Incidence, diagnosis, treatment methods, and outcomes of clinically suspected venous thromboembolic disease in patients with COVID-19 in a quaternary hospital in Brazil.

BACKGROUND: Prothrombotic states have been associated with viral infections and the novel Sars-COV-2 infection has been associated with elevated D-dimer levels, although no causal relation has been clearly established. OBJECTIVES: This study presents an epidemiological analysis of manifest VTE episodes in a group of patients hospitalized because of COVID-19. METHODS: Medical records of patients who presented symptomatic deep vein thrombosis and/or pulmonary embolism in concomitance with confirmed COVID-19 were retrospectively studied. Demographic characteristics, prevalence of VTE, site of occurrence, D-dimer variation over time, management, and outcomes were analyzed. RESULTS: During the study period, 484 confirmed cases of COVID-19 were admitted, 64 of which displayed VTE symptoms and 13 of which had confirmed symptomatic VTE(2.68% of total sample and 20.31% of symptomatic cases). Most cases (76.92%) occurred in intensive care. On the day attributed to VTE onset, D-dimer levels were over 3,000 ng/mL in 8 (80%) patients, a significant increase from baseline admission levels (p < 0.05). A significant decrease was also observed in D-dimer values at hospital discharge (p < 0.05). All patients received pharmacological thromboprophylaxis and/or anticoagulation as indicated. Two deaths occurred during the study, both patients with severe comorbidities. At the end of our study protocol, nine patients had been discharged and two remained hospitalized, but had no signs of VTE worsening. CONCLUSIONS: VTE prevalence in hospitalized COVID-19 patients was 2.7%, and higher in intensive care units. Early institution of prophylaxis and immediate full anticoagulation when VTE is diagnosed should be the goals of those who treat this kind of patient.

CONTEXTO: Os estados pró-trombóticos têm sido associados a infecções virais. A nova infecção pela síndrome respiratória aguda grave do coronavírus 2 (SARS-CoV-2) sabidamente eleva os níveis de D-dímero, embora a relação causal não tenha sido bem estabelecida. OBJETIVOS: Este estudo apresenta uma análise epidemiológica de episódios sintomáticos de tromboembolismo em um grupo de pacientes hospitalizados pela doença do novo coronavírus (COVID-19). MÉTODOS: Foi realizada uma revisão retrospectiva de prontuários de pacientes internados por COVID-19 que apresentaram trombose venosa profunda e/ou embolia pulmonar sintomáticas. Foram avaliados os dados demográficos, a prevalência de tromboembolismo, a variação do D-dímero ao longo do tempo, o manejo e os desfechos. RESULTADOS: Dos 484 casos confirmados de COVID-19 admitidos entre março e julho de 2020, 64 apresentaram sintomas de tromboembolismo, que foram investigados, e 13 tiveram tromboembolismo confirmado (2,68% do total e 20,31% dos sintomáticos). A maioria dos casos ocorreu em regime de terapia intensiva (76,92%). Houve um aumento significativo no número de pacientes com D-dímero acima de 3.000 ng/mL no dia atribuído ao diagnóstico de tromboembolismo com relação aos níveis do momento da admissão (80%, p < 0,05).Uma queda significativa de pacientes nesse limiar também foi observada no momento da alta (p < 0,05). Todos os pacientes receberam tromboprofilaxia ou anticoagulação conforme indicado. Houve dois óbitos na amostra, ambos pacientes com comorbidades severas. Ao fim do protocolo, nove pacientes receberam alta e dois permaneceram hospitalizados, mas sem sinais de piora. CONCLUSÕES: A prevalência de tromboembolismo em pacientes hospitalizados por COVID-19 foi de 2,7%, sendo mais frequente em regime de terapia intensiva. A instituição precoce de profilaxia e anticoagulação imediata ao diagnóstico é primordial nesse grupo de pacientes.

Evaluation of the Activity of Heparin Injected into the Fully Implantable Catheter for Chemotherapy (Portocath) between Two Moments of Use.

BACKGROUND: The aim of this study is to analyze whether heparin, used as a lock in fully implantable catheter for chemotherapy (portocath), maintains its activity even if it remains in the catheter for a long period of time. METHODS: According to the institutional protocol, all catheters routinely use the lock solution with 3 mL of heparinized solution after chemotherapy and the time interval between each change as lock in the catheters studied ranged from 7 to 30 days. A total of 25 blood samples from 22 patients with 6 types of neoplasia on chemotherapy or not were collected according to routine, and the 10 mL of liquid contained in the first aspirated reservoir/catheter (corresponding to the lock of the last section), were sent for laboratory analysis for prospectively studied with the following tests: anti-Xa, partially activated thromboplastin time (APTT), thrombin time (TT), reptilase, and thromboelastogram. RESULTS: Heparin activity was found in 96% of the anti-Xa and APTT tests. In relation to TT, 92% presented activity. The reptilase test was performed on 24 samples with significant time reduction in all of them. In the INTEM stage, the thromboelastometry test showed activity in 92% of samples and in the HEPTEM phase there was reduction in time in all samples. In all samples, the heparin activity was found to be independent of the time of use. CONCLUSIONS: We can conclude that lock of heparinized solution used in our service in fully implantable central venous catheters for chemotherapy was maintained with active heparin even after a long period of time (up to 30 days), demonstrating that the half-life of the substance within the catheter is greater than its plasma half-life.

COVID-19-associated coagulopathy and acute kidney injury in critically ill patients.

OBJECTIVE: The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. METHODS: Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. RESULTS: Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. CONCLUSION: Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

Low platelet reactivity in patients with myocardial infarction treated with aspirin plus ticagrelor.

OBJECTIVE: Low platelet reactivity levels are associated with higher risk of bleeding in patients receiving dual antiplatelet therapy relative to patients with optimal platelet blockade. This study set out to evaluate the prevalence of low platelet reactivity in patients with acute myocardial infarction treated with ticagrelor and aspirin. METHODS: Patients admitted with acute myocardial infarction who were already undergoing dual antiplatelet therapy with aspirin and ticagrelor were enrolled. Blood samples were collected 1 hour before and 2 hours after the maintenance dose of ticagrelor to investigate trough and the peak effects of the drug respectively. Platelet reactivity was measured by three methods: Multiplate®, PFA-100® with Innovance® PFA-P2Y cartridge and PFA-100® with Collagen/ADP cartridge. Platelet reactivity was assessed in the presence of peak levels of ticagrelor and defined according to previously validated cut-offs for each method (<19 AUC, >299 seconds and >116 seconds respectively). The level of significance was set at p<0.05. RESULTS: Fifty patients were enrolled (44% with ST-elevation). Median duration of DAPT was 3 days (interquartile range, 2-5 days). On average, peak and trough platelet reactivity were markedly low and did not differ between different methods. Low platelet reactivity was common, but varied according to analytic method (PFA-100®/Innovance®PFA-P2Y: 86%; Multiplate®: 74%; PFA-100®/Collagen/ADP: 48%; p<0.001). CONCLUSION: Low platelet reactivity was very common in patients with acute myocardial infarction submitted to dual antiplatelet therapy with ticagrelor and aspirin. Findings of this study justify the investigation of less intensive platelet inhibition strategies aimed at reducing the risk of bleeding in this population, such as lower dose regimens or monotherapy with P2Y12 inhibitors.

Clinical protocols for oral anticoagulant reversal during high risk of bleeding for emergency surgical and nonsurgical settings: a narrative review.

BACKGROUND AND OBJECTIVES: Oral anticoagulants prevent thromboembolic events but expose patients to a significant risk of bleeding due to the treatment itself, after trauma, or during surgery. Any physician working in the emergency department or involved in the perioperative care of a patient should be aware of the best reversal approach according to the type of drug and the patient's clinical condition. This paper presents a concise review and proposes clinical protocols for the reversal of oral anticoagulants in emergency settings, such as bleeding or surgery. CONTENTS: The authors searched for relevant studies in PubMed, LILACS, and the Cochrane Library database and identified 82 articles published up to September 2020 to generate a review and algorithms as clinical protocols for practical use. Hemodynamic status and the implementation of general supportive measures should be the first approach under emergency conditions. The drug type, dose, time of last intake, and laboratory evaluations of anticoagulant activity and renal function provide an estimation of drug clearance and should be taken into consideration. The reversal agents for vitamin K antagonists are 4-factor prothrombin complex concentrate and vitamin K, followed by fresh frozen plasma as a second-line treatment. Direct oral anticoagulants have specific reversal agents, such as andexanet alfa and idarucizumab, but are not widely available. Another possibility in this situation, but with less evidence, is prothrombin complex concentrates. CONCLUSION: The present algorithms propose a tool to help healthcare providers in the best decision making for patients under emergency conditions.

Thromboelastometry identifies coagulopathy associated with liver failure and disseminated intravascular coagulation caused by yellow fever, guiding specific hemostatic therapy: a case report. / A tromboelastometria identifica coagulopatia associada à insuficiência hepática e coagulação intravascular disseminada causadas por febre amarela, orientando a terapia hemostática específica: um relato de caso.

This case report a severe case of yellow fever complicated by liver failure and disseminated intravascular coagulation. Thromboelastometry was capable of identifying clotting disorders and guiding hemostatic therapy. We report the case of a 23-year-old male admitted to the Intensive Care Unit with sudden onset of fever, generalized muscle pain associated with liver failure, and disseminated intravascular coagulation. The results of conventional laboratory tests showed thrombocytopenia, whereas thromboelastometry suggested coagulopathy with slight hypofibrinogenemia, clotting factor consumption, and, consequently, an increased risk of bleeding. Unlike conventional laboratory tests, thromboelastometry identified the specific coagulation disorder and thereby guided hemostatic therapy. Both fibrinogen concentrates and vitamin K were administered, and no blood component transfusion was required, even in the presence of thrombocytopenia. Administration of hemostatic drugs, including fibrinogen concentrate and vitamin K, improved thromboelastometric parameters, correcting the complex coagulation disorder. Blood component transfusion was not performed, and there was no bleeding.

Este relato de caso detalha um caso grave de febre amarela complicada por insuficiência hepática e coagulação intravascular disseminada. A tromboelastometria foi capaz de identificar os distúrbios da coagulação e orientar o tratamento hemostático. Relatamos o caso de um homem com 23 anos de idade admitido na unidade de terapia intensiva com quadro com início abrupto de febre e dor muscular generalizada associados a insuficiência hepática e coagulação intravascular disseminada. Os resultados dos exames laboratoriais convencionais revelaram trombocitopenia, enquanto a tromboelastometria sugeriu coagulopatia com discreta hipofibrinogenemia, consumo de fatores de coagulação e, consequentemente, aumento do risco de sangramento. Diferentemente dos exames laboratoriais convencionais, a tromboelastometria identificou o distúrbio de coagulação específico e, assim, orientou o tratamento hemostático. Administraram-se concentrados de fibrinogênio e vitamina K, não sendo necessária a transfusão de qualquer componente do sangue, mesmo na presença de trombocitopenia. A tromboelastometria permitiu a identificação precoce da coagulopatia e ajudou a orientar a terapêutica hemostática. A administração de fármacos hemostáticos, incluindo concentrados de fibrinogênio e vitamina K, melhorou os parâmetros tromboelastométricos, com correção do transtorno da coagulação. Não se realizou transfusão de hemocomponentes, e não ocorreu qualquer sangramento.

Bleeding management after implementation of the Hemorrhage Code (Code H) at the Hospital Israelita Albert Einstein, São Paulo, Brazil.

Objective To describe the implementation of a care protocol based on rapid response teams, for management and resolution of bleeding. Methods A hospital protocol called Hemorrhage Code (Code H) was devised and developed. In a flow line, a multidisciplinary team provides comprehensive, fast and effective care to the patient with a severe hemorrhagic condition. In another flow line, professionals based at the hospital pharmacy focus on identifying patients at risk of bleeding, to avoid this event. Several hospital professionals and sectors were trained, each with specific roles, ensuring full support to the medical and nursing staffs. Results After implementing this protocol, we were able to significantly reduce the number of catastrophic events related to failure in bleeding management. Conclusion Code H is an example of a value-based medicine and precision medicine project by delivering comprehensive and multidisciplinary care, in addition to point-of-care testing introduced in clinical practice, optimizing patient safety and care practices at the hospital. Furthermore, it will be possible to minimize the risk of lawsuits for the hospital and physicians, as well as rationalizing resources with benefits for administrators and payers.

Gene Variants Associated With Venous Thrombosis: A Replication Study in a Brazilian Multicentre Study.

Single nucleotide polymorphisms (SNP) associated with Venous Thromboembolism (VTE) risk have been identified in European and American populations. Replicate SNPs associated with VTE in a Brazilian multicenter case-control study of the Southeast region. Patients with previous VTE assisted at the Outpatient Clinics of 3 centers of the Southeast Brazilian region were compared to normal controls of the same geographic region. We evaluated 29 SNPs associated with VTE risk in other populations, and 90 SNPs for stratification analysis of the population. Due to high admixture of Brazilian population and lack of previous studies, the calculation of the sample power was performed after genotyping. Sample size, allelic frequency and Hardy-Weinberg equilibrium were estimated. The association and odds ratio analyses were estimated by logistic regression and the results were adjusted for multiple tests using Bonferroni correction. The evaluation of the genetic structure similarity in the cases and controls was performed by AMOVA. 436 cases and 430 controls were included. It was demonstrated that this sample has a statistical power to detect a genetic association of 79.4%. AMOVA showed that the genetic variability between groups was 0.0% and 100% within each group. None of the SNPs showed association with VTE in our population. A Brazilian multicenter case-control study with adequate sample power, high genetic variability though no stratification between groups, showed no replication of SNPs associated with VTE. The high admixture of Brazilian population may be responsible for these results, emphasizing the influence of the population genetic structure in association studies.

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.

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection.

In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

Consensus on the investigation of thrombophilia in women and clinical management.

OBJECTIVE: To standardize the investigation and clinical management of women with laboratory and/or clinical abnormalities suggestive of thrombophilia, in order to optimize antithrombotic approach and indication of laboratory tests. METHODOLOGY: A discussion was carried out among 107 physicians (gynecologists/obstetricians, hematologists and vascular surgeons) present at a forum held at the Hospital Israelita Albert Einstein, in São Paulo (SP), Brazil. As a minimum criterion, 80% agreement was established in the voting to each recommendation of conduct in the final document. The cases in which there was agreement below 80% were discussed again, reaching a consensual agreement of conduct for the document writing. CONCLUSION: The standardization of an institutional consensus of suggestions of clinical approach contributes to a better management of the group to be evaluated and minimizes risks of intercurrent events. This was the first national consensus on the investigation of thrombophilia in women.

Thromboelastometry profile in critically ill patients: A single-center, retrospective, observational study.

BACKGROUND: Transfusion therapy is associated with increased morbidity, mortality and costs. Conventional coagulation tests (CCT) are weak bleeding predictors, poorly reflecting coagulation in vivo. Thromboelastometry (ROTEM) provides early identification of coagulation disorders and can guide transfusion therapy by goals, reducing blood components transfusion. OBJECTIVE: The aim of this study is to describe coagulation profile of critically ill patients using ROTEM and evaluate the association between CCT and thromboelastometry. METHODS: This is a retrospective, observational study conducted in medical-surgical intensive care unit (ICU). Adult patients (≥18 years) admitted to ICU between November 2012 and December 2014, in whom ROTEM analyses were performed for bleeding management were included in this study. The first ROTEM and CCT after ICU admission were recorded simultaneously. Additionally, we collected data on blood components transfusion and hemostatic agents immediately after laboratory tests results. RESULTS: The study included 531 patients. Most ROTEM tests showed normal coagulation profile [INTEM (54.8%), EXTEM (54.1%) and FIBTEM (53.3%)] with divergent results in relation to CCT: low platelet count (51.8% in INTEM and 55.9% in EXTEM); prolonged aPTT (69.9% in INTEM and 63.7% in EXTEM) and higher INR (23.8% in INTEM and 27.4% in EXTEM). However 16,7% of patients with normocoagulability in ROTEM received platelet concentrates and 10% fresh frozen plasma. CONCLUSION: The predominant ROTEM profile observed in this sample of critically ill patients was normal. In contrast, CCT suggested coagulopathy leading to a possibly unnecessary allogenic blood component transfusion. ROTEM test may avoid inappropriate allogeneic blood products transfusion in these patients.

COVID-19-associated coagulopathy and acute kidney injury in critically ill patients

ABSTRACT Objective The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. Methods Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. Results Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. Conclusion Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

A new era of thromboelastometry.

Severe hemorrhage with necessity of allogeneic blood transfusion is common complication in intensive care unit and is associated with increased morbidity and mortality. Prompt recognition and treatment of bleeding causes becomes essential for the effective control of hemorrhage, rationalizing the use of allogeneic blood components, and in this way, preventing an occurrence of their potential adverse effects. Conventional coagulation tests such as prothrombin time and activated partial thromboplastin time present limitations in predicting bleeding and guiding transfusion therapy in critically ill patients. Viscoelastic tests such as thromboelastography and rotational thromboelastometry allow rapid detection of coagulopathy and goal-directed therapy with specific hemostatic drugs. The new era of thromboelastometry relies on its efficacy, practicality, reproducibility and cost-effectiveness to establish itself as the main diagnostic tool and transfusion guide in patients with severe active bleeding.

Low platelet reactivity in patients with myocardial infarction treated with aspirin plus ticagrelor

ABSTRACT Objective: Low platelet reactivity levels are associated with higher risk of bleeding in patients receiving dual antiplatelet therapy relative to patients with optimal platelet blockade. This study set out to evaluate the prevalence of low platelet reactivity in patients with acute myocardial infarction treated with ticagrelor and aspirin. Methods: Patients admitted with acute myocardial infarction who were already undergoing dual antiplatelet therapy with aspirin and ticagrelor were enrolled. Blood samples were collected 1 hour before and 2 hours after the maintenance dose of ticagrelor to investigate trough and the peak effects of the drug respectively. Platelet reactivity was measured by three methods: Multiplate®, PFA-100® with Innovance® PFA-P2Y cartridge and PFA-100® with Collagen/ADP cartridge. Platelet reactivity was assessed in the presence of peak levels of ticagrelor and defined according to previously validated cut-offs for each method (<19 AUC, >299 seconds and >116 seconds respectively). The level of significance was set at p<0.05. Results: Fifty patients were enrolled (44% with ST-elevation). Median duration of DAPT was 3 days (interquartile range, 2-5 days). On average, peak and trough platelet reactivity were markedly low and did not differ between different methods. Low platelet reactivity was common, but varied according to analytic method (PFA-100®/Innovance®PFA-P2Y: 86%; Multiplate®: 74%; PFA-100®/Collagen/ADP: 48%; p<0.001). Conclusion: Low platelet reactivity was very common in patients with acute myocardial infarction submitted to dual antiplatelet therapy with ticagrelor and aspirin. Findings of this study justify the investigation of less intensive platelet inhibition strategies aimed at reducing the risk of bleeding in this population, such as lower dose regimens or monotherapy with P2Y12 inhibitors.

Determination of rivaroxaban in patient's plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS).

Rivaroxaban is an oral direct factor Xa inhibitor, therapeutically indicated in the treatment of thromboembolic diseases. As other new oral anticoagulants, routine monitoring of rivaroxaban is not necessary, but important in some clinical circumstances. In our study a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated to measure rivaroxaban plasmatic concentration. Our method used a simple sample preparation, protein precipitation, and a fast chromatographic run. It was developed a precise and accurate method, with a linear range from 2 to 500 ng/mL, and a lower limit of quantification of 4 pg on column. The new method was compared to a reference method (anti-factor Xa activity) and both presented a good correlation (r = 0.98, p < 0.001). In addition, we validated hemolytic, icteric or lipemic plasma samples for rivaroxaban measurement by HPLC-MS/MS without interferences. The chromogenic and HPLC-MS/MS methods were highly correlated and should be used as clinical tools for drug monitoring. The method was applied successfully in a group of 49 real-life patients, which allowed an accurate determination of rivaroxaban in peak and trough levels.

Incidence, diagnosis, treatment methods, and outcomes of clinically suspected venous thromboembolic disease in patients with COVID-19 in a quaternary hospital in Brazil / Incidência, diagnóstico, métodos terapêuticos e desfechos de eventos tromboembólicos venosos em pacientes com COVID-19 em um hospital quaternário do Brasil

Abstract Background Prothrombotic states have been associated with viral infections and the novel Sars-COV-2 infection has been associated with elevated D-dimer levels, although no causal relation has been clearly established. Objectives This study presents an epidemiological analysis of manifest VTE episodes in a group of patients hospitalized because of COVID-19. Methods Medical records of patients who presented symptomatic deep vein thrombosis and/or pulmonary embolism in concomitance with confirmed COVID-19 were retrospectively studied. Demographic characteristics, prevalence of VTE, site of occurrence, D-dimer variation over time, management, and outcomes were analyzed. Results During the study period, 484 confirmed cases of COVID-19 were admitted, 64 of which displayed VTE symptoms and 13 of which had confirmed symptomatic VTE(2.68% of total sample and 20.31% of symptomatic cases). Most cases (76.92%) occurred in intensive care. On the day attributed to VTE onset, D-dimer levels were over 3,000 ng/mL in 8 (80%) patients, a significant increase from baseline admission levels (p < 0.05). A significant decrease was also observed in D-dimer values at hospital discharge (p < 0.05). All patients received pharmacological thromboprophylaxis and/or anticoagulation as indicated. Two deaths occurred during the study, both patients with severe comorbidities. At the end of our study protocol, nine patients had been discharged and two remained hospitalized, but had no signs of VTE worsening. Conclusions VTE prevalence in hospitalized COVID-19 patients was 2.7%, and higher in intensive care units. Early institution of prophylaxis and immediate full anticoagulation when VTE is diagnosed should be the goals of those who treat this kind of patient.

Resumo Contexto Os estados pró-trombóticos têm sido associados a infecções virais. A nova infecção pela síndrome respiratória aguda grave do coronavírus 2 (SARS-CoV-2) sabidamente eleva os níveis de D-dímero, embora a relação causal não tenha sido bem estabelecida. Objetivos Este estudo apresenta uma análise epidemiológica de episódios sintomáticos de tromboembolismo em um grupo de pacientes hospitalizados pela doença do novo coronavírus (COVID-19). Métodos Foi realizada uma revisão retrospectiva de prontuários de pacientes internados por COVID-19 que apresentaram trombose venosa profunda e/ou embolia pulmonar sintomáticas. Foram avaliados os dados demográficos, a prevalência de tromboembolismo, a variação do D-dímero ao longo do tempo, o manejo e os desfechos. Resultados Dos 484 casos confirmados de COVID-19 admitidos entre março e julho de 2020, 64 apresentaram sintomas de tromboembolismo, que foram investigados, e 13 tiveram tromboembolismo confirmado (2,68% do total e 20,31% dos sintomáticos). A maioria dos casos ocorreu em regime de terapia intensiva (76,92%). Houve um aumento significativo no número de pacientes com D-dímero acima de 3.000 ng/mL no dia atribuído ao diagnóstico de tromboembolismo com relação aos níveis do momento da admissão (80%, p < 0,05).Uma queda significativa de pacientes nesse limiar também foi observada no momento da alta (p < 0,05). Todos os pacientes receberam tromboprofilaxia ou anticoagulação conforme indicado. Houve dois óbitos na amostra, ambos pacientes com comorbidades severas. Ao fim do protocolo, nove pacientes receberam alta e dois permaneceram hospitalizados, mas sem sinais de piora. Conclusões A prevalência de tromboembolismo em pacientes hospitalizados por COVID-19 foi de 2,7%, sendo mais frequente em regime de terapia intensiva. A instituição precoce de profilaxia e anticoagulação imediata ao diagnóstico é primordial nesse grupo de pacientes.

A tromboelastometria identifica coagulopatia associada à insuficiência hepática e coagulação intravascular disseminada causadas por febre amarela, orientando a terapia hemostática específica: um relato de caso / Thromboelastometry identifies coagulopathy associated with liver failure and disseminated intravascular coagulation caused by yellow fever, guiding specific hemostatic therapy: a case report

RESUMO Este relato de caso detalha um caso grave de febre amarela complicada por insuficiência hepática e coagulação intravascular disseminada. A tromboelastometria foi capaz de identificar os distúrbios da coagulação e orientar o tratamento hemostático. Relatamos o caso de um homem com 23 anos de idade admitido na unidade de terapia intensiva com quadro com início abrupto de febre e dor muscular generalizada associados a insuficiência hepática e coagulação intravascular disseminada. Os resultados dos exames laboratoriais convencionais revelaram trombocitopenia, enquanto a tromboelastometria sugeriu coagulopatia com discreta hipofibrinogenemia, consumo de fatores de coagulação e, consequentemente, aumento do risco de sangramento. Diferentemente dos exames laboratoriais convencionais, a tromboelastometria identificou o distúrbio de coagulação específico e, assim, orientou o tratamento hemostático. Administraram-se concentrados de fibrinogênio e vitamina K, não sendo necessária a transfusão de qualquer componente do sangue, mesmo na presença de trombocitopenia. A tromboelastometria permitiu a identificação precoce da coagulopatia e ajudou a orientar a terapêutica hemostática. A administração de fármacos hemostáticos, incluindo concentrados de fibrinogênio e vitamina K, melhorou os parâmetros tromboelastométricos, com correção do transtorno da coagulação. Não se realizou transfusão de hemocomponentes, e não ocorreu qualquer sangramento.

Abstract This case report a severe case of yellow fever complicated by liver failure and disseminated intravascular coagulation. Thromboelastometry was capable of identifying clotting disorders and guiding hemostatic therapy. We report the case of a 23-year-old male admitted to the Intensive Care Unit with sudden onset of fever, generalized muscle pain associated with liver failure, and disseminated intravascular coagulation. The results of conventional laboratory tests showed thrombocytopenia, whereas thromboelastometry suggested coagulopathy with slight hypofibrinogenemia, clotting factor consumption, and, consequently, an increased risk of bleeding. Unlike conventional laboratory tests, thromboelastometry identified the specific coagulation disorder and thereby guided hemostatic therapy. Both fibrinogen concentrates and vitamin K were administered, and no blood component transfusion was required, even in the presence of thrombocytopenia. Administration of hemostatic drugs, including fibrinogen concentrate and vitamin K, improved thromboelastometric parameters, correcting the complex coagulation disorder. Blood component transfusion was not performed, and there was no bleeding.

Bleeding management after implementation of the Hemorrhage Code (Code H) at the Hospital Israelita Albert Einstein, São Paulo, Brazil / Manejo de sangramento após implantação do Código Hemorrágico (Código H) no Hospital Israelita Albert Einstein, São Paulo, Brasil

ABSTRACT Objective To describe the implementation of a care protocol based on rapid response teams, for management and resolution of bleeding. Methods A hospital protocol called Hemorrhage Code (Code H) was devised and developed. In a flow line, a multidisciplinary team provides comprehensive, fast and effective care to the patient with a severe hemorrhagic condition. In another flow line, professionals based at the hospital pharmacy focus on identifying patients at risk of bleeding, to avoid this event. Several hospital professionals and sectors were trained, each with specific roles, ensuring full support to the medical and nursing staffs. Results After implementing this protocol, we were able to significantly reduce the number of catastrophic events related to failure in bleeding management. Conclusion Code H is an example of a value-based medicine and precision medicine project by delivering comprehensive and multidisciplinary care, in addition to point-of-care testing introduced in clinical practice, optimizing patient safety and care practices at the hospital. Furthermore, it will be possible to minimize the risk of lawsuits for the hospital and physicians, as well as rationalizing resources with benefits for administrators and payers.

RESUMO Objetivo Descrever a implantação de um protocolo de atendimento nos moldes de times de resposta rápida, para manejo e resolução do sangramento. Métodos Foi idealizado e desenvolvido um protocolo institucional, chamado Código Hemorrágico, ou Código H, no qual, em um fluxo, um time multiprofissional e multidisciplinar foi constituído para atendimento integral, rápido e eficaz do paciente com doença hemorrágica grave. Em um outro fluxo, os profissionais, centralizados na farmácia do hospital, focavam na identificação do paciente com risco de hemorragia, no sentido de evitar o evento. Vários profissionais e setores do hospital foram treinados, e cada um, com funções específicas, deveria oferecer garantia total de apoio e suporte às equipes médica e de enfermagem. Resultados Após a implementação do protocolo, o número de eventos catastróficos relacionados à falha no manejo do sangramento reduziu significativamente. Conclusão O Código H é um exemplo de projeto de medicina baseada em valor e de medicina de precisão, por meio de atendimento integral e multidisciplinar, além de testes point of care introduzidos na prática clínica, com otimização da segurança do paciente e da prática assistencial na instituição. Ainda, por meio dele, deve ser possível minimizar o risco de ações judiciais para o hospital e os médicos, além de racionalizar recursos, com benefícios para administradores e fontes pagadoras.