Project 14

Management of hemorrhagic and thrombotic disorders

Within this theme clinical studies have been initiated in bleeding disorders, including von Willebrand disease (VWD) and haemophilia. The Von Willebrand disease in the Netherlands ("WiN") study is a nation-wide study coordinated by the Erasmus MC (PI Prof. dr. Frank W.G. Leebeek) on the clinical aspects of VWD. In this study more than 800 patients with moderate and severe VWD have been included. We have recently obtained funding to study in detail genotype-phenotype associations and are currently performing next generation sequencing and whole exome sequencing to obtain more insight in the genetic background of VWD. In addition, we collaborate in studies on new therapeutic options in VWD, including new recombinant VWF concentrate during surgery and as prophylaxis.

Ongoing studies in haemophilia include the "OPTI-CLOT" research program (Patient tailOred PharmacokineTIc-guided dosing of CLOTting factor concentrate in bleeding disorders)", an international multicenter study (PI Dr. M.H. Cnossen) aiming to implement PK-guided dosing of clotting factor replacement therapy by initiation of studies in all bleeding disorders to prove the implications of PK-guided dosing, to construct perioperative and prophylactic PK population models and to evaluate the cost-effectiveness of a PK-guided approach. The "DAVID" studies (PI Dr. M.J.H.A. Kruip), explore combination therapy of DDAVP and factor concentrate in hemophilia A. Recently, also the CRESCENDO (PI Dr. M.J.H.A. Kruip) and DoReMi (PI Dr. M.H. Cnossen) studies aiming to explore the implications of novel diagnostic tests in patients with an unexplained bleeding tendency and possible platelet disorders have been initiated. Prof Leebeek is principal investigator of a European multicenter Phase I/II gene therapy study in hemophilia B patients in collaboration with UniQure, in which we have successfully treated 3 patients in the Erasmus MC. 

The etiology, diagnosis and treatment of various clinical entities of venous thrombosis are also focus of our research. One of our interests is the site specificity of venous thrombosis, for instance hepatic and portal vein thrombosis. In collaboration with other partners we have initiated studies on prevention and treatment of arterial and venous thrombosis using direct acting oral anticoagulants in children and adults.

Principal InvestigatorsFWG Leebeek,  MJHA Kruip MH Cnossen, CH van Ommen
Co-InvestigatorsMPM de Maat, DC Rijken
PhD candidatesJ. Boender, L. Schütte, I van Moort, C.S.B. Veen, M. Rijkers, M.W. Swinkels, J.M. Heijdra, F. Atiq, EJ Huisman, A. Nederlof