ABSTRACT
Background: Thrombosis is a frequent and severe complication in COVID-19 patients admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in COVID-19 patients. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. Aim(s): To investigate if LA is associated with thrombosis in critically ill COVID-19 patients. Method(s): The presence of LA and other antiphospholipid antibodies was assessed in COVID-19 patients admitted to the ICU. Informed consent was obtained by an opt-out approach and the study was approved by the local medical ethical committee. LA was determined with dilute Russell's Viper Venom Time (dRVVT) and LA-sensitive Activated Partial Thromboplastin Time (aPTT) reagents. Statistical analysis to study the association of LA and other antiphospholipid antibodies with thrombosis occurrence was performed using logistic regression. Result(s): Out of 169 COVID-19 patients, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA;of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT and eight (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.4 (95%-CI: 1.1-5.4), which increased to 5.1 (95%-CI: 1.7-15.4) in patients on or below the median age of this study population (64 years). LA-positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients younger than 65 years (OR: 4.2, 95%-CI: 1.5-11.7). Conclusion(s): LA on admission is strongly associated with thrombosis in critically ill COVID-19 patients, especially in patients <65 years of age.
ABSTRACT
Background: Coagulopathy and inflammation are hallmarks of COVID-19 and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19. Mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood. Aim(s): In this study, we aimed to investigate a possible role of NETs-driven coagulation factor XII (FXII) activation in COVID-19- related thrombo-inflammation. Method(s): We performed comprehensive proteomics and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We compared FXII and DNase1 activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced FXII activation using a chromogenic substrate assay. Result(s): FXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients over controls. Active FXII (FXIIa) was increased in plasma of COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII activation in COVID-19. Accumulation of NETs in COVID-19 was at least in parts due to impaired DNA clearance by extracellular DNases. In plasma from COVID-19 patients, DNase1 substitution improved NET dissolution and reduced FXII activation in vitro. Conclusion(s): Collectively, our study shows that the NETs/FXIIa axis contributes to procoagulant and proinflammatory reactions in COVID-19. Targeting NETs and FXIIa may offer a potential therapeutic strategy for interfering with the COVID-19 lung pathology.
ABSTRACT
Background: SARS-CoV- 2 infection is associated with an increased incidence of thrombosis. Aim(s): By studying the fibrin network structure of COVID-19 patients, we aimed to unravel pathophysiological mechanisms that contribute to this increased risk of thrombosis. This may contribute to optimal prevention and treatment of COVID-19 related thrombosis. Method(s): In this case-control study, we collected plasma samples from intensive care unit (ICU) patients with COVID-19, with and without confirmed thrombosis, between April and December 2020. Additionally, we collected plasma from COVID-19 patients admitted to general wards without thrombosis, from ICU patients with pneumococcal infection, and from healthy controls. Fibrin fiber diameters and fibrin network density were quantified in plasma clots imaged with stimulated emission depletion (STED) microscopy and confocal microscopy. Finally, we determined the sensitivity to fibrinolysis. Ethical approval was obtained and written informed consent was obtained or an opt-out procedure was in place. Result(s): COVID-19 ICU patients (n = 37) and ICU patients with pneumococcal disease (n = 7) showed significantly higher fibrin network densities and longer plasma clot lysis times than healthy controls (n = 7) (Figure 1). No differences were observed between COVID-19 ICU patients with and without thrombosis, or ICU patients with pneumococcal infection. At a second time point, after thrombosis or at a similar time point in patients without thrombosis, we observed thicker fibers and longer lysis times in COVID-19 ICU patients with thrombosis (n = 19) than in COVID-19 ICU patients without thrombosis (n = 18). Conclusion(s): Our results suggest that severe COVID-19 is associated with a changed fibrin network structure and decreased susceptibility to fibrinolysis. Since these changes were not exclusive to COVID-19 patients, they may not explain the increased thrombosis risk. (Figure Presented).
ABSTRACT
Background : Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and high incidence of thrombotic events (TE). Platelet hyperreactivity has been reported in COVID-19 patients and might contribute to TE development. Aims : To study platelet reactivity in hospitalized COVID-19 patients and to determine a possible association with the clinical outcomes thrombosis and all-cause mortality. Methods : 79 hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality. Results : The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not (median age of 55 versus 70 years;adjusted odds ratio (AOR), 0.96 per 1 year of age [95% CI, 0.92-1.00];P = 0.042). Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a TE than patients that were not (18% versus 54%;adjusted odds ratio, 0.18 [95% CI, 0.04-0.82];P = 0.026). Conversely, having asthma strongly increased the risk on TE development (adjusted odds ratio, 6.4 [95% CI, 1.17-35.4];P = 0.032). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients ( n = 79) and COVID-19 negative hospitalized control patients ( n = 24), nor between COVID-19 survivors or non-survivors. However, patients showed decreased platelet reactivity in response TRAP-6 following TE development compared to patients without TE. Conclusions : We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation.
ABSTRACT
The coronavirus pandemic (COVID-19) has served as a call-to-arms in preparing practices for the next disaster whether it is another infectious disease or a flood, hurricane, earthquake, a sustained power outage, or something else. A group of predominantly core aesthetic physicians discussed the various aspects of their office procedures that warrant consideration in a proactive approach to the next pandemic/disaster-related event. This guide does not set a standard of practice but contains recommendations that may avoid some of the "lessons learned" with the COVID-19 pandemic. In this paper, the board-certified core aesthetic physicians classified these recommendations into four generalized areas: Practice Management;Supplies and Inventory;Office Staffing Considerations and Protocols;and Patient Management Strategies. Proactive strategies are provided in each of these categories that, if implemented, may alleviate the processes involved with an efficient office closure and reopening process including, in the case of COVID-19, methods to reduce the risk of transmission to doctors, staff, and patients. These strategies also include being prepared for emergency-related notifications of employees and patients;the acquisition of necessary equipment and supplies such as personal protective equipment;and the maintenance and accessibility of essential data and contact information for patients, vendors, financial advisors, and other pertinent entities.J Drugs Dermatol. 2021;20(1):10-16. doi:10.36849/JDD.2021.5803.