice involves several challenges, from identification of at-risk populations eligible for extended prophylaxis to choice of the most appropriate anticoagulant and definition of the ideal duration of use. This review will present the main VTE risk assessment models for hospitalized medical and surgical patients, the current recommendations for use of extended prophylaxis, and its limitations and benefits.

Management of Cancer-Associated Thrombosis: Unmet Needs and Future Perspectives.

Patients with cancer are at a high risk of symptomatic venous thromboembolism (VTE), which is a common cause of morbidity and mortality in this patient population. Increased risk of recurrent VTE and bleeding complications are two major challenges associated with therapeutic anticoagulation in these patients. Long-term therapy with low-molecular-weight heparins (LMWHs) has been the standard of care for the treatment of cancer-associated VTE given its favorable risk-benefit ratio in comparison with vitamin K antagonists. Direct oral anticoagulants (DOACs), which offer the convenience of oral administration and have a rapid onset of action, have recently emerged as a new treatment option for patients with cancer-associated thrombosis (CT). Randomized clinical trial data with head-to-head comparisons between DOACs and LMWHs showed that overall, DOACs have a similar efficacy profile but a higher risk of bleeding was observed in some of these studies. This review aims to identify unmet needs in the treatment of CT. We discuss important considerations for clinicians tailoring anticoagulation (1) drug-drug interactions, (2) risk of bleeding (e.g., gastrointestinal bleeding), (3) thrombocytopenia, hematological malignancies, (4) metastatic or primary brain tumors, and (5) renal impairment. Additional research is warranted in several clinical scenarios to help clinicians on the best therapeutic approach.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3­0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59­1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61­8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.

Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy

ABSTRACT Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy.

Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Alopecia in anticoagulated patients.

Alopecia is a common complication of anticoagulant therapy that may have important psychological repercussions for patients, especially female patients, and can interfere with the decision to extend anticoagulation. This review aims to describe the mechanisms potentially involved in the genesis of alopecia during anticoagulant therapy, since these are not yet fully understood, and discusses the existing therapies for the most appropriate management.

Venous thromboembolism prophylaxis protocols at Brazilian hospitals - PROTEV Brazil.

BACKGROUND: In common with other international guidelines, the Agency for Healthcare Research and Quality recommends implementation of venous thromboembolism (VTE) prophylaxis programs in hospitals as a measure for patient safety. The VTE Safety Zone Program (VTESZ) proposes a model for incorporation of systematic VTE risk-assessment into hospital routines, with continuing institutional and multidisciplinary participation. OBJECTIVES: To evaluate implementation of VTE prophylaxis initiatives in Brazilian hospitals that have adhered to the VTESZ Program. METHODS: Questionnaires were e-mailed to VTESZ Program representatives at hospitals visited up to July 2016. RESULTS: Of the 132 invitations sent, 68 answers were obtained and 50 (73.5%) were complete. 61.5% of participating hospitals had between 100 and 250 beds, and 65.4% had more than 20 intensive care beds; 61.5% reported having hospital accreditation, 86.3% had VTE prophylaxis committees, and 58% had electronic medical records. VTE risk assessments using the Brazilian guidelines or the Padua or Caprini scores were noted on the electronic medical record in 56.9% and were a mandatory step in 45.1% of the cases. VTE risk reassessment was requested prior to discharge in only 25% of hospitals and several issues were cited that negatively affect the VTESZ implementation process. CONCLUSIONS: This study provides an overview of implementation of VTESZ in Brazilian hospitals. Systematic risk assessment is not yet conducted for most patients. Recognition of various issues affecting the process may lead to new strategies for achieving adequate prophylaxis and safety of hospitalized patients.

Alopecia em pacientes anticoagulados / Alopecia in anticoagulated patients

Resumo A alopecia é uma complicação comum da terapia anticoagulante que pode ter repercussões psicológicas importantes nos pacientes, especialmente nos do sexo feminino, e interferir na decisão de extensão da anticoagulação. Esta revisão tem como objetivo descrever os mecanismos potencialmente envolvidos na gênese da alopecia durante a terapia anticoagulante, pois eles ainda não estão totalmente esclarecidos, e as terapias existentes, para a adoção das condutas mais adequadas.

Abstract Alopecia is a common complication of anticoagulant therapy that may have important psychological repercussions for patients, especially female patients, and can interfere with the decision to extend anticoagulation. This review aims to describe the mechanisms potentially involved in the genesis of alopecia during anticoagulant therapy, since these are not yet fully understood, and discusses the existing therapies for the most appropriate management.

Highlights from the IV International Symposium of Thrombosis and Anticoagulation (ISTA), October 20-21, 2011, Salvador, Bahia, Brazil.

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Fourth International Symposium of Thrombosis and Anticoagulation was held in Salvador, Bahia, Brazil, from October 20-21, 2011. 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.

[Impact of a program for venous thromboembolism prophylaxis in hospitalized patients in four hospitals in Salvador]. / Impacto de um programa para profilaxia de tromboembolismo venoso em pacientes clínicos em quatro hospitais de Salvador.

UNLABELLED: There is a discrepancy between guideline recommendations and practice of venous thromboembolism (VTE) prophylaxis in hospitals worldwide. OBJECTIVE: To implement a program using a risk-assessment tool (RAT) for VTE and educational lectures based on the Brazilian Guidelines for VTE Prophylaxis for Medical Patients and to evaluate the impact of these tools on adequacy of VTE prophylaxis in 4 hospitals in Salvador, Bahia. METHODS: We performed two cross-sectional surveys before and after the implementation of the program to compare the proportion of patients at-risk of VTE and the changes in the adequacy of VTE prophylaxis. RESULTS: We compared the data of 219 medical patients before with 292 patients after the program. The rates of patients with at least one risk factor for VTE and with contraindications (CI) for heparins were similar: 95% vs. 98% (p=0.13), and 42% vs. 34% (p=0.08), respectively. In both studies, 75% vs. 82% (p=0.06) were candidates for prophylaxis, and 44% vs. 55% (p =0.02) were candidates for prophylaxis and had no CI for heparin. After the program there was an increase in the use of mechanical prophylaxis 0.9% vs. 4.5% (p=0.03) and a decrease in pharmacological prophylaxis, 55.3% vs. 47.9% (p=0.04). However, there was a significant increase of use of the recommended doses of heparins, 53% vs. 75 (p<0.001). CONCLUSION: There is underutilization of VTE prophylaxis in Brazilian hospitals. Strategies based on passive distribution of RAT and educational lectures were not sufficient to improve the practice of prophylaxis, but improved the adequacy of VTE prophylaxis in hospitalized patients.

Recomendações para o manejo da tromboembolia pulmonar, 2010 / Recommendations for the management of pulmonary thromboembolism, 2010

A tromboembolia pulmonar constitui, juntamente com a trombose venosa profunda, a condição denominada tromboembolismo venoso. Apesar dos avanços, a morbidade e a mortalidade atribuídas a essa doença ainda são elevadas, pois os pacientes apresentam doenças mais complexas, são submetidos a um maior número de procedimentos invasivos e sobrevivem por mais tempo. Embora existam inúmeras diretrizes internacionais disponíveis, optou-se por redigir estas recomendações para sua aplicação na prática médica nacional, embasadas nas melhores evidências na literatura e na opinião do grupo de consultores. Este documento é apenas uma ferramenta para o atendimento dos pacientes, e, embora possa ser aplicado na maioria das situações, o médico deve adaptar as informações a sua realidade local e ao caso específico. O diagnóstico de tromboembolia pulmonar é realizado através da combinação da probabilidade clínica pré-teste (escores) com o resultado dos exames de imagem, sendo atualmente o método de eleição a angiotomografia computadorizada. É fundamental a estratificação do risco de desfecho desfavorável, sendo a instabilidade hemodinâmica o preditor mais importante. Pacientes de baixo risco devem ser tratados com heparina, comumente as de baixo peso molecular. Pacientes de alto risco requerem vigilância intensiva e uso de trombolíticos em alguns casos. A longo prazo, os pacientes devem receber anticoagulantes por no mínimo três meses, sendo sua manutenção decidida pela presença de fatores de risco para a recorrência e a probabilidade de sangramento. A profilaxia é altamente eficaz e deve ser amplamente utilizada, tanto em pacientes clínicos como cirúrgicos, conforme os grupos de risco. Finalmente, são feitas recomendações relacionadas ao diagnóstico, tratamento e prevenção da tromboembolia pulmonar.

Pulmonary thromboembolism and deep vein thrombosis together constitute a condition designated venous thromboembolism. Despite the advances, the morbidity and the mortality attributed to this condition are still high, because the patients present with more complex diseases, are submitted to a greater number of invasive procedures and survive longer. Although there are various international guidelines available, we decided to write these recommendations for their application in medical practice in Brazil. These recommendations are based on the best evidence in the literature and the opinion of the advisory committee. This document is only a tool for use in the management of patients. Although the recommendations it contains can be applied to most situations, physicians should adapt its content depending on their local context and on a case-by-case basis. Pulmonary thromboembolism is diagnosed by evaluating pre-test clinical probability (scores) together with the results of imaging studies, the current method of choice being CT angiography. Stratification of the risk for an unfavorable outcome is fundamental. Hemodynamic instability is the most important predictor. Low-risk patients should be treated with heparin, commonly low-molecular-weight heparins. High-risk patients require intensive monitoring and, in some cases, thrombolytic therapy. In the long term, patients should receive anticoagulants for at least three months. The decision to prolong this treatment is made based on the presence of risk factors for the recurrence of the condition and the probability of bleeding. Prophylaxis is highly effective and should be widely used in clinical and surgical patients alike, according to their risk group. Finally, we include recommendations regarding the prevention, diagnosis and treatment of pulmonary thromboembolism.

Impacto de um programa para profilaxia de tromboembolismo venoso em pacientes clínicos em quatro hospitais de Salvador / Impact of a program for venous thromboembolism prophylaxis in hospitalized patients in four hospitals in Salvador

OBJETIVO: Implementar um programa hospitalar de profilaxia de TEV através da criação de uma comissão, da realização de palestras e da distribuição de algoritmos baseados na Diretriz Brasileira para Profilaxia de TEV em Pacientes Clínicos e avaliar seu impacto na adequação da utilização de profilaxia em quatro hospitais de Salvador, Bahia. MÉTODOS: Foram realizados dois estudos de corte-transversal, um antes e um depois da implementação do programa, e comparadas as proporções de pacientes em risco de TEV e as mudanças na adequação da profilaxia. RESULTADOS: Foram avaliados 219 pacientes clínicos antes e 292 depois do programa. As taxas daqueles com pelo menos um fator de risco para TEV e daqueles com contra indicação (CI) para heparina foram semelhantes nos dois grupos: 95 por cento vs. 98 por cento (p=0,13) e 42 por cento vs. 34 por cento (p=0,08), respectivamente. Nos dois estudos, 75 por cento vs. 82 por cento (p=0,06) eram candidates para profilaxia, e 44 por cento vs. 55 por cento (p =0,02) eram candidatos sem qualquer CI para heparina. Após o programa, utilizou-se mais profilaxia mecânica, 0,9 por cento vs. 4,5 por cento (p=0,03) e menos profilaxia farmacológica, 55,3 por cento vs. 47,9 por cento (p=0,04), embora tenha havido um aumento significativo na utilização das doses corretas das heparinas, 53 por cento vs. 75 por cento (p<0,001). CONCLUSÃO: A profilaxia de TEV é subutilizada nos hospitais brasileiros. Aulas de educação continuada e distribuição passiva de algoritmos de profilaxia de TEV são insuficientes para melhorar a utilização, mas melhoram a adequação da profilaxia.

SUMMARY: There is a discrepancy between guideline recommendations and practice of venous thromboembolism (VTE) prophylaxis in hospitals worldwide. OBJECTIVE: To implement a program using a risk-assessment tool (RAT) for VTE and educational lectures based on the Brazilian Guidelines for VTE Prophylaxis for Medical Patients and to evaluate the impact of these tools on adequacy of VTE prophylaxis in 4 hospitals in Salvador, Bahia. METHODS: We performed two cross-sectional surveys before and after the implementation of the program to compare the proportion of patients at-risk of VTE and the changes in the adequacy of VTE prophylaxis. RESULTS: We compared the data of 219 medical patients before with 292 patients after the program. The rates of patients with at least one risk factor for VTE and with contraindications (CI) for heparins were similar: 95 percent vs. 98 percent (p=0.13), and 42 percent vs. 34 percent (p=0.08), respectively. In both studies, 75 percent vs. 82 percent (p=0.06) were candidates for prophylaxis, and 44 percent vs. 55 percent (p =0.02) were candidates for prophylaxis and had no CI for heparin. After the program there was an increase in the use of mechanical prophylaxis 0.9 percent vs. 4.5 percent (p=0.03) and a decrease in pharmacological prophylaxis, 55.3 percent vs. 47.9 percent (p=0.04). However, there was a significant increase of use of the recommended doses of heparins, 53 percent vs. 75 (p<0.001). CONCLUSION: There is underutilization of VTE prophylaxis in Brazilian hospitals. Strategies based on passive distribution of RAT and educational lectures were not sufficient to improve the practice of prophylaxis, but improved the adequacy of VTE prophylaxis in hospitalized patients.

Inadequação de tromboprofilaxia venosa em pacientes clínicos hospitalizados / Inadequacy of thromboprophylaxis in hospitalized medical patients

O risco de tromboembolismo venoso (TEV) é alto em pacientes internados, mas pode ser reduzido com a utilização adequada de profilaxia. OBJETIVO: Avaliar a utilização e adequação de profilaxia para TEV em pacientes clínicos internados. MÉTODOS: Estudo de coorte transversal em pacientes internados por doenças clínicas em quatro hospitais de Salvador. RESULTADOS: Foram avaliados 226 pacientes: 15,5 por cento em UTIs clínicas, 79 por cento tinham idade > 40 anos e 48 por cento eram homens. A maioria (97 por cento) apresentava pelo menos um fator de risco (FR) para TEV: mobilidade reduzida em 79 por cento e diagnóstico principal como FR em 62 por cento. Dos 208 candidatos a profilaxia, 54 por cento receberam alguma forma: heparina não fracionada (HNF) em 44 por cento, heparina de baixo peso molecular (HBPM) em 56 por cento e métodos mecânicos em dois pacientes. A taxa de utilização foi semelhante entre hospitais privados e públicos (51 por cento versus 49 por cento), mas HBPM predominou em privados (97 por cento) e sem residência médica e HNF em públicos (86 por cento). HBPM foi usada mais freqüentemente que HNF em pacientes > 40 anos, em brancos que em negros ou mulatos, e menos freqüentemente em pacientes com contra-indicações para heparina. Dos 112 pacientes com profilaxia, 63 por cento receberam dosagem adequada: HBPM em 95,2 por cento e HNF em 20,4 por cento. Profilaxia para TEV foi adequada em apenas 33,6 por cento (70/208) dos pacientes. CONCLUSÃO: FR para TEV são freqüentes em pacientes clínicos. Existe ampla variabilidade da profilaxia prescrita em hospitais públicos e privados. HBPM é utilizada mais adequadamente que HNF, entretanto, apenas a minoria dos pacientes clínicos hospitalizados e candidatos a profilaxia recebem dosagem adequada.

BACKGROUND: The risk of venous thromboembolism (VTE) is high in hospitalized patients, however it can be reduced by adequate prophylaxis. OBJECTIVE: To evaluate the adequacy of VTE prophylaxis in hospitalized medical patients. METHODS: A cross-sectional study was performed in hospitalized patients with acute medical illnesses in 4 hospitals of Salvador. RESULTS: We evaluated 226 consecutive patients: 15.5 percent in medical ICU, 79 percent > 40 years of age and 48 percent male. The majority (97 percent) had a least 1 risk factor (RF) for VTE, 79 percent had reduced mobility and 62 percent were diagnosed as having a RF at admission. Of the 208 prophylaxis candidates, 54 percent received some form of prophylaxis: unfractionated heparin (UFH) in 44 percent, low molecular weight heparin (LMWH) in 56 percent and mechanical methods in 2 patients. The utilization rate was similar in private and public hospitals. (51 percent vs. 49 percent), but LMWH was more common in private hospitals, without a residence program (97 percent), and UFH in the public ones (86 percent). LMWH was more frequently used than UFH in patients > 40 years of age, more often in Caucasian than in Black patients, and less frequently in those with contraindications for heparin. Of the 112 patients receiving prophylaxis, 63 percent received adequate dosages: LMWH in 95.2 percent and UFH in 20.4 percent. VTE prophylaxis was adequate in only 33.6 percent (70/208) of the patients. CONCLUSION: Risk Factors for VTE were frequent in medical patients. There was considerable variability of the VTE prophylaxis prescribed in private and public hospitals. LMWH was used more appropriately than UFH. However, only a minority of patients candidates for prophylaxis, received adequate dosages.

[Inadequacy of thromboprophylaxis in hospitalized medical patients]. / Inadequação de tromboprofilaxia venosa em pacientes clínicos hospitalizados.

BACKGROUND: The risk of venous thromboembolism (VTE) is high in hospitalized patients, however it can be reduced by adequate prophylaxis. OBJECTIVE: To evaluate the adequacy of VTE prophylaxis in hospitalized medical patients. METHODS: A cross-sectional study was performed in hospitalized patients with acute medical illnesses in 4 hospitals of Salvador. RESULTS: We evaluated 226 consecutive patients: 15.5% in medical ICU, 79% > 40 years of age and 48% male. The majority (97%) had a least 1 risk factor (RF) for VTE, 79% had reduced mobility and 62% were diagnosed as having a RF at admission. Of the 208 prophylaxis candidates, 54% received some form of prophylaxis: unfractionated heparin (UFH) in 44%, low molecular weight heparin (LMWH) in 56% and mechanical methods in 2 patients. The utilization rate was similar in private and public hospitals. (51% vs. 49%), but LMWH was more common in private hospitals, without a residence program (97%), and UFH in the public ones (86%). LMWH was more frequently used than UFH in patients > 40 years of age, more often in Caucasian than in Black patients, and less frequently in those with contraindications for heparin. Of the 112 patients receiving prophylaxis, 63% received adequate dosages: LMWH in 95.2% and UFH in 20.4%. VTE prophylaxis was adequate in only 33.6% (70/208) of the patients. CONCLUSION: Risk Factors for VTE were frequent in medical patients. There was considerable variability of the VTE prophylaxis prescribed in private and public hospitals. LMWH was used more appropriately than UFH. However, only a minority of patients candidates for prophylaxis, received adequate dosages.