Cerebral Venous and Sinus Thrombosis with Immunological Pathogenesis: VITT and Pre-VITT

In this review, we summarise the current knowledge on vaccine-induced immune thrombotic thrombocytopenia (VITT) and new insights into its underlying pathogenesis. VITT is characterised by severe thromboses occurring 5-20 days after vaccination with an adenoviral vector-based SARS-CoV-2 vaccine (AstraZeneca or Johnson & Johnson). Thromboses typically involve the cerebral sinus and venous system. Routine laboratory analyses show thrombocytopenia and high D-dimer levels. The pathogenesis is based on immunological processes similar to those in heparin-induced thrombocytopenia. Accordingly, VITT is associated with high-titre immunoglobulin G directed against platelet factor 4 (PF4). Interaction with adenoviral vector-based vaccines leads to modifications of PF4 allowing antibody-producing cells to identify PF4. Anti-PF4 antibodies activate platelets through FcgammaIIa receptors. The detection of platelet-activating anti-PF4 antibodies confirms the diagnosis of VITT. Treatment is based on anticoagulation, which inhibits thrombin itself or thrombin formation, and high-dose intravenous immunoglobulin G, which inhibits cell activation via FcgammaIIa receptors. In severe cases, plasma exchange could also be an option. In some patients, a pre-VITT syndrome precedes VITT. Pre-VITT patients typically present with severe headache before thromboses are manifest. The early identification of a pre-VITT syndrome allows for the prevention of thrombotic complications. The specific dynamics of the immune reaction in VITT correspond to a transient, secondary immune response. Current studies address how PF4 binds to different adenoviral proteins and investigate the functional role of other vaccine components. Some of these factors contribute to the induction of a pro-inflammatory danger signal that triggers the first stage of VITT pathogenesis. In the second stage, high-titre anti-PF4 antibodies activate platelets and granulocytes. In a process called NETosis (neutrophil extracellular traps), activated granulocytes release DNA. Anti-PF4 antibodies then bind to complexes of PF4 and DNA. This enhances further cell activation via Fcgamma receptors and consequently also the formation of thrombin. At the end of the article, we comment on how the current knowledge on VITT may influence global vaccination campaigns against SARS-CoV-2 and we address how anti-PF4 antibodies may be involved in recurrent arterial and venous thromboses not associated with VITT and HIT. Copyright © 2022 Georg Thieme Verlag. All rights reserved.

The experience of an emergency intensive care unit during the COVID-19 pandemic: A retrospective cohort study Emergency intensive care unit experiences due to COVID-19

Aim: The availability of an intensive care unit in the emergency departments (EDICU) is one of the most important issues discussed recently in terms of increasing the quality of emergency patient care. In this study, we aimed to investigate the clinical characteristics and factors affecting the mortality in patients with COVID-19. Material and Methods: This is a retrospective study of patients with COVID-19 hospitalized in EDICU. Patients were divided into mortality and survival groups, and the clinical characteristics of these groups were compared. Results: A total of 38 patients were included;47.4% (n = 18) were in the survival group. Oxygen saturation level was significantly different between the mortality and survival groups [78.0% (63.7-83.0) vs 88.5% (81.5-93.2), p = 0.001). Patients in the mortality group had higher plasma levels of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), lactate, ferritin and D-dimer. Univariate regression analysis showed that oxygen saturation, LDH, CRP and endotracheal intubation (ETI) were significant markers in predicting mortality (p = 0.011, p = 0.035, p <0.001, respectively). A CRP level >= 91.9 mg/L predicts mortality with a sensitivity of 66.6% and a specificity of 80.0% (AUC: 0.781, 95% CI: 0.617- 0,898). Discussion: This study showed that oxygen saturation, ETI, LDH and CRP levels were significantly successful in predicting mortality. Therefore, early administration of antibiotherapy and timely use of ETI may increase the quality of patient care.

The experience of an emergency intensive care unit during the COVID-19 pandemic: A retrospective cohort study

Aim: The availability of an intensive care unit in the emergency departments (EDICU) is one of the most important issues discussed recently in terms of increasing the quality of emergency patient care. In this study, we aimed to investigate the clinical characteristics and factors affecting the mortality in patients with COVID-19. Material and Methods: This is a retrospective study of patients with COVID-19 hospitalized in EDICU. Patients were divided into mortality and survival groups, and the clinical characteristics of these groups were compared. Results: A total of 38 patients were included;47.4% (n = 18) were in the survival group. Oxygen saturation level was significantly different between the mortality and survival groups [78.0% (63.7-83.0) vs 88.5% (81.5-93.2), p = 0.001]. Patients in the mortality group had higher plasma levels of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), lactate, ferritin and D-dimer. Univariate regression analysis showed that oxygen saturation, LDH, CRP and endotracheal intubation (ETI) were significant markers in predicting mortality (p = 0.011, p = 0.035, p <0.001, respectively). A CRP level ≥ 91.9 mg/L predicts mortality with a sensitivity of 66.6% and a specificity of 80.0% (AUC: 0.781, 95% CI: 0.617-0,898). Discussion: This study showed that oxygen saturation, ETI, LDH and CRP levels were significantly successful in predicting mortality. Therefore, early administration of antibiotherapy and timely use of ETI may increase the quality of patient care.