Persistent hypofibrinolysis in severe COVID-19 associated with elevated fibrinolysis inhibitors activity.

Hypercoagulability and reduced fibrinolysis are well-established complications associated with COVID-19. However, the timelines for the onset and resolution of these complications remain unclear. The aim of this study was to evaluate, in a cohort of COVID-19 patients, changes in coagulation and fibrinolytic activity through ROTEM assay at different time points during the initial 30 days following the onset of symptoms in both mild and severe cases. Blood samples were collected at five intervals after symptoms onset: 6-10 days, 11-15 days, 16-20 days, 21-25 days, and 26-30 days. In addition, fibrinogen, plasminogen, PAI-1, and alpha 2-antiplasmin activities were determined. Out of 85 participants, 71% had mild COVID-19. Twenty uninfected individuals were evaluated as controls. ROTEM parameters showed a hypercoagulable state among mild COVID-19 patients beginning in the second week of symptoms onset, with a trend towards reversal after the third week of symptoms. In severe COVID-19 cases, hypercoagulability was observed since the first few days of symptoms, with a tendency towards reversal after the fourth week of symptoms onset. A hypofibrinolytic state was identified in severe COVID-19 patients from early stages and persisted even after 30 days of symptoms. Elevated activity of PAI-1 and alpha 2-antiplasmin was also detected in severe COVID-19 patients. In conclusion, both mild and severe cases of COVID-19 exhibited transient hypercoagulability, reverted by the end of the first month. However, severe COVID-19 cases sustain hypofibrinolysis throughout the course of the disease, which is associated with elevated activity of fibrinolysis inhibitors. Persistent hypofibrinolysis could contribute to long COVID-19 manifestations.

Safety and efficacy of cryoprecipitate-poor plasma as a replacement fluid for therapeutic plasma exchange in thrombotic thrombocytopenic purpura: a single center retrospective evaluation.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by decreased activity of ADAMTS13, resulting in reduced clearance of ultralarge von Willebrand factor (VWF) multimers. Treatment of TTP is therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma (FFP). Cryoprecipitate-poor plasma (CPP) is a plasma product with lower concentrations of large VWF multimers, and similar amounts of ADAMTS13. CPP is regarded as at least as efficacious as FFP in TTP but evidence of additional benefits has not been demonstrated. Furthermore, there are limited data on the frequency of adverse events associated with CPP. MATERIAL AND METHODS: In our center, the choice between CPP and FFP is performed before the 1st TPE session at the physicians' discretion. Here, we retrospectively evaluated the efficacy and safety of CPP based on the number of sessions, volume of plasma exposure, frequency of exacerbations/relapses, and adverse events. RESULTS: Fourteen patients with newly diagnosed TTP were included in this analysis. The proportion of CPP:FFP use was 5:9. There were no significant differences in age, gender, initial hemoglobin, platelet count, LDH, or etiology of TTP between groups. We observed a trend toward a higher number of TPE sessions and higher plasma exposure in CPP, compared to FFP-treated patients. Acute exacerbations were more frequent among patients treated with CPP (OR 26.6; 95%CI 1.01-703.51; P = 0.03). Mild allergic reactions were the most common treatment-related adverse event in both groups. DISCUSSION: Our data suggest that CPP should not be used as 1st line treatment for newly diagnosed TTP patients.

Extracellular vesicles are a late marker of inflammation, hypercoagulability and COVID-19 severity.

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.

Extracellular vesicles are a late marker of inflammation, hypercoagulability and COVID-19 severity

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.

Suicidal ideation in medical inpatients: psychosocial and clinical correlates.

OBJECTIVE: To identify psychosocial and clinical correlates of suicidal ideation in medical inpatients. METHOD: In a cross-sectional study, all adults consecutively admitted to the medical wards of a University Hospital had their names recorded and were randomized and evaluated during the first week of admission. Suicidal ideation was assessed using Item 9 of Patient Health Questionnaire-9. The Beck Depression Inventory, the Beck Anxiety Inventory, the WHO Subjective well-being scale, the Charlson Comorbidity Index and other numerical rating scales (pain and self-reported physical illness severity) were used. Patients with less than four confidants were considered with poor social support. The Student's t test, Mann-Whitney U test, chi-square test and stepwise logistic regression analysis were used. RESULTS: Of the 1092 patients who composed the sample, 7.2% reported having suicidal ideation. After adjusting for psychosocial and clinical confounders, prior suicide attempts (OR: 4.41; 95% CI: 2.12-9.15; P<.001), depressive symptoms (OR: 1.11; 95% CI: 1.06-1.17; P<.001), severe anxiety symptoms (OR: 3.04; 95% CI: 1.47-6.26; P=.003) and poor social support (OR: 2.02; 95% CI:1.03-3.96; P=.04) were independently associated with suicidal ideation. CONCLUSIONS: Three out of the four correlates of suicidal ideation in medical inpatients are potentially modifiable factors: severe anxiety, depressive symptoms and poor social support. The fourth variable, prior suicide attempts, is not modifiable but should serve as a red flag to suspect and investigate current suicide risk. These findings highlight the importance of suicidal ideation as a proxy for the distress that is incumbent upon physicians to manage if they wish to provide excellent and comprehensive inpatient care.

Ideação suicida em pacientes internados em enfermarias de clínica médica: prevalência e sintomas depressivos / Suicidal ideation in patients admitted to general medical wards: prevalence and associated depressive symptoms

OBJETIVO: Verificar a frequência de ideação suicida e os sintomas depressivos associados a ela nos pacientes internados em enfermarias de clínica médica. MÉTODOS: Todos os adultos consecutivamente admitidos nas enfermarias de clínica médica de um hospital universitário foram randomizados e avaliados durante a primeira semana de internação. Coletaram-se dados sociodemográficos e aplicaram-se: o Patient Health Questionnaire (a pergunta sobre ideação suicida), o Inventário Beck de Depressão e o índice Charlson de comorbidade física. Utilizaram-se os testes t de Student, do qui-quadrado e a regressão logística. RESULTADOS: Dos 1.092 sujeitos, 79 (7,2%) apresentaram ideação suicida. Na análise multivariada, foram capazes de discriminar esses pacientes, após controlar para sexo, idade, comorbidade física e presença de uma síndrome depressiva, os seguintes sintomas, quando presentes em intensidade moderada a grave: tristeza [RR: 3,18; IC 95% = 1,78-5,65; p < 0,001], sensação de fracasso [RR: 2,01; IC 95% = 1,09-3,72; p = 0,03], perda do interesse nas pessoas [RR: 2,69; IC 95% = 1,47-4,94; p = 0,001] e insônia [RR: 1,74; IC 95% = 1,05-2,89; p = 0,03]. CONCLUSÃO: Os pacientes internados no hospital geral em enfermarias clínicas apresentaram prevalência de 7,2% de ideação suicida. Alguns sintomas, quando presentes em intensidade moderada a grave, deveriam alertar ao clínico-geral para investigar a presença de ideação suicida: tristeza, sensação de fracasso, perda do interesse nas pessoas e insônia.

OBJECTIVE: To assess the prevalence of suicidal ideation and the depressive symptoms associated to it in medical inpatients. METHODS: All adults consecutively admitted to the medical wards of a University Hospital had their names recorded, were randomized and evaluated during the first week of admission. Socio-demographic data were collected and the Patient Health Questionnaire (question 9, assessing suicidal ideation), the Beck Depression Inventory and the Charlson comorbidity index were applied. The Student t test, chi-square test and logistic regression analysis were used. RESULTS: Of the 1,092 patients who composed the sample, 79 (7.2%) reported having suicidal ideation. In the multivariate analysis, after adjusting for gender, age, physical comorbidity and the presence of a depressive syndrome, the following symptoms when in moderate to severe degree discriminated patients who had suicidal ideation: sadness [RR: 3.18; CI 95% = 1.78-5.65; p < 0.001], feeling like a failure [RR: 2.01; CI 95% = 1.09-3.72; p = 0.03], loss of interest in people [RR: 2.69; CI 95% = 1.47-4.94; p = 0.001] and insomnia [RR: 1.74; CI 95% = 1.05-2.89; p = 0.03]. CONCLUSION: The prevalence of suicidal ideation in medical inpatients was 7.2%. When present in a moderate to severe degree, symptoms like sadness, feeling like a failure, loss of interest in people and insomnia should alert the medical team to assess suicidal ideation.