Pathophysiology and treatment of inherited bleeding disorders

Frank Leebeek obtained his medical degree and PhD degree at the Erasmus University in Rotterdam The Netherlands in 1990. He subsequently worked as a post-doctoral fellow at the University of North Carolina at Chapel Hill, USA. He was trained as a hematologist at the Erasmus University Medical Center in Rotterdam, where he became a staff member and was appointed full professor in 2009. He is chair of the Department of Hematology since 2017. He is coordinating a research team on haemostasis and thrombosis with several research topics, mainly inherited bleeding disorders, including von Willebrand disease and haemophilia. He is steering committee member of several studies on innovative treatments for patients with bleedings disorders, including gene therapy. He is the principal investigator of the Willebrand in the Netherlands (WiN) study and the WiN-Pro study. He has been secretary of the Dutch Society of Thrombosis and Haemostasis, chairman of the Dutch Hemophilia Doctor’s Organisation, and is currently a board member of the Dutch Society of Haematology and the European Hematology Association. He has been co-chair of the Scientific and Standardization Committee on von Willebrand Factor of the International Society on Thrombosis and Haemostasis. He was awarded the Swammerdam prize of the Dutch Society of Hematology in 2009. Dr Leebeek has (co-)authored over 425 scientific publications listed on PubMed, 20 book chapters and contributed to national and international treatment guidelines on haemophilia, von Willebrand’s disease and venous thrombosis.

Important scientific achievements

* Initiating the Willebrand in the Netherlands (WiN) study and the prospective WiN pro study revealed new insights in the pathogenesis, burden and treatment of von Willebrand disease.    

- discovering new mutations causing VWD in a large cohort of VWD patients

- establishing that VWD patients (children and adults) have a reduced quality of life

- providing evidence that VWD patients have a reduced risk of stroke and myocardial infarction

*Identifying the important role of VWF in the development of arterial thrombosis by performing case control studies and population based studies

- High levels of VWF are associated with an increased risk of arterial thrombosis

- Low ADAMTS13 activity is associated with the risk of stroke myocardial infarction and ischemic stroke

* Involved in several clinical studies on gene therapy in hemophilia A and B

- In the Erasmus MC we treated the first hemophilia A patient in The Netherlands with gene therapy

- We showed prolonged benefit (>5 years) of gene therapy in Hemophilia B 

Our research

Our current research interest is mainly focused on inherited bleeding disorders. In our hemophilia treatment center (HTC) we take care of over 400 patients with hemophilia and >1000 with von Willebrand disease (VWD). This enables us to perform large clinical studies on these bleeding disorders. We focus on optimizing treatment for these disorders, for instance to optimize dosing of coagulation factor concentrates (in collaboration with Dr Cnossen, pediatric hematology), but also collaborate and participate in industry-sponsored trials with new hemostatic treatments. In addition we have initiated the WiN studies, that included a large cohort of patients with VWD in The Netherlands in collaboration with other HTCs. We have collected data on diagnosis, symptoms, co-morbidities, treatment and quality of life. Additionally we have collected plasma and DNA. This enabled us to characterize these patients genetically and phenotypically in detail. An important research question is to find the determinants of bleeding in VWD. It is well known that there is a wide variability in bleeding phenotype in patients with VWD. This is partly caused by variability in VWF and FVIII plasma levels, but even in patients with comparable factor levels a strong variability in bleeding phenotype is observed. In collaboration with Dr Bierings and Dr van Moort we are studying the pathophysiological mechanism in individual patients with various types and genetic background of VWD by collecting ECFC and perform studies on trafficking and secretion of Von Willebrand factor. This will enable us to better predict genotype/phenotype interactions. Within this collaboration we also investigate strategies for gene therapy/ gene editing for VWD.  

Our team

Key publications