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1.
Trials ; 22(1): 202, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691765

RESUMO

OBJECTIVES: To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days. TRIAL DESIGN: Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial PARTICIPANTS: The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Participants are recruited from hospital sites in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and the United States of America. The inclusion criteria are: 1) Laboratory confirmed COVID-19 (diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification) prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission; 2) Admitted to hospital for COVID-19; 3) One D-dimer value above the upper limit of normal (ULN) (within 5 days (i.e. 120 hours) of hospital admission) AND EITHER: a. D-Dimer ≥2 times ULN OR b. D-Dimer above ULN and Oxygen saturation ≤ 93% on room air; 4) > 18 years of age; 5) Informed consent from the patient (or legally authorized substitute decision maker). The exclusion criteria are: 1) pregnancy; 2) hemoglobin <80 g/L in the last 72 hours; 3) platelet count <50 x 109/L in the last 72 hours; 4) known fibrinogen <1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 5) known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 6) patient already prescribed intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration); 7) patient already prescribed therapeutic anticoagulation at the time of screening [low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban)]; 8) patient prescribed dual antiplatelet therapy, when one of the agents cannot be stopped safely; 9) known bleeding within the last 30 days requiring emergency room presentation or hospitalization; 10) known history of a bleeding disorder of an inherited or active acquired bleeding disorder; 11) known history of heparin-induced thrombocytopenia; 12) known allergy to UFH or LMWH; 13) admitted to the intensive care unit at the time of screening; 14) treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening; 15) Imminent death according to the judgement of the most responsible physician; 16) enrollment in another clinical trial of antithrombotic therapy involving hospitalized patients. INTERVENTION AND COMPARATOR: Intervention: Therapeutic dose of LMWH (dalteparin, enoxaparin, tinzaparin) or high dose nomogram of UFH. The choice of LMWH versus UFH will be at the clinician's discretion and dependent on local institutional supply. Comparator: Standard care [thromboprophylactic doses of LMWH (dalteparin, enoxaparin, tinzaparin, fondaparinux)] or UFH. Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is generally considered standard care. MAIN OUTCOMES: The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Secondary outcomes include (evaluated up to day 28): 1. All-cause death 2. Composite of ICU admission or all-cause death 3. Composite of mechanical ventilation or all-cause death 4. Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation; 5. Red blood cell transfusion (>1 unit); 6. Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; 7. Renal replacement therapy; 8. Hospital-free days alive; 9. ICU-free days alive; 10. Ventilator-free days alive; 11. Organ support-free days alive; 12. Venous thromboembolism (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 13. Arterial thromboembolism (defined as suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 14. Heparin induced thrombocytopenia; 15. Trajectories of COVID-19 disease-related coagulation and inflammatory biomarkers. RANDOMISATION: Randomisation will be stratified by site and age (>65 versus ≤65 years) using a 1:1 computer-generated random allocation sequence with variable block sizes. Randomization will occur within the first 5 days (i.e. 120 hours) of participant hospital admission. However, it is recommended that randomization occurs as early as possible after hospital admission. Central randomization using an interactive web response system will ensure allocation concealment. BLINDING (MASKING): No blinding involved. This is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 462 patients (231 per group) are needed to detect a 15% risk difference, from 50% in the control group to 35% in the experimental group, with power of 90% at a two-sided alpha of 0.05. TRIAL STATUS: Protocol Version Number 1.4. Recruitment began on May 11th, 2020. Recruitment is expected to be completed March 2022. Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04362085 Date of Trial Registration: April 24, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , /tratamento farmacológico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , /complicações , Ensaios Clínicos Fase III como Assunto , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Hospitalização , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Ventilação não Invasiva/estatística & dados numéricos , Ensaios Clínicos Pragmáticos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos
2.
Sci Rep ; 11(1): 4432, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627696

RESUMO

Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46-65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.


Assuntos
Transtornos da Coagulação Sanguínea/virologia , Traumatismos Cardíacos/virologia , Idoso , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/epidemiologia , /fisiopatologia , China/epidemiologia , Estudos de Coortes , Creatina Quinase Forma MB/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/epidemiologia , Traumatismos Cardíacos/fisiopatologia , Hemoglobinas/metabolismo , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Troponina I/sangue
3.
Expert Rev Hematol ; 14(2): 155-173, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33480807

RESUMO

INTRODUCTION: COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management. AREAS COVERED: Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Coagulopathy', and 'D-dimer'. Twenty-two studies were taken for weighted pooled analysis of D-dimer. EXPERT OPINION: A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Ativação do Complemento , Animais , Anticoagulantes/uso terapêutico , Biomarcadores , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Testes de Coagulação Sanguínea , /imunologia , China/epidemiologia , Comorbidade , Infecções por Coronavirus/sangue , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/epidemiologia , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/fisiopatologia , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Previsões , Humanos , Imunização Passiva , Inflamação/etiologia , Inflamação/fisiopatologia , Quelantes de Ferro/uso terapêutico , Isquemia/sangue , Isquemia/etiologia , Isquemia/fisiopatologia , Camundongos , Prevalência , Síndrome Respiratória Aguda Grave/sangue , Índice de Gravidade de Doença , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombofilia/fisiopatologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/fisiopatologia
4.
Eur Rev Med Pharmacol Sci ; 25(1): 518-522, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33506943

RESUMO

OBJECTIVE: From the beginning of the novel coronavirus infection (COVID-19) pandemic in the world, much efforts have been accomplished to explain a precise clinical feature for the disease and to find the best therapeutic approach for the patients. Although coagulation abnormalities have found in novel coronavirus infection (COVID-19) patients, still little is known about the association between the disease and changes in coagulation parameters. Our purpose is to evaluate the differences between the coagulation parameters between COVID-19 patients and healthy counterparts. PATIENTS AND METHODS: 63 patients with confirmed COVID-19 infection were admitted to the present study. We evaluated coagulation value in these patients and in 40 healthy individuals. RESULTS: We found that although there was no significant difference between PT and PTT values in patients and healthy counterparts, the fibrinogen values in patients were higher than the control group (p < 0.05). Moreover, the values of fibrin/fibrinogen degradation products (FDP) and D-dimer in all COVID-19 cases were considerably higher than those in control people (p < 0.05). Of note, FDP and D-dimer in patients with regular COVID-19 infection were lower than patients with severe forms. CONCLUSIONS: It seems that the conduction of routine blood coagulation test could be a beneficial supplementary approach for early diagnosis of COVID-19. In addition, our study shed more light on the therapeutic value of anti-coagulant-based treatment for COVID-19 patients, especially for those with severe type of the disease.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/prevenção & controle , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Transtornos da Coagulação Sanguínea/etiologia , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Técnicas de Laboratório Clínico , Feminino , Humanos , Masculino , Valor Preditivo dos Testes
5.
Cardiol Rev ; 29(1): 43-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32947478

RESUMO

The novel coronavirus (severe acute respiratory syndrome CoV-2 [SARS-CoV-2]), also known as COVID-19, is a single-stranded enveloped RNA virus that created a Public Health Emergency of International Concern in January 2020, with a global case burden of over 15 million in just 7 months. Infected patients develop a wide range of clinical manifestations-typically presenting with fever, cough, myalgia, and fatigue. Severely ill patients may fall victim to acute respiratory distress syndrome, acute heart injuries, neurological manifestations, or complications due to secondary infections. These critically ill patients are also found to have disrupted coagulation function, predisposing them to consumptive coagulopathies, and both venous and thromboembolic complications. Common laboratory findings include thrombocytopenia, elevated D-dimer, fibrin degradation products, and fibrinogen, all of which have been associated with greater disease severity. Many cases of pulmonary embolism have been noted, along with deep vein thrombosis, ischemic stroke, myocardial infarction, and systemic arterial embolism. The pathogenesis of coronavirus has not been completely elucidated, but the virus is known to cause excessive inflammation, endothelial injury, hypoxia, and disseminated intravascular coagulation, all of which contribute to thrombosis formation. These patients are also faced with prolonged immobilization while staying in the hospital or intensive care unit. It is important to have a high degree of suspicion for thrombotic complications as patients may rapidly deteriorate in severe cases. Evidence suggests that prophylaxis with anticoagulation may lead to a lower risk of mortality, although it does not eliminate the possibility. The risks and benefits of anticoagulation treatment should be considered in each case. Patients should be regularly evaluated for bleeding risks and thrombotic complications.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Embolia/sangue , Trombose/sangue , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/metabolismo , /tratamento farmacológico , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/metabolismo , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/metabolismo , Coagulação Intravascular Disseminada/prevenção & controle , Embolia/etiologia , Embolia/metabolismo , Embolia/prevenção & controle , Endotélio Vascular/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Hipóxia/metabolismo , Imobilização , Inflamação/sangue , Inflamação/etiologia , Inflamação/metabolismo , /etiologia , /prevenção & controle , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Guias de Prática Clínica como Assunto , Embolia Pulmonar/sangue , Embolia Pulmonar/etiologia , Embolia Pulmonar/metabolismo , Embolia Pulmonar/prevenção & controle , Índice de Gravidade de Doença , Trombocitopenia/sangue , Trombocitopenia/etiologia , Trombose/etiologia , Trombose/metabolismo , Trombose/prevenção & controle , Trombose Venosa/sangue , Trombose Venosa/etiologia , Trombose Venosa/metabolismo
6.
Eur Rev Med Pharmacol Sci ; 24(23): 12466-12479, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336766

RESUMO

OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. PATIENTS AND METHODS: Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. RESULTS: At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p  = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). CONCLUSIONS: SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/sangue , /sangue , Tromboelastografia , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/sangue , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Testes de Coagulação Sanguínea , Enoxaparina/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Heparina/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Estudos Prospectivos , Resultado do Tratamento
7.
JAMA ; 324(14): 1419-1428, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048155

RESUMO

Importance: Coagulopathy may deter physicians from performing a lumbar puncture. Objective: To determine the risk of spinal hematoma after lumbar puncture in patients with and without coagulopathy. Design, Setting, and Participants: Danish nationwide, population-based cohort study using medical registries to identify persons who underwent lumbar puncture and had cerebrospinal fluid analysis (January 1, 2008-December 31, 2018; followed up through October 30, 2019). Coagulopathy was defined as platelets lower than 150 × 109/L, international normalized ratio (INR) greater than 1.4, or activated partial thromboplastin time (APTT) longer than 39 seconds. Exposures: Coagulopathy at the time of lumbar puncture. Main Outcomes and Measures: Thirty-day risk of spinal hematoma. Risks were provided as numbers and percentages with 95% CIs. Secondary analyses included risks of traumatic lumbar puncture (>300 × 106 erythrocytes/L after excluding patients diagnosed with subarachnoid hemorrhage). Adjusted hazard rate ratios (HRs) were computed using Cox regression models. Results: A total of 83 711 individual lumbar punctures were identified among 64 730 persons (51% female; median age, 43 years [interquartile range, 22-62 years]) at the time of the procedure. Thrombocytopenia was present in 7875 patients (9%), high INR levels in 1393 (2%), and prolonged APTT in 2604 (3%). Follow-up was complete for more than 99% of the study participants. Overall, spinal hematoma occurred within 30 days for 99 of 49 526 patients (0.20%; 95% CI, 0.16%-0.24%) without coagulopathy vs 24 of 10 371 patients (0.23%; 95% CI, 0.15%-0.34%) with coagulopathy. Independent risk factors for spinal hematoma were male sex (adjusted hazard ratio [HR], 1.72; 95% CI, 1.15-2.56), those aged 41 through 60 years (adjusted HR, 1.96; 95% CI, 1.01-3.81) and those aged 61 through 80 years (adjusted HR, 2.20; 95% CI, 1.12-4.33). Risks did not increase significantly according to overall severity of coagulopathy, in subgroup analyses of severity of coagulopathy by pediatric specialty or medical indication (infection, neurological condition, and hematological malignancy), nor by cumulative number of procedures. Traumatic lumbar punctures occurred more frequently among patients with INR levels of 1.5 to 2.0 (36.8%; 95% CI, 33.3%-40.4%), 2.1 to 2.5 (43.7%; 95% CI, 35.8%-51.8%), and 2.6 to 3.0 (41.9% 95% CI 30.5-53.9) vs those with normal INR (28.2%; 95% CI, 27.7%-28.75%). Traumatic spinal tap occurred more often in patients with an APTT of 40 to 60 seconds (26.3%; 95% CI, 24.2%-28.5%) vs those with normal APTT (21.3%; 95% CI, 20.6%-21.9%) yielding a risk difference of 5.1% (95% CI, 2.9%-7.2%). Conclusions and Relevance: In this Danish cohort study, risk of spinal hematoma following lumbar puncture was 0.20% among patients without coagulopathy and 0.23% among those with coagulopathy. Although these findings may inform decision-making about lumbar puncture by describing rates in this sample, the observed rates may reflect bias due to physicians selecting relatively low-risk patients for lumbar puncture.


Assuntos
Transtornos da Coagulação Sanguínea/complicações , Hematoma/etiologia , Doenças da Coluna Vertebral/etiologia , Punção Espinal/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Coagulação Sanguínea/sangue , Líquido Cefalorraquidiano/química , Criança , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Punção Espinal/estatística & dados numéricos , Trombocitopenia/epidemiologia , Fatores de Tempo , Adulto Jovem
8.
Clin Appl Thromb Hemost ; 26: 1076029620964868, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33030047

RESUMO

To discuss the coagulation dysfunction in COVID-19 patients and to find new biomarkers to separate severe COVID-19 patients from mild ones. We use a retrospective analysis of 88 COVID-19 patients, and compare the coagulation function between severe and mild groups. We found the prothrombin time (PT), thrombin time (TT), D-dimer were significantly higher in the severe group (P < 0.05), and the highest area under the curve (AUC) is 0.91 for D-dimer, while the AUC of PT and TT were 0.80 and 0.61 respectively. We identified that D-dimer has a better value in predicting patients who are likely to develop into severe cases, with the sensitivity and specificity were 84.4% and 88.8%, respectively. D-dimer may be a good biomarker to separate the severe COVID-19 patients from the mild ones.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Testes de Coagulação Sanguínea/métodos , Infecções por Coronavirus/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Pneumonia Viral/complicações , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/fisiopatologia , China , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Valor Preditivo dos Testes , Tempo de Protrombina , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Tempo de Trombina
9.
Semin Thromb Hemost ; 46(7): 807-814, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32882720

RESUMO

The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a "perfect storm," where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.


Assuntos
Coagulação Sanguínea , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Exercício Físico , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Infecções por Coronavirus/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinólise , Hemostasia , Humanos , Inflamação , Pandemias , Pneumonia Viral/complicações , Risco , Trombose/sangue , Trombose/complicações
10.
BMC Pregnancy Childbirth ; 20(1): 511, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887569

RESUMO

BACKGROUND: It has been proposed that pregnant women and their fetuses may be particularly at risk for poor outcomes due to the coronavirus (COVID-19) pandemic. From the few case series that are available in the literature, women with high risk pregnancies have been associated with higher morbidity. It has been suggested that pregnancy induced immune responses and cardio-vascular changes can exaggerate the course of the COVID-19 infection. CASE PRESENTATION: A 26-year old Somalian woman (G2P1) presented with a nine-day history of shortness of breath, dry cough, myalgia, nausea, abdominal pain and fever. A nasopharyngeal swab returned positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Her condition rapidly worsened leading to severe liver and coagulation impairment. An emergency Caesarean section was performed at gestational week 32 + 6 after which the patient made a rapid recovery. Severe COVID-19 promptly improved by the termination of the pregnancy or atypical HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelet Count) exacerbated by concomitant COVID-19 infection could not be ruled out. There was no evidence of vertical transmission. CONCLUSIONS: This case adds to the growing body of evidence which raises concerns about the possible negative maternal outcomes of COVID-19 infection during pregnancy and advocates for pregnant women to be recognized as a vulnerable group during the current pandemic.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Cesárea , Infecções por Coronavirus/sangue , Hepatopatias/sangue , Obesidade Materna , Pneumonia Viral/sangue , Complicações Infecciosas na Gravidez/sangue , Adulto , Antitrombina III/metabolismo , Índice de Apgar , Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/fisiopatologia , Diagnóstico Diferencial , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Síndrome HELLP/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , L-Lactato Desidrogenase/sangue , Hepatopatias/etiologia , Pulmão/diagnóstico por imagem , Masculino , Pandemias , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/fisiopatologia , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Suécia , Tomografia Computadorizada por Raios X
13.
J Thromb Haemost ; 18(9): 2138-2144, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881336

RESUMO

Hypercoagulability is an increasingly recognized complication of SARS-CoV-2 infection. As such, anticoagulation has become part and parcel of comprehensive COVID-19 management. However, several uncertainties exist in this area, including the appropriate type and dose of heparin. In addition, special patient populations, including those with high body mass index and renal impairment, require special consideration. Although the current evidence is still insufficient, we provide a pragmatic approach to anticoagulation in COVID-19, but stress the need for further trials in this area.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/mortalidade , Transtornos da Coagulação Sanguínea/virologia , Tomada de Decisão Clínica , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Fatores de Risco , Resultado do Tratamento
14.
J Thromb Thrombolysis ; 50(4): 825-832, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32761495

RESUMO

The new outbreak of Coronavirus Disease 2019 (COVID-19) has emerged as a serious global public health concern. A more in-depth study of blood coagulation abnormality is needed. We retrospectively analyzed 147 consecutive patients with COVID-19 who were admitted to three ICUs in Wuhan from February 9th, 2020 to March 20th, 2020. The baseline coagulation and other characteristics were studied. Our results showed that the prolonged PT, FDP, DD were positively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, multi-inflammation cytokines, and negatively correlated with the lymphocytes level (p < 0.01). The level of ATIII was significantly negatively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, IL2R, IL6 and IL8 (p < 0.05). The patients in the ARDS group had a more prominent abnormality in PT, FDP, DD and ATIII, while the patients in the AKI group had more prolonged PT, more severe FDP and DD level, more inferior ATIII and Fib level than those in the non-AKI group (p < 0.01). The value of PT, DD and FDP were positively correlated with the classical APACHE II, SOFA and qSOFA scores, while the ATIII was negatively correlated with them (p < 0.001). The high levels of PT, FDP and DD were correlated with in-hospital mortality (p < 0.001). In conclusion, blood coagulation disorder was prominent in ICU patients with COVID-19 and was correlated with multi-inflammation factors. The abnormality of blood coagulation parameters could be an adverse prognostic indicator for ICU patients with COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/virologia , Coagulação Sanguínea , Infecções por Coronavirus/terapia , Mediadores da Inflamação/sangue , Inflamação/virologia , Unidades de Terapia Intensiva , Pneumonia Viral/terapia , Idoso , Antitrombina III/metabolismo , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/mortalidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Mortalidade Hospitalar , Interações Hospedeiro-Patógeno , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
15.
Elife ; 92020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32804081

RESUMO

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.


Assuntos
Betacoronavirus/isolamento & purificação , Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea , Coagulação Sanguínea , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Fibrinogênio/metabolismo , Interações entre Hospedeiro e Microrganismos , Humanos , Contagem de Leucócitos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo
17.
BMC Pregnancy Childbirth ; 20(1): 481, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838744

RESUMO

BACKGROUND: The world's understanding of COVID-19 continues to evolve as the scientific community discovers unique presentations of this disease. This case report depicts an unexpected intraoperative coagulopathy during a cesarean section in an otherwise asymptomatic patient who was later found to have COVID-19. This case suggests that there may be a higher risk for intrapartum bleeding in the pregnant, largely asymptomatic COVID-positive patient with more abnormal COVID laboratory values. CASE: The case patient displayed D-Dimer elevations beyond what is typically observed among this hospital's COVID-positive peripartum population and displayed significantly more oozing than expected intraoperatively, despite normal prothrombin time, international normalized ratio, fibrinogen, and platelets. CONCLUSION: There is little published evidence on the association between D-Dimer and coagulopathy among the pregnant population infected with SARS-CoV-2. This case report contributes to the growing body of evidence on the effects of COVID-19 in pregnancy. A clinical picture concerning for intraoperative coagulopathy may be associated with SARS-CoV-2 infection during cesarean sections, and abnormal COVID laboratory tests, particularly D-Dimer, may help identify the patients in which this presentation occurs.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Perda Sanguínea Cirúrgica , Apresentação Pélvica/cirurgia , Cesárea , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Complicações Hematológicas na Gravidez/sangue , Complicações Infecciosas na Gravidez/sangue , Adulto , Antifibrinolíticos/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/metabolismo , Proteína C-Reativa/metabolismo , Cauterização , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/metabolismo , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Hemostasia Cirúrgica , Humanos , Coeficiente Internacional Normatizado , Metilergonovina/uso terapêutico , Oligo-Hidrâmnio , Ocitócicos/uso terapêutico , Ocitocina/uso terapêutico , Pandemias , Contagem de Plaquetas , Pneumonia Viral/diagnóstico , Pneumonia Viral/metabolismo , Gravidez , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Hematológicas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/metabolismo , Tempo de Protrombina , Ácido Tranexâmico/uso terapêutico , Inércia Uterina/tratamento farmacológico
18.
Arterioscler Thromb Vasc Biol ; 40(9): 2033-2044, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32657623

RESUMO

The world is amid a pandemic caused by severe acute respiratory syndrome-coronavirus 2. Severe acute respiratory syndrome-coronavirus causes serious respiratory tract infections that can lead to viral pneumonia, acute respiratory distress syndrome, and death. Some patients with coronavirus disease 2019 (COVID-19) have an activated coagulation system characterized by elevated plasma levels of d-dimer-a biomarker of fibrin degradation. Importantly, high levels of D-dimer on hospital admission are associated with increased risk of mortality. Venous thromboembolism is more common than arterial thromboembolism in hospitalized COVID-19 patients. Pulmonary thrombosis and microvascular thrombosis are observed in autopsy studies, and this may contribute to the severe hypoxia observed in COVID-19 patients. It is likely that multiple systems contribute to thrombosis in COVID-19 patients, such as activation of coagulation, platelet activation, hypofibrinolysis, endothelial cell dysfunction, inflammation, neutrophil extracellular traps, and complement. Targeting these different pathways may reduce thrombosis and improve lung function in COVID-19 patients.


Assuntos
Betacoronavirus , Transtornos da Coagulação Sanguínea/complicações , Coagulação Sanguínea , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Trombose/etiologia , Transtornos da Coagulação Sanguínea/sangue , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/epidemiologia , Trombose/sangue
19.
Neurol India ; 68(3): 560-572, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32643664

RESUMO

COVID-19, in most patients, presents with mild flu-like illness. Elderly patients with comorbidities, like hypertension, diabetes, or lung and cardiac disease, are more likely to have severe disease and deaths. Neurological complications are frequently reported in severely or critically ill patients with comorbidities. In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The SARS-CoV-2 virus enters the brain either via a hematogenous route or olfactory system. Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Nonspecific headache is a commonly experienced neurological symptom. A new type of headache "personal protection equipment-related headache" has been described. Complete or partial anosmia and ageusia are common peripheral nervous system manifestations. Recently, many cases of Guillain-Barré syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. Guillain-Barré syndrome does respond to intravenous immunoglobulin. Myalgia/fatigue is also common, and elevated creatine kinase levels indicate muscle injury. Most of the reports about neurological complications are currently from China. COVID-19 pandemic is spreading to other parts of the world; the spectrum of neurological complications is likely to widen further.


Assuntos
Ageusia/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/imunologia , Encefalite/fisiopatologia , Síndrome de Guillain-Barré/fisiopatologia , Cefaleia/fisiopatologia , Transtornos do Olfato/fisiopatologia , Pneumonia Viral/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Ageusia/etiologia , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Barreira Hematoencefálica , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/fisiopatologia , Coma/etiologia , Coma/fisiopatologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Delírio/etiologia , Delírio/fisiopatologia , Encefalite/etiologia , Encefalite/imunologia , Encefalomielite Aguda Disseminada/etiologia , Encefalomielite Aguda Disseminada/imunologia , Encefalomielite Aguda Disseminada/fisiopatologia , Fadiga/etiologia , Fadiga/fisiopatologia , Síndrome de Guillain-Barré/etiologia , Cefaleia/etiologia , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/fisiopatologia , Leucoencefalite Hemorrágica Aguda/etiologia , Leucoencefalite Hemorrágica Aguda/imunologia , Leucoencefalite Hemorrágica Aguda/fisiopatologia , Mialgia/etiologia , Mialgia/fisiopatologia , Transtornos do Olfato/etiologia , Pandemias , Equipamento de Proteção Individual/efeitos adversos , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/imunologia
20.
Paediatr Respir Rev ; 35: 20-24, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32653469

RESUMO

Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism. In addition, autopsy studies have revealed co-localized thrombosis and inflammation, which is the signature of thromboinflammation, within the pulmonary capillary vasculature. While the majority of published data is on adult patients, there are parallels to pediatric patients. In our experience as a COVID-19 epicenter, children and young adults do develop both the coagulopathy and the ALI of COVID-19. This review will discuss COVID-19 ALI from a hematological perspective with discussion of the distinct aspects of coagulation that are apparent in COVID-19. Current and potential interventions targeting the multiple thromboinflammatory mechanisms will be discussed.


Assuntos
Lesão Pulmonar Aguda/sangue , Infecções por Coronavirus/sangue , Inflamação/sangue , Pneumonia Viral/sangue , Trombose/sangue , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/fisiopatologia , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Capilares/imunologia , Capilares/fisiopatologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Inibidores do Fator Xa/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Pandemias , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Embolia Pulmonar/sangue , Embolia Pulmonar/imunologia , Embolia Pulmonar/fisiopatologia , Trombina/imunologia , Trombina/metabolismo , Trombose/tratamento farmacológico , Trombose/imunologia , Trombose/fisiopatologia
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