Background: Many patients who are diagnosed with coronavirus disease 2019 (COVID-19) suffer from venous thromboembolic complications despite the use of stringent anticoagulant prophylaxis. Studies... Show moreBackground: Many patients who are diagnosed with coronavirus disease 2019 (COVID-19) suffer from venous thromboembolic complications despite the use of stringent anticoagulant prophylaxis. Studies on the exact mechanism(s) underlying thrombosis in COVID-19 are limited as animal models commonly used to study venous thrombosis pathophysiology (i.e. rats and mice) are naturally not susceptible to Severe Acute Respiratory Syn-drome Coronavirus 2 (SARS-CoV-2). Ferrets are susceptible to SARS-CoV-2 infection, successfully used to study virus transmission, and have been previously used to study activation of coagulation and thrombosis during influenza virus infection.Objectives: This study aimed to explore the use of (heat-inactivated) plasma and lung material from SARS-CoV-2-inoculated ferrets studying COVID-19-associated changes in coagulation and thrombosis. Material and methods: Histology and longitudinal plasma profiling using mass spectrometry-based proteomics approach was performed.Results: Lungs of ferrets inoculated intranasally with SARS-CoV-2 demonstrated alveolar septa that were mildly expanded by macrophages, and diffuse interstitial histiocytic pneumonia. However, no macroscopical or microscopical evidence of vascular thrombosis in the lungs of SARS-CoV-2-inoculated ferrets was found. Lon-gitudinal plasma profiling revealed minor differences in plasma protein profiles in SARS-CoV-2-inoculated ferrets up to 2 weeks post-infection. The majority of plasma coagulation factors were stable and demonstrated a low coefficient of variation.Conclusions: We conclude that while ferrets are an essential and well-suited animal model to study SARS-CoV-2 transmission, their use to study SARS-CoV-2-related changes relevant to thrombotic disease is limited. Show less
The aim of this thesis is to identify emerging risk factors for VTE. To achieve this goal, we describe the supposedly causal role of statin and glucocorticoid use (i.e. two drugs that can influence... Show moreThe aim of this thesis is to identify emerging risk factors for VTE. To achieve this goal, we describe the supposedly causal role of statin and glucocorticoid use (i.e. two drugs that can influence inflammation) with changes in hemostasis and VTE risk. Systemic glucocorticoid use increases the relative risk of first VTE by more than three-fold and confers an 5% absolute risk of recurrent VTE per year. On the other hand, rosuvastatin use may reduce the risk of first VTE by 40%. Although the mechanisms behind this association are not fully elucidated, this thesis shows that rosuvastatin is capable of decreasing the thrombin generation potential by 10% in patients with a prior VTE. This thesis has shown that both statins and systemic glucocorticoids can affect the risk of VTE, improving the knowledge on the influence of these two commonly prescribed drugs on VTE pathophysiology. These findings have the potential to further refine the assessment of VTE risk since they highlight that the use of these drugs should be considered when evaluating the risk of VTE. Finally, this thesis provides insight into new therapeutic approaches since the results underscore that treatment strategies on VTE prevention in patients already taken statins, which may be sufficient for VTE prevention, are lacking. Treatment strategies to prevent glucocorticoid-associated VTE are also needed. Show less
