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1.
PLoS One ; 16(1): e0245565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481902

RESUMO

BACKGROUND AND AIMS: Several studies reported a high incidence of pulmonary embolism (PE) among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but detailed data about clinical characteristics, risk factors of these patients and prognostic role of PE are still lacking. We aim to evaluate the occurrence of pulmonary embolism among patients with SARS-CoV-2 infection, and to describe their risk factors, clinical characteristics, and in-hospital clinical outcomes. METHODS: This is a multicenter Italian study including 333 consecutive SARS-CoV-2 patients admitted to seven hospitals from February 22 to May 15, 2020. All the patients underwent computed tomography pulmonary angiography (CTPA) for PE detection. In particular, CTPA was performed in case of inadequate response to high-flow oxygen therapy (Fi02≥0.4 to maintain Sp02≥92%), elevated D-dimer (>0.5µg/mL), or echocardiographic signs of right ventricular dysfunction. Clinical, laboratory and radiological data were also analyzed. RESULTS: Among 333 patients with laboratory confirmed SARS-CoV-2 pneumonia and undergoing CTPA, PE was detected in 109 (33%) cases. At CTPA, subsegmental, segmental, lobar and central thrombi were detected in 31 (29%), 50 (46%), 20 (18%) and 8 (7%) cases, respectively. In-hospital death occurred in 29 (27%) patients in the PE-group and in 47 (21%) patients in the non-PE group (p = 0.25). Patients in PE-group had a low rate of traditional risk factors and deep vein thrombosis was detected in 29% of patients undergoing compression ultrasonography. In 71% of cases with documented PE, the thrombotic lesions were located in the correspondence of parenchymal consolidation areas. CONCLUSIONS: Despite a low rate of risk factors for venous thromboembolism, PE is present in about 1 out 3 patients with SARS-CoV-2 pneumonia undergoing CTPA for inadequate response to oxygen therapy, elevated D-dimer level, or echocardiographic signs of right ventricular dysfunction. In most of the cases, the thromboses were located distally in the pulmonary tree and were mainly confined within pneumonia areas.


Assuntos
/complicações , Embolia Pulmonar/etiologia , Doença Aguda , Idoso , /diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Fatores de Risco , /isolamento & purificação
2.
Radiology ; 298(2): E70-E80, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33320063

RESUMO

Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown. Purpose To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data. Materials and Methods A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020. These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis. The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve. Results Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis. The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I2 = 0.93) and 14.8% (95% CI: 8.5, 24.5; I2 = 0.94), respectively. PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography. DVT was present in 42.4% of patients with PE. D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 µg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively). Conclusion Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT. The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19. © RSNA, 2020 Supplemental material is available for this article. See also the editorial by Woodard in this issue.


Assuntos
/complicações , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Trombose Venosa/complicações , Trombose Venosa/diagnóstico por imagem , /sangue , Angiografia por Tomografia Computadorizada/métodos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Embolia Pulmonar/sangue , Trombose Venosa/sangue
3.
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
4.
J. negat. no posit. results ; 5(12): 1516-1527, dic. 2020. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-195998

RESUMO

INTRODUCTION: It has been determined that patients with SARS-CoV-2 infection and severe pneumonia with elevated D-dimer values ​​can develop acute pulmonary thromboembolism (APE) as a complication, being one of the causes related to mortality in this group of patients. METHODS: A retrospective analysis of 12 patients diagnosed with SARS-CoV-2 infection with high clinical suspicion of APE confirmed by computed tomography pulmonary angiopgraphy (CTPA) was performed and the described findings are described. RESULTS: 12 patients with diagnosis of severe pneumonia, elevated D-dimer 9.2 μg / ml (1.4 - ˃20 μg / mL) and confirmation of SARS-CoV-2 infection through real-time reverse transcription polymerasa chain reaction (RT-PCR). APEs were observed mainly in segmental arteries (75%) and main arteries (25%). Pneumonia with patched areas of bilateral ground glass opacities was observed in 100% of the sample as a typical finding of SARS-CoV-2 infection. CONCLUSION: SARS-CoV-2 infection is related to elevation of D-dimer and APE. The CTPA determines the diagnosis, severity and timely management (anticoagulation) of patients with APE. Therefore CTPA should be considered in all patients with elevated D-dimer or clinical worsening


INTRODUCCIÓN: Se ha determinado que los pacientes con infección por SARS-CoV-2 y neumonía severa con valores elevados de dímero-D, pueden desarrollar tromboembolismo pulmonar agudo (TEP) como complicación, siendo una de las causas relacionada con la mortalidad en este grupo de pacientes. MATERIAL Y MÉTODOS: Se realizó un análisis retrospectivo de 12 pacientes con diagnóstico de infección por SARS-CoV-2 con alta sospecha clínica de APE confirmado por angio tomografia computarizada (AngioTC) y se describen los hallazgos descritos. RESULTADOS: 12 pacientes con diagnóstico de neumonía severa, dímero-D elevado 9,2 μg/ml (1,4 - ˃20 μg/ml) y confirmación de infección de SARS-CoV-2 a través de reacción en cadena de polimerasa reversa (RT-PCR). Se objetivaron TEP principalmente en arterias segmentarias (75%) y arterias principales (25%). En el 100% de la muestra se objetivó neumonía con áreas parcheadas de vidrio deslustrado bilaterales como hallazgo típico de infección por SARS-CoV-2. CONCLUSIÓN: La infección por SARS-CoV-2 está relacionada con elevación del dímero-D y con TEP. La angioTC determina el diagnóstico, severidad y manejo oportuno (anticoagulación) de los pacientes con TEP. Por tanto el angioTC debe ser considerado en todos los pacientes con dímero-D elevado o empeoramiento clínico


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Pandemias , Embolia Pulmonar/sangue , Embolia Pulmonar/virologia , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Índice de Gravidade de Doença , Embolia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Doença Aguda
5.
PLoS One ; 15(12): e0243533, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370304

RESUMO

BACKGROUND: A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE. METHODS: This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients. RESULTS: Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p = 0.004); week 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p = 0.003); and week 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively. CONCLUSIONS: Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.


Assuntos
/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/administração & dosagem , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Idoso , Angiografia por Tomografia Computadorizada , Feminino , Testes Hematológicos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
6.
Emerg Radiol ; 27(6): 679-689, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33025219

RESUMO

PURPOSE: COVID-19 raises D-dimer (DD) levels even in the absence of pulmonary embolism (PE), resulting in an increase in computed tomography pulmonary angiogram (CTPA) requests. Our purpose is to determine whether there are differences between DD values in PE-positive and PE-negative COVID-19 patients and, if so, to establish a new cutoff value which accurately determines when a CTPA is needed. METHODS: This study retrospectively analyzed all COVID-19 patients who underwent a CTPA due to suspected PE between March 1 and April 30, 2020, at Ramón y Cajal University Hospital, Madrid (Spain). DD level comparisons between PE-positive and PE-negative groups were made using Student's t test. The optimal DD cutoff value to predict PE risk in COVID-19 patients was calculated in the ROC curve. RESULTS: Two hundred forty-two patients were included in the study. One hundred fifty-one (62%) were men and the median age was 68 years (IQR 55-78). An increase of DD (median 3260; IQR 1203-9625 ng/mL) was detected in 205/242 (96%) patients. 73/242 (30%) of the patients were diagnosed with PE on CTPA. The DD median value was significantly higher (p < .001) in the PE-positive group (7872, IQR 3150-22,494 ng/mL) compared with the PE-negative group (2009, IQR 5675-15,705 ng/mL). The optimal cutoff value for DD to predict PE was 2903 ng/mL (AUC was 0.76 [CI 95% 0.69-0.83], sensitivity 81%). The overall mortality rate was 16% (39/242). CONCLUSION: A higher threshold (2903 ng/mL) for D-dimer could predict the risk of PE in COVID-19 patients with a sensitivity of 81%.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Infecções por Coronavirus/epidemiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Pneumonia Viral/epidemiologia , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Espanha/epidemiologia
7.
Anesth Analg ; 131(5): 1324-1333, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33079850

RESUMO

Patients with coronavirus disease 2019 (COVID-19) frequently experience a coagulopathy associated with a high incidence of thrombotic events leading to poor outcomes. Here, biomarkers of coagulation (such as D-dimer, fibrinogen, platelet count), inflammation (such as interleukin-6), and immunity (such as lymphocyte count) as well as clinical scoring systems (such as sequential organ failure assessment [SOFA], International Society on Thrombosis and Hemostasis disseminated intravascular coagulation [ISTH DIC], and sepsis-induced coagulopathy [SIC] score) can be helpful in predicting clinical course, need for hospital resources (such as intensive care unit [ICU] beds, intubation and ventilator therapy, and extracorporeal membrane oxygenation [ECMO]) and patient's outcome in patients with COVID-19. However, therapeutic options are actually limited to unspecific supportive therapy. Whether viscoelastic testing can provide additional value in predicting clinical course, need for hospital resources and patient's outcome or in guiding anticoagulation in COVID-19-associated coagulopathy is still incompletely understood and currently under investigation (eg, in the rotational thromboelastometry analysis and standard coagulation tests in hospitalized patients with COVID-19 [ROHOCO] study). This article summarizes what we know already about COVID-19-associated coagulopathy and-perhaps even more importantly-characterizes important knowledge gaps.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/terapia , Inflamação/terapia , Pneumonia Viral/terapia , Embolia Pulmonar/terapia , Tromboembolia Venosa/terapia , Trombose Venosa/terapia , Anti-Inflamatórios/efeitos adversos , Anticoagulantes/efeitos adversos , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Medicina Baseada em Evidências , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Mortalidade Hospitalar , Interações Hospedeiro-Patógeno , Humanos , Inflamação/sangue , Inflamação/mortalidade , Inflamação/virologia , Mediadores da Inflamação/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Embolia Pulmonar/sangue , Embolia Pulmonar/mortalidade , Embolia Pulmonar/virologia , Fatores de Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/virologia , Trombose Venosa/sangue , Trombose Venosa/mortalidade , Trombose Venosa/virologia
10.
Arterioscler Thromb Vasc Biol ; 40(10): 2360-2375, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32787516

RESUMO

OBJECTIVE: Platelet activation by stimulatory factors leads to an increase in intracellular calcium concentration ([Ca2+]i), which is essential for almost all platelet functions. Modulation of Ca2+ influx and [Ca2+]i in platelets has been emerging as a possible strategy for preventing and treating platelet-dependent thrombosis. Voltage-gated potassium 1.3 channels (Kv1.3) are highly expressed in platelets and able to regulate agonist-evoked [Ca2+]i increase. However, the role of Kv1.3 channels in regulating platelet functions and thrombosis has not yet been elucidated. In addition, it is difficult to obtain a specific blocker for this channel, since Kv1.3 shares identical drug-binding sites with other K+ channels. Here, we investigate whether specific blockade of Kv1.3 channels by monoclonal antibodies affects platelet functions and thrombosis. Approach and Results: In this study, we produced the anti-Kv1.3 monoclonal antibody 6E12#15, which could specifically recognize both human and mouse Kv1.3 proteins and sufficiently block Kv1.3 channel currents. We found Kv1.3 blockade by 6E12#15 inhibited platelet aggregation, adhesion, and activation upon agonist stimulation. In vivo treatment with 6E12#15 alleviated thrombus formation in a mesenteric arteriole thrombosis mouse model and protected mice from collagen/epinephrine-induced pulmonary thromboembolism. Furthermore, we observed Kv1.3 regulated platelet functions by modulating Ca2+ influx and [Ca2+]i elevation, and that this is mediated in part by P2X1. Interestingly, Kv1.3-/- mice showed impaired platelet aggregation while displayed no abnormalities in in vivo thrombus formation. This phenomenon was related to more megakaryocytes and platelets produced in Kv1.3-/- mice compared with wild-type mice. CONCLUSIONS: We showed specific inhibition of Kv1.3 by the novel monoclonal antibody 6E12#15 suppressed platelet functions and platelet-dependent thrombosis through modulating platelet [Ca2+]i elevation. These results indicate that Kv1.3 could act as a promising therapeutic target for antiplatelet therapies.


Assuntos
Anticorpos Monoclonais/farmacologia , Plaquetas/efeitos dos fármacos , Fibrinolíticos/farmacologia , Canal de Potássio Kv1.3/antagonistas & inibidores , Inibidores da Agregação de Plaquetas/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Embolia Pulmonar/prevenção & controle , Trombose/prevenção & controle , Animais , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/metabolismo , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Canal de Potássio Kv1.3/sangue , Canal de Potássio Kv1.3/deficiência , Canal de Potássio Kv1.3/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ativação Plaquetária/efeitos dos fármacos , Embolia Pulmonar/sangue , Embolia Pulmonar/genética , Embolia Pulmonar/metabolismo , Transdução de Sinais , Trombose/sangue , Trombose/genética , Trombose/metabolismo
11.
Arterioscler Thromb Vasc Biol ; 40(10): 2527-2538, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32757649

RESUMO

OBJECTIVE: Deep vein thrombosis and pulmonary embolism referred as venous thromboembolism (VTE) are a common cause of morbidity and mortality. Plasma from healthy controls or individuals who have experienced a VTE were analyzed using metabolomics to characterize biomarkers and metabolic systems of patients with VTE. Approach and Results: Polar metabolite and lipidomic profiles from plasma collected 3 months after an incident VTE were obtained using liquid chromatography mass spectrometry. Fasting-state plasma samples from 42 patients with VTE and 42 healthy controls were measured. Plasma metabolomic profiling identified 512 metabolites forming 62 biological clusters. Multivariate analysis revealed a panel of 21 metabolites altogether capable of predicting VTE status with an area under the curve of 0.92 (P=0.00174, selectivity=0.857, sensitivity=0.971). Multiblock systems analysis revealed 25 of the 62 functional biological groups as significantly affected in the VTE group (P<0.05 to control). Complementary correlation network analysis of the dysregulated functions highlighted a subset of the lipidome composed mainly of n-3 long-chain polyunsaturated fatty acids within the predominant triglycerides as a potential regulator of the post-VTE event biological response, possibly controlling oxidative and inflammatory defence systems, and metabolic disorder associated dysregulations. Of interest was microbiota metabolites including trimethylamine N-oxide that remained associated to post incident VTE patients, highlighting a possible involvement of gut microbiota on VTE risk and relapse. CONCLUSIONS: These findings show promise for the elucidation of underlying mechanisms and the design of a diagnostic test to assess the likely efficacy of clinical care in patients with VTE.


Assuntos
Metabolismo Energético , Lipídeos/sangue , Metabolômica , Embolia Pulmonar/sangue , Biologia de Sistemas , Tromboembolia Venosa/sangue , Trombose Venosa/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Microbioma Gastrointestinal , Humanos , Incidência , Lipidômica , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/epidemiologia , Recidiva , Fatores de Tempo , Tromboembolia Venosa/diagnóstico por imagem , Tromboembolia Venosa/epidemiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/epidemiologia
12.
Vascul Pharmacol ; 133-134: 106783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32835836

RESUMO

BACKGROUND: Low-molecular-weight heparins (LMWHs) influence the fibrin network structure in in vitro models. There have been no reports on LMWH-induced modifications of fibrin clot characteristics and their determinants in acute pulmonary embolism (PE). AIM: We investigated how enoxaparin alters fibrin clot properties in acute PE patients. METHODS: Clots were generated from plasma of 46 acute PE patients, aged 47-77 years treated with enoxaparin 1 mg/kg bid. Fibrin clot permeability (Ks) and clot lysis time (CLT), along with coagulation and fibrinolysis proteins were determined. Plasma fibrin clot nanostructure was assessed using scanning electron microscopy (SEM). RESULTS: Both Ks and CLT were associated with anti-factor (F)Xa activity (r = 0.75, p < 0.0001 and r = -0.37, p = 0.011). Anti-FXa was positively associated with fibrin fiber diameter and the pore area, and inversely with fibrin fiber density on SEM images. Multiple regression analysis adjusted for age, body-mass index, and fibrinogen levels showed that anti-FXa activity, antithrombin activity, and FVIII activity determined Ks, while anti-FXa activity, plasminogen activator inhibitor-1 level, and presence of right ventricular dysfunction determined CLT. CONCLUSIONS: We identified new laboratory and clinical factors contributing to prothrombotic plasma fibrin clot characteristics during enoxaparin treatment, which might help elucidate mechanisms underlying therapy failure in patients with acute PE.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Enoxaparina/uso terapêutico , Fibrina/metabolismo , Fibrinolíticos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Adulto , Idoso , Feminino , Fibrina/ultraestrutura , Tempo de Lise do Coágulo de Fibrina , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Porosidade , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Falha de Tratamento
13.
Emergencias ; 32(4): 253-257, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32692002

RESUMO

OBJECTIVES: To analyze clinical, laboratory, and radiologic findings and final health outcomes in patients with pulmonary embolism and coronavirus disease 2019 (COVID-19). To compare them to findings and outcomes in patients with pulmonary embolism without COVID-19. MATERIAL AND METHODS: Multicenter, observational, retrospective study in 4 Spanish hospital emergency departments (EDs) from January 15 to April 15, 2020. Cases were located by reviewing all ED requests for pulmonary computed tomography angiography (CTA) procedures. Clinical, laboratory, and radiologic findings; medical histories and comorbidity; risk factors; and outcomes were compared between the 2 groups of patients (with or without COVID-19). RESULTS: A total of 399 CTAs were ordered; 88 pulmonary embolisms were diagnosed, 28 of them (32%) in patients with COVID-19. This group had more men, and a history of thromboembolic disease was more common. We found no between-group differences in clinical presentation, laboratory, or radiologic findings; nor were there differences in final outcomes. In-hospital mortality was 7% (2 cases) in patients with COVID-19 and 17% (10 cases) in patients without the virus (odds ratio for death in patients with pulmonary embolism and COVID-19, 0.38; 95% CI, 0.08-1.89). CONCLUSION: We found no clinically important differences in the clinical, laboratory, or radiologic findings between patients with or without COVID-19 who were treated for pulmonary embolism in our hospital EDs. Final outcomes also did not differ.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/diagnóstico por imagem , Idoso , Comorbidade , Angiografia por Tomografia Computadorizada/estatística & dados numéricos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal , Tempo de Internação , Masculino , Razão de Chances , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Embolia Pulmonar/sangue , Embolia Pulmonar/etiologia , Embolia Pulmonar/mortalidade , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia
14.
Chest ; 158(5): 2130-2135, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32710891
15.
Clin Appl Thromb Hemost ; 26: 1076029620936772, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726134

RESUMO

The aim of this study was to describe clinical, imaging, and laboratory features of acute pulmonary embolism (APE) in patients with COVID-19 associated pneumonia. Patients with COVID-19 associated pneumonia who underwent a computed tomography pulmonary artery (CTPA) scan for suspected APE were retrospectively studied. Laboratory data and CTPA images were collected. Imaging characteristics were analyzed descriptively. Laboratory data were analyzed and compared between patients with and without APE. A series of 25 COVID-19 patients who underwent CTPA between January 2020 and February 2020 were enrolled. The median D-dimer level founded in these 25 patients was 6.06 µg/mL (interquartile range [IQR] 1.90-14.31 µg/mL). Ten (40%) patients with APE had a significantly higher level of D-dimer (median, 11.07 µg/mL; IQR, 7.12-21.66 vs median, 2.44 µg/mL; IQR, 1.68-8.34, respectively, P = .003), compared with the 15 (60%) patients without APE. No significant differences in other laboratory data were found between patients with and without APE. Among the 10 patients with APE, 6 (60%) had a bilateral pulmonary embolism, while 4 had a unilateral embolism. The thrombus-prone sites were the right lower lobe (70%), the left upper lobe (60%), both upper lobe (40%) and the right middle lobe (20%). The thrombus was partially or completely absorbed after anticoagulant therapy in 3 patients who underwent a follow-up CTPA. Patients with COVID-19 associated pneumonia have a risk of developing APE during the disease. When the D-dimer level abnormally increases in patients with COVID-19 pneumonia, CTPA should be performed to detect and assess the severity of APE.


Assuntos
Betacoronavirus , Angiografia por Tomografia Computadorizada/métodos , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Doença Aguda , Adulto , Idoso , Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Artéria Pulmonar/anatomia & histologia , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/virologia , Embolia Pulmonar/sangue , Embolia Pulmonar/etiologia , Embolia Pulmonar/virologia , Estudos Retrospectivos , Trombose/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos
16.
Thromb Res ; 195: 95-99, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32682004

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer. Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19. OBJECTIVES: To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE. We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19. PATIENTS/METHODS: Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR). RESULTS: There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care. The diagnostic yield for PE was 37%. The overall proportion of PE in patients with COVID-19 was 5.4%. The proportions with Wells score of ≥4 ('PE likely') was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951). The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3-9) in PE group vs 4 (IQR 2-7) in those without PE (P = 0.133). D-dimer was higher in PE (median 8000 ng/mL; IQR 4665-8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210-4410 ng/mL, P < 0.001). In the 'low probability' group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE. CONCLUSIONS: Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common. Of note, approaching half of PE events were diagnosed on hospital admission. More data are needed to identify an optimal diagnostic pathway in patients with COVID-19. Randomised controlled trials of intensified thromboprophylaxis are urgently needed.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/etiologia , Betacoronavirus/isolamento & purificação , Coagulação Sanguínea , Angiografia por Tomografia Computadorizada , Infecções por Coronavirus/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos
17.
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
18.
J Thromb Thrombolysis ; 50(3): 558-566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32617807

RESUMO

COVID-19 is associated with a variety of clinical complications including coagulopathy, which frequently results in venous thromboembolism (VTE). Retrospective analyses reported a markedly increased rate of VTEs in COVID-19. However, most recent studies on coagulopathy in COVID-19 were only focused on critically ill patients, and without suitable control groups. We aimed to evaluate the rate of VTEs in an all-comers cohort with suspected COVID-19 during a 30-days follow-up period. We also studied the level of D-dimers and their association with the course of disease. In our prospective single-center study (DRKS00021206, 03/30/2020), we analyzed 190 patients with suspected COVID-19 admitted to the emergency department between March and April 2020. Forty-nine patients were SARS-CoV-2 positive (25.8%). The 141 SARS-CoV-2-negative patients served as control group. After completion of a 30-days follow-up, VTE was diagnosed in 3 patients of the SARS-CoV-2-positive group (6.1%, amongst these 2 ICU cases) versus 5 patients in the SARS-CoV-2-negative group (3.5%), however the difference was not statistically significant (p = 0.427). 30-days mortality was similar in both groups (6.1% vs. 5%, p = 0.720). Disease severity correlated with the maximum level of D-dimers during follow-up in COVID-19. The rate of VTE was numerically higher in SARS-CoV-2 positive all-comers presenting with suspected COVID-19 as compared to well-matched controls suffering from similar symptoms. VTEs in the COVID-19 group predominantly occurred in ICU courses. The maximum level of D-dimers during follow-up was associated with disease severity in COVID-19, whereas the level of D-dimers at admission was not.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Alemanha/epidemiologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Estudos Prospectivos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/virologia , Sistema de Registros , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/virologia , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/virologia
19.
J Vasc Interv Radiol ; 31(8): 1281-1289, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32703545

RESUMO

PURPOSE: To evaluate the effect of catheter-directed thrombolysis (CDT) with tissue plasminogen activator (tPA) on plasma fibrinogen levels (PFLs) in the setting of acute pulmonary embolism (PE) and the relationship between PFL and hemorrhagic complications. MATERIALS AND METHODS: A retrospective review of CDT procedures between 2009 and 2019 identified 147 CDT procedures for massive or submassive PE (55.8% males; age, 56.5 ± 14.8 years; 90.5% submassive). All patients received therapeutic anticoagulation during CDT with unfractionated heparin (UFH) (69.4%) or low-molecular-weight heparin (LMWH, 30.6%) infusion. CDT was performed with ultrasound-accelerated thrombolysis (USAT) catheters (n = 98), conventional catheter-directed thrombolysis (CCDT) catheters (n = 34), or a combination of both (n = 15). RESULTS: There was a decrease (P = .007) of 15.1 ± 69.4 mg/dl from the initial PFL (376.1 ± 122.7 mg/dl) to the final PFL (361 ± 118.7 mg/dl), which was measured after a mean of 24.1 ± 11.7 hours with a mean tPA dose of 28.3 ± 14.2 mg. The fibrinogen nadir was 327.6 ± 107.1 mg/dl measured 13.4 ± 10.3 hours after initiation of thrombolysis. Of patients with hemorrhagic complications (n = 6), initial, final, and nadir PFL were not significantly lower (P = .053, P = .081, and P = .086, respectively) than the remainder of the cohort. No significant difference was noted in initial and final PFL between the LMWH and UFH groups (P = .2 and P = .1, respectively) or between the CCDT and USAT groups (P = .5 and P = .9, respectively). The UFH group had a lower nadir PFL than the LMWH group (P = .03). CONCLUSIONS: Despite a significant drop in PFL during CDT for acute PE, this was not associated with hemorrhagic complications. These findings were not affected by the choice of anticoagulant or catheter delivery system.


Assuntos
Fibrinogênio/metabolismo , Fibrinolíticos/administração & dosagem , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Doença Aguda , Adulto , Idoso , Anticoagulantes/administração & dosagem , Biomarcadores/sangue , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/sangue , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
20.
Eur J Clin Invest ; 50(7): e13311, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32511751
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