Evaluation of Clotting Factors in Hospitalized Critically-Ill Individuals with Suspected Covid-19

Aims: The Coronavirus Disease 2019 (COVID-19), that results of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, manifests with dysfunction of hemostasis and thrombosis. This study aims to evaluate laboratory parameters of hemostasis in hospitalized individuals with suspected COVID-19. Method(s): Individuals aged 18 years or older with suspected COVID-19 admitted to two hospitals were invited to participate in this study. The study inclusion period was from April 2020 to March 2021. The study was approved by the institutional ethics committees. The diagnosis of COVID-19 was confirmed by positive SARS-CoV-2 real-time reverse-transcription polymerase chain reaction. Antithrombin, factor V, factor VII, factor XI, factor XII, factor XIII and prothrombin assays were performed using the Multiplex immunoassay technique (ThermoFisher Scientific, Vienna, Austria). Propensity score matching for sex and age were estimated by a logistic regression model for COVID-19 and non-COVID-19 individuals in the R software. The proportions found in each group were compared by Fisher's exact test, when the variable was categorical, and by the Mann-Whitney test, when it was continuous. Linear regression was performed adjusting the levels of clotting factors and antithrombin for the severity score (Sequential Organ Failure Assessment - SOFA). Correlation between SOFA, clotting factors and antithrombin in individuals with COVID-19 were performed by using the Spearman test. Only very strong correlations (>=0.9) were considered;p-value<0.05 was considered statistically significant. Result(s): A total of 151 individuals were included in the study, of whom 138 (91.4%) with the diagnosis of COVID-19 and 13 (8.6%) non-COVID-19. After 2:1 matching, 26 individuals with COVID-19 and 13 non-COVID-19 participated in the study. In the univariate analysis, the group of COVID-19 had higher levels of antithrombin, factor V, factor VII, factor XI and prothrombin compared to the non-COVID-19 group. However, after adjusting for SOFA, only the levels of factor XI and prothrombin remained different between the groups (higher in the COVID-19) (p=0.04 and p=0.04, respectively). We found no association between factor XI and prothrombin with mortality. However, we found a very strong correlation between coagulation factors V and VII (r=0.923, p<0.0001). Discussion(s): Our results show that plasma levels of antithrombin, factor V, factor VII, factor XI and prothrombin were higher in the COVID-19 when compared with non-COVID-19 group of critically-ill patients, but the difference was lost after adjusting the analysis for SOFA. Only the levels of factor XI and prothrombin remained significant in the COVID-19 group after adjustment. This finding suggests that the severity of the disease rather than viral etiology was the main determinant of the difference in the plasma levels of these proteins. We also showed a strong correlation between factor V and VII in our study. Indeed, factor VII is the major trigger of coagulation in vivo. Therefore, it is possible that factor V and VII could act together to boost coagulation and promote thrombus formation in patients with COVID-19. Conclusion(s): Our study suggests that increased levels of procoagulant factors in hospitalized critically-ill individuals with suspected COVID-19 are rather related to disease severity than to its cause. Copyright © 2022

INCIDÊNCIA DE EVENTOS TROMBÓTICOS EM INDIVÍDUOS HOSPITALIZADOS POR COVID-19 EM BELO HORIZONTE

Objetivo: Avaliar incidência de eventos trombóticos em indivíduos hospitalizados por Coronavirus Disease 2019 (COVID-19). Material e métodos: Foram avaliados indivíduos de ambos os gêneros com idade ≥ 18 anos internados por complicações da COVID-19 em dois hospitais de Belo Horizonte, Minas Gerais, entre abril de 2020 e março de 2021. Todos os participantes apresentaram um resultado positivo de real-time reverse-transcription polymerase chain reaction (RT-PCR) para severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A inclusão no estudo foi feita mediante assinatura de termo de consentimento lido e esclarecido que foi oferecido aos participantes potencialmente elegíveis ou seu responsável legal. Foi realizado duplex scan venoso em membros inferiores em todos os indivíduos à admissão do estudo, no terceiro e no sétimo dias de internação hospitalar, além na suspeita de trombose venosa profunda quando a mesma não ocorreu nesses dias estabelecidos. Na suspeita clínica de tromboembolismo pulmonar ou acidente vascular encefálico, foram realizadas angiotomografia arterial de tórax e tomografia computadorizada de crânio, respectivamente. Os dados coletados foram tabulados para análise por intermédio do programa Research electronic data Capture – RedCap. As variáveis numéricas foram descritas como mediana e intervalo interquartil, conforme distribuição não normal, avaliada em teste de Shapiro-Wilk. As variáveis categóricas foram expressas em frequência e percentual. Para a realização das análises, o software SPSS 22.0 foi utilizado. O estudo foi aprovado pelo comitê de ética institucional. Resultados: Foram inclusos 151 indivíduos com suspeita de COVID-19. Houve exclusão de 13 indivíduos pelo fato de apresentarem RT-PCR negativo para SARS-CoV-2 e de dois, por falta de dados necessários para a análise. 66,7% dos indivíduos avaliados eram do sexo masculino, com mediana de idade de 63 anos (intervalo interquartil 51 – 72). 80,8% necessitaram de internação em centro de tratamento intensivo e 86,8% possuíam comorbidades. 38,4% dos indivíduos evoluíram para óbito durante internação hospitalar. Foram identificados nove eventos trombóticos nos indivíduos participantes: cinco tiveram trombose venosa profunda em membros inferiores, dois apresentaram trombose pulmonar e dois com acidente vascular cerebral isquêmico. A incidência de eventos trombóticos global encontrada nessa coorte foi de 6,6%, sendo 5,1% de casos venosos e 1,5% de ocorrências arteriais. Discussão: A COVID-19 é relacionada à maior ocorrência de eventos trombóticos, com incidência variando pela gravidade da doença e pela diferença de populações analisadas. Estudos demonstram que há grande ocorrência de eventos trombóticos, principalmente venosos, de maneira assintomática. A incidência encontrada neste estudo é semelhante à literatura atual. Conclusão: Tromboprofilaxia injetável é uma importante medida para prevenção de complicações relacionações à COVID-19 em pacientes hospitalizados, principalmente, quando associada a protocolos bem estabelecidos de rastreamento de tromboembolismo venoso.

Development of an artificial intelligence model to predict venous thromboembolic disease in COVID-19 patients at hospital admission

Background: A lot of attention has been drawn to the identification of predictors of VTE in COVID-19 patients, and an accurate clinical prediction model is still lacking in this context. Aims: To develop a clinical prediction model using artificial intelligence techniques, to predict VTE in COVID-19 patients, using variables easily available upon hospital admission. Methods: This multicenter cohort included consecutive adult patients (≥ 18 years-old) with laboratory-confirmed COVID-19 from 37 Brazilian hospitals from 17 cities, between March and September 2020. Study data were collected from medical records using Research Electronic Data Capture (REDCap) tools. We trained multiple machine learning models on various combinations of structured and non-structured features, calibrated to reflect a probability distribution while predicting the desired clinical outcome. Subsequently, we analyzed the relationship between this model ' s predicted confidence score and the fraction of false negatives in the test sample to devise a splitting point where no false negatives would occur, thus calibrating for sensitivity over specificity. The study was approved by the National Research Ethics Commission waiving off the application of informed consent. Results: The dataset included 6421 patients (median age 61 [P25-75 48-73] years-old, 54.8% men), 4.5% of them developed venous thromboembolic disease. Patient ' s age, sex and comorbidities, as well as their list of household prescription drugs, history of recent surgery and laboratory tests were significant predictors. Given a proper confidence level, our model predicted 100% of the true positive cases while eliminating a significant portion of the true negatives (Figure 1). (Figure Presented) Conclusions: This study suggests that an ensemble of decision rules can effectively predict COVID patients with high risk of VTE. It might be possible to decrease the use of anticoagulants while still treating patients with an appreciable likelihood of thromboembolism.

Venous thromboembolism in patients hospitalized with COVID-19: Results from the Brazilian COVID-19 registry

Background : COVID-19 patients are at increased risk of venous thromboembolism (VTE), and this complication leads to a worse prognosis. However, to diagnose VTE on COVID-19 patients is a challenge to physicians, as the symptoms of pulmonary embolism can often be mistaken for the overlapped viral pneumonia. Herein, there is still little information on VTE incidence and associated risk factors specifically for this population. Aims : To assess the incidence and associated risk factors for VTE in hospitalized COVID-19 patients in Brazilian hospitals. Methods : Retrospective multicenter cohort in 15 Brazilian hospitals. Consecutive adult patients (≥ 18 years-old) with laboratoryconfirmed COVID-19 between March and September 2020 were included. Study data were collected from medical records using Research Electronic Data Capture (REDCap) tools. The study was approved by the National Research Ethics Commission waiving off the application of informed consent. Results : Of 4,021 patients included, 234 (5.8%) had VTE. When comparing VTE and non-VTE groups (Tables 1 and 2), there was no statistical difference in terms of sex and age between groups. The median age was 63 years-old (IQR 51-72 years-old) in VTE group. The most common comorbidities for both groups were hypertension and diabetes. Obesity, chronic pulmonary obstructive disease, previous VTE and recent surgery were more frequent in VTE group. D-dimer, C-reactive protein, lactate dehydrogenase levels and lymphocyte count were higher in the VTE group. Admission to intensive care units (37.6% vs 69.7%;P < 0,001) and in-hospital mortality (19.0% vs 28.3%;P < 0,01) were significantly higher in those who had VTE. Conclusions : Overall, 5.8% of COVID-19 hospitalized patients had VTE. Elevated laboratory values were associated with increased risk of this condition. VTE was associated with higher rates of intensive care admission and in-hospital mortality.