Epidemiology of thrombosis and bleeding

Ambition

Our ultimate goal is to reduce the burden of disease related to thrombosis and bleeding, by understanding their causes and in particular preventing their occurrences.

This is approached in several ways:

1) by finding novel risk factors for thrombosis, either genetic or acquired, and understanding their mechanism. This is done in large international collaborations (CHARGE, INVENT) for genetic data, and in our own studies (MEGA, THE-VTE, AT-AGE, TERA) for environmental causes, ranging from exposure to endogenous and exogenous hormones (corticosteroids, sex hormones, oral contraceptives), obesity and SARS-CoV-2 vaccination.

2) by identifying individuals with different magnitudes of risk of thrombosis who will benefit from targeted prophylactic treatment with currently available medication. To this effect we developed risk scores (TRIP(cast) for patients with lower-leg trauma, TRIP(scopy) for patients undergoing knee arthroscopy, TRIP(plasty) for patients undergoing knee or hip replacement). Similar work is performed for high risk patients, i.e., those with cancer or a history of venous thrombosis.  With the use of established and novel genetic risk factors, genetic risk scores will also be developed, both for first and recurrent thrombosis, and also for groups with increased risk such as oral contraceptive users.

3) By finding causes for postpartum bleeding and in neonates, as well as peri-operatively and in critically ill patients.

4) By studying the medical and social conditions of patients with haemophilia in the 50-year ongoing Haemophilia in the Netherlands (HiN1-Hin6) projects, and to study risk factors for inhibitor development in these patients, as well as predictors for immunotolerance treatment.

Position in (inter)national context

The research performed at the department of Clinical Epidemiology in the field of Thrombosis and Bleeding is unique in the world, as it coordinates and integrates different types of studies and methods:

• Large databases from case-control and cohort studies as well as randomized controlled trials.
• Extensive genotyping and phenotyping in these datasets on clinical and laboratory data
• Nationwide data from Statistics Netherlands
• Detailed laboratory studies in smaller, nested datasets
• Application of state-of-the-art statistical methods 

  This work is performed in close collaboration with other departments of the LUMC (Internal Medicine, Orthopaedics, Obstetrics, Neonatology, Intensive Care), many national hospitals and university medical centers, the Federation of Dutch Anticoagulation Clinics, medical and scientific societies and internationally with colleagues in Tromsø (Norway), Marseille and Bordeaux (France), Aarhus and Copenhagen (Denmark), London (UK), Seattle (USA), Mainz (Germany) and Milan (Italy)

  The program attracts funding from national (ZonMw, Thrombosis foundation, Ministery of Health) and international (EU) funding bodies.Nationwide data from Statistics Netherlands

  Detailed laboratory studies in smaller, nested datasetsNationwide data from Statistics Netherlands

Highlights and achievements

As an illustration, some highlights and achievements of the past decades are described here:

• Knowledge on (new) risk factors for venous thrombosis, such as Factor V Leiden and other genetic risk factors, several coagulation factor levels, (sex) hormone use or status (e.g. hyperthyroidism) but also oral contraceptive use), comorbidities (cancer, trauma, infection)
• Development and validation of several risk prediction models and genetic risk scores for identification of patients at high risk of venous thrombosis or for bleeding
• Establishment of non-effectiveness of anticoagulant treatment after lower-leg plaster cast or knee arthroscopy, including according change of national guidelines
• Development of methods to measure the quality of treatment with vitamin K antagonists (Time-in-Therapeutic Range, TTR).
• Assessment of changes in mortality in haemophilia patients from 1972 onwards
• Findings on immunogenicity of particularly recombinant FVIII products in inhibitor development in haemophilia.