RESUMO
Pulmonary embolism (PE) is a commonly encountered clinical entity in patients with coronavirus disease 2019 (COVID-19). Up to 1/3 of patients have been found to have PE in the setting of COVID-19. Given the novelty of the virus causing this pandemic, it has not been easy to address diagnostic and management issues in PE. Ongoing research and publications of the scientific literature have helped in dealing with COVID-19 lately and this applies to PE as well. In this article, we attempt to succinctly yet comprehensively discuss PE in patients with COVID-19 with a review of the prevailing literature.
Assuntos
COVID-19/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Trombofilia/sangue , Anticoagulantes/uso terapêutico , COVID-19/complicações , Angiografia por Tomografia Computadorizada , Gerenciamento Clínico , Coagulação Intravascular Disseminada/sangue , Ecocardiografia , Oxigenação por Membrana Extracorpórea , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Extremidade Inferior/diagnóstico por imagem , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Sistemas Automatizados de Assistência Junto ao Leito , Tempo de Protrombina , Embolia Pulmonar/sangue , Embolia Pulmonar/etiologia , Terapia Trombolítica , Trombofilia/complicações , Ultrassonografia Doppler Dupla , Trombose Venosa/diagnóstico por imagem , Cintilografia de Ventilação/PerfusãoRESUMO
The formation of a thrombus is a key event in thromboembolic disorders, that contribute to high mortality and morbidity in affected patients. In the present study, we synthesized a library of novel substituted 3,3-dibutyl-8-methoxy-2,3-dihydrobenzo [b] [1,4] thiazepin-4(5H)-one derivatives which were tested for their platelet aggregation and thrombin inhibitory activity. Among the tested compounds, 3,3-dibutyl-7-(2-chlorophenyl)-8-methoxy-2,3-dihydrobenzo[b] [1,4]thiazepin-4(5H)-one (DCT) displayed the maximum thrombin inhibition with an IC50 value of 3.85⯵M and thus DCT was chosen for further studies. Next, the effect of DCT on primary hemostasis was evaluated using agonist-induced platelet aggregation model. The lead compound inhibited the collagen- or ADP- or thrombin-induced platelet aggregation in a dose-dependent manner. Furthermore, DCT prolonged the process of clot formation when evaluating plasma re-calcification time (320⯱â¯11â¯sec at 5⯵g DCT), activated partial thromboplastin time (58.0⯱â¯0.01â¯sec at 2⯵g), and prothrombin time (14.7⯱â¯0.01â¯sec at 5⯵g). Molecular docking studies suggested that the benzothiazepinones evaluated here consistently display hydrogen bonding with Ser214 of thrombin, which is similar to that of the co-crystallized ligand (1-(2R)-2-amino-3-phenyl-propanoyl-N-(2,5dichlorophenyl)methylpyrrolidine-2-carboxamide). DCT displayed additional hydrogen bonding to Ser195 and π-π interactions between its methoxyphenyl groups and Trp60, thereby providing a structural rationale for the observed biological effect.
Assuntos
Inibidores de Serina Proteinase/farmacologia , Tiazepinas/farmacologia , Trombina/antagonistas & inibidores , Relação Dose-Resposta a Droga , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Serina Proteinase/síntese química , Inibidores de Serina Proteinase/química , Relação Estrutura-Atividade , Tiazepinas/síntese química , Tiazepinas/química , Trombina/metabolismoRESUMO
Pulmonary embolism (PE) is a serious medical condition that can occur as a result of venous thromboembolism (VTE). COVID-19, also known as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), can potentially lead to PE due to the formation of blood clots in the lungs. This study aims to collate and report trends of PE in patients with long COVID (4-12 weeks since infection) and post-COVID-19 syndrome (>12 weeks since infection). The study adhered to PRISMA Statement 2020 guidelines, and a systematic search was conducted in four databases. In total, nine observational studies were included with a total patient count of 45,825,187. The incidence of PE with long COVID/post-COVID-19 syndrome was seen among 31,885 individuals out of 44,967,887 participants. The incidence rate of PE was observed as 0.07%, given that the studies included matched controls. While we cannot state with certainty that COVID-19 infection in itself leads to higher risks of PE at a later time, this study emphasizes the need for optimized care and longitudinal studies during the COVID-19 era to account for deviations from the norm.