The World Thrombosis Day, a collaborative movement, has been successfully raising awareness for thrombosis since 2014. At Amsterdam UMC, the tradition of thrombosis research goes back a lot longer. Research areas span all clinical domains of thromboembolism, from prevention to diagnosis and from etiology to treatment. The flip side of the coagulation coin, bleeding disorders, is also a subject of our research interests.

One might say that our research directly stems from clinical questions. Although we have a broad scope, focus is needed, as in any research program, in order to be successful. A key to success is the balance between pharmaceutical company-initiated research with investigator-initiated studies.

For instance, our memberships on steering committees of large research programs for novel anticoagulant drugs and antidotes: is academically satisfying, important for networking, provides a means to initiate academic studies and generates pilot studies for grant applications. Being an active recruiting site, with the help of the clinical trial unit of the Department of Vascular Medicine, is a big asset.

A common denominator in our research lines is special populations. For instance, patients with cancer are not only at increased risk of thrombosis, but also have a higher risk of bleeding and need a specific approach for diagnosis and optimal anticoagulation.

Furthermore, patients with thrombosis have an increased risk of having an underlying malignancy. We are currently evaluating the applicability of a test that uses tumor-educated platelets in patients with otherwise unexplained thrombosis or pulmonary embolism. This is being done under the supervision of Dr. Nick van Es and in collaboration with Prof. Tom Wurdinger.

1 in 4 people worldwide die from conditions caused by thrombosis

There is a an extremely exciting development in gene therapy for patients with haemophilia. At Amsterdam UMC, the first Dutch patient received this life changing gene therapy for haemophilia B, under the supervision of Dr. Michiel Coppens. Since then, haemophilia A patients have also successfully undergone this experimental therapy.

Pregnant women constitute another special population. Pregnancy is a risk factor for thrombosis, and pulmonary embolism is the number one cause of maternal death in Western societies.

For young women who have experienced thrombosis, prevention with injections of the anticoagulant low-molecular-weight heparin (LMWH) during a subsequent pregnancy and the postpartum period is indicated. However, to date there are no adequate data on the optimal prophylactic dose, as research in this population has been largely neglected. Observational cohort studies have shown conflicting results.

This was the motivation to initiate a large randomized controlled trial that simply compares two doses of LMWH, the Highlow Study. The trial started recruiting in 2013, and has subsequently been expanded to eight countries and has recruited almost 1000 patients to date.

Although the study design is simple and pragmatic, funding has been extremely challenging. The success story of this randomized trial is a kind of “wiki-funding” with a modest startup grant from a pharmaceutical company, to Ministry of Health grants in France and Ireland.

photo by Jeroen van Kooten
left: Saskia Middeldorp, dept. Vascular Medicine

Another landmark trial that is ongoing is the ALIFE2 trial, a study that investigates whether anticoagulant treatment with LMWH improves the chance of a successful pregnancy in women with an inherited tendency to form blood clots (thrombophilia) and who have had two or more miscarriages.

This trial was funded by my VIDI trial and an NHS Research for Patient Benefit Grant in the UK. Both trials will complete recruitment within one year from now, and I can’t wait until the results can be analyzed, made public and have an impact on guidelines and patient care.

Finally, the importance of translational research is well acknowledged. We have a biobank of antiphospholipid syndrome patients, and are currently doing an intervention trial (ROMAS) in women with obstetric antiphospholipid syndrome, to assess how manipulating the microbiome with the antibiotic vancomycin affects antibodies. This is being done under the supervision of Dr. Thijs van Mens, in collaboration with Prof. Jan Voorberg and Prof. Joost Meijers.

About one thing I am quite confident: thrombosis and haemostasis research at Amsterdam UMC is alive and kicking!