ABSTRACT Exacerbated inflammation and coagulation are a hallmark of COVID-19 severity. Extracellular vesicles (EVs) are intercellular transmitters involved in inflammatory conditions, which are capable of triggering prothrombotic mechanisms. Since the release of EVs is potentially associated with COVID-19-induced coagulopathy, the aim of this study was to evaluate changes in inflammation- and hypercoagulability-related EVs during the first month after symptom onset and to determine whether they are associated with disease severity. Blood samples of patients with mild or severe forms of the disease were collected on three occasions: in the second, third and fourth weeks after symptom onset for the quantification by flow cytometry of CD41A (platelet glycoprotein IIb/IIIa), CD162 (PSGL-1), CD31 (PECAM-1) and CD142 cells (tissue factor). Analysis of variance (ANOVA) with repeated measures, Kruskal-Wallis and correlation tests were used. Eighty-five patients were enrolled, 71% of whom had mild disease. Seventeen uninfected individuals served as controls. Compared to controls, both mild and severe COVID-19 were associated with higher EV-CD31+, EV-CD41+ and EV-CD142+ levels. All EV levels were higher in severe than in mild COVID-19 only after the third week from symptom onset, as opposed to C-reactive protein and D-dimer levels, which were higher in severe than in mild COVID-19 earlier during disease progression. EV levels were also associated with C-reactive protein and D-dimer levels only after the third week of symptoms. In conclusion, EVs expressing CD41A, CD31, TF, and CD162 appear as late markers of COVID-19 severity. This finding may contribute to the understanding of the pathogenesis of acute and possibly long COVID-19. COVID19 COVID 19 COVID-1 severity (EVs conditions mechanisms COVID19induced COVIDinduced induced coagulopathy hypercoagulabilityrelated hypercoagulability related occasions second CDA CD A platelet IIb/IIIa, IIbIIIa IIb/IIIa , IIb IIIa IIb/IIIa) CD16 PSGL1, PSGL1 PSGL 1 (PSGL-1) CD3 PECAM1 PECAM (PECAM-1 CD14 tissue factor. factor . factor) ANOVA (ANOVA measures KruskalWallis Kruskal Wallis used Eightyfive Eighty five enrolled 71 controls EVCD31+, EVCD31 EVCD CD31+, EV-CD31+ EVCD41+ EVCD41 CD41+ CD41 EV-CD41 EVCD142+ EVCD142 CD142+ EV-CD142 Creactive C reactive Ddimer D dimer progression symptoms conclusion TF COVID19. 19. COVID1 COVID- CD1 (PSGL-1 (PECAM- 7 EVCD31+ EVCD3 CD31+ EV-CD31 EVCD4 CD4 EV-CD4 EVCD14 EV-CD14 (PSGL- (PECAM EV-CD3 EV-CD EVCD1 EV-CD1 (PSGL

OBJETIVO: O valproato de sódio é um fármaco anticonvulsivante usado com frequência no manejo dos quadros epilépticos refratários na infância e habitualmente apresenta boas taxas de resposta e toxicidade aceitável. O objetivo deste artigo é destacar os efeitos colaterais secundários ao uso prolongado de valproato de sódio em uma criança e alertar para a importância do acompanhamento dos pacientes em uso crônico de anticonvulsivantes. DESCRIÇÃO DO CASO: Criança do sexo masculino, com quatro anos e oito meses, portadora de síndrome de West, em uso de valproato de sódio desde os seis meses de idade, admitida no hospital com anemia, macrocitose, plaquetopenia, deficiência de vitamina B12, hipoalbuminemia e hiponatremia. Durante a internação e o acompanhamento ambulatorial, relacionou-se o quadro clínico ao uso do valproato de sódio. COMENTÁRIOS: A toxicidade hematológica do valproato de sódio é bem conhecida e comum, podendo variar em relação à época de instalação e gravidade. Os achados mais frequentes são a plaquetopenia e a macrocitose. Além das alterações hematológicas, a literatura relata outros efeitos colaterais relacionados ao uso do fármaco. Destaca-se a importância do conhecimento e monitorização dos eventos adversos nos pacientes submetidos a esse tipo de terapia, para que eles possam ser detectados e tratados o mais precocemente.

OBJECTIVE: Valproic acid is an anticonvulsant frequently used in the management of childhood refractory epilepsy with good clinical responses and acceptable toxicity. The objective of this case report is to describe side effects associated with long-term valproate therapy in a child and to warn about the importance of monitoring patients in chronic use of anticonvulsants. CASE DESCRIPTION: This male child, four years and eight months old, with West syndrome, had been using sodium valproate since six months of age. The patient was admitted with anemia, macrocytosis, thrombocytopenia, deficiency of vitamin B12, hypoalbuminemia and hyponatremia. The clinical signs were associated to chronic sodium valproate use. COMMENTS: Sodium valproate hematologic toxicity is frequent, varying in onset and severity. The most common findings are thrombocytopenia and macrocytosis. In addition to the hematological toxicity, literature reports other side effects associated with valproic acid therapy. It is important to know and to monitor adverse effects in patients undergoing sodium valproate therapy in order to detect and treat them as early as possible.