Pathophysiology and etiology of thrombosis

Insight into the pathophysiology and co-morbidities that underlie thrombotic disease has increased in the last decades. Nevertheless, how genetic and acquired risk factors impact thrombosis needs better characterization to facilitate improved prevention, diagnosis and treatment options. In addition, diseases such as cancer and Cushing’s syndrome increase the risk of thrombosis, but the exact underlying mechanism is not well-defined. In this programme, we aim to uncover these links using a compl

SPECIFIC AIMS OF THE RESEARCH PROGRAMME

It is well known that certain clinical conditions and situations are associated with an increased risk of venous thrombosis. Examples are pregnancy, oral contraceptive use, trauma, surgery and cancer. The exact mechanisms underlying these increased risks, and individual risk factors that further raise the risk are to some extent known, but a lot of mechanistic insight is still lacking. This is firstly targeted in our basic research projects, that mainly focus on cancer, but also translated into a more clinical part where we combine extensive laboratory and clinical data from several sources with statistical methods that allow causal reasoning to obtain this knowledge.

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SPECIFIC AIMS OF THE RESEARCH PROGRAMME

It is well known that certain clinical conditions and situations are associated with an increased risk of venous thrombosis. Examples are pregnancy, oral contraceptive use, trauma, surgery and cancer. The exact mechanisms underlying these increased risks, and individual risk factors that further raise the risk are to some extent known, but a lot of mechanistic insight is still lacking. This is firstly targeted in our basic research projects, that mainly focus on cancer, but also translated into a more clinical part where we combine extensive laboratory and clinical data from several sources with statistical methods that allow causal reasoning to obtain this knowledge.

In several ongoing projects we pursue this, amongst others for cancer patients, for patients who need hip- or knee replacement, for exposure to hormones (endogenous and exogenous), and for patients with Covid-19. These studies use data from the MEGA-study, the AT-AGE-study, THE-VTE-study, the POT-(K)CAST study and the L-TRRiP study, but also nationwide data from several registries.

The interplay between cancer and hypercoagulation is a major focus area within our research program. Fist of all, we aim to determine impact of clinical determinants such as cancer type and cancer treatment on thrombotic risk in oncological patients.

These studies are complemented with transcriptomics approaches in tumors and quantitative proteomics in plasma from cancer patients to elucidate pathways that are involved in cancer-associated thrombosis. Finally, we aim to integrate clinical parameters, genes and proteins involved in cancer-associated thrombosis in preclinical and organ-on-a-chip models to better understand their roles in thrombotic risk

Next to the impact of cancer on thrombosis, we also investigate the reciprocal link, i.e. effects of hypercoagulability on cancer progression. More specifically, we investigate the mechanistic role of coagulation factor-dependent signal transduction in cancer progression, but also direct effects of thrombosis on cancer progression.

INTERNATIONAL POSITION OF THE RESEARCH PROGRAMME

We locally collaborate with the departments of Endocrinology, Oncology, Pathology, Surgery, Orthopaedics and Neurology.

We collaborate nationally with all UMCs and several non-academic centers throughout the Netherlands. On an international level, we collaborate with universities in Tromsø, Aarhus, Belo Horizonte, Seattle, London,

Work of this research programme is published in journals such as Journal of Thrombosis and Haemostasis, New England Journal of Medicine, Nature Medicine, Proceedings of the National Academy of Sciences and Blood.

Research groups