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Samenvatting
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Binnen het project: "Caging the dragon: translational approach to unravel and prevent COVID-19 associated thrombosis" hebben wij een samenwerking opgezet met verschillende onderzoekers van meerdere universiteiten, ziekenhuizen, specialisten, verzorgingstehuizen, sanquin en trombosediensten om de verschillende onderzoeksvragen over veneuze trombose bij corona patiënten te beantwoorden. Wij proberen een antwoord te geven waarom veneuze trombose bij COVID-19 patiënten vaker optreedt, hoe deze trombose ontstaat en hoe deze trombose het best kan worden behandeld en kan worden voorkómen en wat het lange termijn effect van deze veneuze trombose op de gezondheid kan zijn. Om deze vragen te beantwoorden zullen wij gegevens verzamelen van de opnames aan het begin van de corona epidemie. 46 ziekenhuizen hebben op dit moment aangegeven mee te willen werken aan dit project. Wij zijn hard bezig om dit juridische en organisatorisch te regelen zodat wij van een grote groep gegevens kunnen verzamelen en analyseren. De eerste definitieve resultaten worden de komende maanden verwacht.

Resultaten
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Samenvatting van de aanvraag

Samenvatting
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RELEVANCE

The incidence of venous thromboembolic events (VTE) in COVID-19 patients is remarkably high, up to 48% on ICU despite thromboprophylaxis, suggesting a procoagulant state. Several underlying mechanisms have been suggested. To find the best possible treatment of COVID-19 patients we need to understand the pathogenesis and risk factors as well as the safety and efficacy of currently prescribed thromboprophylaxis and treatment.

 

OBJECTIVE AND STRATEGY

OVERALL OBJECTIVE: to understand and prevent VTE in COVID-19 patients and optimize acute treatment and long term health of COVID-19 patients with VTE

A. PATHOGENESIS

IN VIVO

OBJECTIVE: To unravel pathophysiological mechanisms that cause COVID-19 associated coagulopathy

STRATEGY: We will investigate 1) Prothrombotic antiphospholipid antibodies 2) Fibrinolysis 3) Coagulation and anticoagulants 4) Thrombus composition 5) OMICS. Multi-center expert teams are in place to investigate responsible mechanisms in plasma samples and tissue specimens. Most areas contain hypothesis-driven research with existing technologies, the OMICS approach should provide new insights in a hypothesis-free manner.

IN VITRO

OBJECTIVE: To identify the molecular mechanisms of SARS-CoV-2 induced thrombosis using in vitro infection models of pulmonary vascular bed. Tropism of SARS-CoV-2-infected endothelial cells will be compared to other respiratory viruses that cause VTE.

STRATEGY: In vitro models study SARS-CoV2 kinetics and dynamics and their effect on endothelial cells and co-culture models and their role in inducing a procoagulant state. Data will be related to pathology observations in autopsies.

 

B. THROMBOPROPHYLAXIS AND TREATMENT OF THROMBOSIS

OBJECTIVE: To define the optimal strategies for prevention and treatment of VTE in COVID-19 patients

STRATEGY: Combining all available observational evidence from established registries and targeted collection in cohorts, changes in prophylaxis can be linked to outcomes. We facilitate participation in REMAP-CAP-COVID-19 study to compare therapeutic dose with standard dose prophylaxis. Using global clotting assays on biobanked samples, biochemical efficacy of anticoagulation treatment is evaluated.

 

C. BIOMARKERS AND PREDICTION OF THROMBOSIS

OBJECTIVE: To predict the risk of VTE in admitted COVID-19 patients

STRATEGY: Patients data will be collected and VTE patients identified. Dynamic prediction models will be developed to estimate individual VTE risks. The predictive values will be compared for different mechanistic pathways, VTE phenotypes for ICU and non-ICU patients.

 

D. LONG TERM CONSEQUENCES OF VTE

OBJECTIVE: To assess the impact and long-term consequences of VTE in COVID-19 patients

STRATEGY: COVID-19 patients will be followed for long-term effects on pulmonary and cardiac function, functional status and quality of life. The incidence of post-VTE syndrome will be determined compared to COVID-19 patients without VTE and non-COVID-19 VTE patients.

 

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