De Maat Lab

Our research focusses on understanding the role of the coagulation system in thrombosis, with emphasis on fibrinogen and the fibrin network. The last step of the coagulation cascade is the conversion of the protein fibrinogen to fibrin. Fibrin forms long fibers that branch and ultimately form the network that stabilized the thrombus. Fibrinogen is a very heterogeneous molecule and we study the relationship between the different forms and the architecture of the fibrin network, such as fiber thickness and branching, strength, elasticity, fibrinolysis rate. We recently started collaborating with the TU Delft (prof. Gijsje Koenderink) on this subject. By understanding this relationship we hope to optimize patient treatment in thrombosis, delayed wound healing and bleeding.

 We still do not completely understand the mechanisms underlying arterial thrombosis and knowing these mechanisms will enable us to recognize high risk patients and to optimize treatment options. We search (using genetic variation and protein variation) patient and population studies for new mechanisms and biomarkers. We have been involved in several successfully completed studies on these aspects, including basic research, clinical trials and epidemiological (sub)studies (Rotterdam Study, ECAT, ECAPTURE, REGRESS, ATTAC). At the moment we participate in the Contrast consortium in patients with acute ischemic stroke to search for biomarkers that are associated with treatment effect.

• Biomarkers and outcome of stroke in the CONTRAST studies (PhD student Aarazo Barakzie)
• Immunothrombosis and atrial fibrillation (PhD student Martijn Tilly)
• Fibrin network properties under flow (PhD student Hande Eyisoylu)

• Hoppenbrouwers, T., Sultan AR, Abraham TE, Lemmens-den Toom N, Hansenova Manaskova S, Cappellen WA, Houtsmuller AB, van Wamel WJB, de Maat MPM, and van Neck JW. Protein A (SpA): a novel determinant of Neutrophil Extracellular Traps (NETs) by S. aureus. Front. Immunol. 2018;9:165
• de Maat MPM, van Schie M, Kluft C, Leebeek FW, Meijer P. Biological Variation of Hemostasis Variables in Thrombosis and Bleeding: Consequences for Performance Specifications. Clin Chem. 2016;62:1639-46
• Sonneveld MA, Kavousi M, Ikram MA, Hofman A, Rueda Ochoa OL, Turecek PL, Franco OH, Leebeek FW, de Maat MPM. Low ADAMTS-13 activity and the risk of coronary heart disease - a prospective cohort study: the Rotterdam Study. J Thromb Haemost. 2016;14:2114-20
• de Vries PS, Chasman DI, Sabater-Lleal M, …… de Maat MPM …… . A meta-analysis of 120,246 individuals identifies 18 new loci for fibrinogen concentration. Hum Mol Genet. 2015; 25: 358-70
• Pieters M, de Maat MPM. Diet and haemostasis - a comprehensive overview. Blood Rev. 2015;29:231-241

Within Erasmus MC, research on venous and arterial thrombosis and bleeding diseases is carried out by the Thrombosis and Hemostasis Research Group, mostly in collaborations with researchers from different departments:

• Epidemiology (Prof.dr. M.A. Ikram, Prof.dr. M. Kavousi, dr. F. Wolters: epidemiology of coagulation and arterial thrombosis and dementia).
• (Experimental) cardiology (dr. H.H.D.M. van Beusekom, dr. K. Kooiman, dr. K. Lattwein: relationship coagulation, biofilms and thrombosis).
• Pediatric hematology (Prof.dr. M.H. Cnossen, dr. C.H. van Ommen: coagulation in children).
• Microbiology (dr. W.J.B. van Wamel: interaction of coagulation, bacteria and NETosis).
• Neurology ( Prof.dr. D.W.J. Dippel: relationship coagulation and stroke).
• Pathology ( Prof.dr. A.B. Houtsmuller, dr. W.A. van Cappellen: live imaging of clot formation and NETosis).
• Plastic suirgery (dr. J.E. van Neck: coagulation and wound healing).

National

Within the Netherlands, the research group has established a strong position by conducting high quality biochemical, translational and clinical research. It participates in national studies, both investigator-initiated and industry-initiated studies, such as the prospective population Rotterdam study, the national multicenter Willebrand in the Netherlands (WiN) study (initiated from Erasmus MC) in patients with (moderate-)severe von Willebrand disease, OptiClot and DAVID study, in hemophilia patients for effective and patient-specific treatment, and the CONTRAST consortium to improve the treatment of cerebral infarction (especially the departments of neurology, vascular medicine and radiology of the Academic Centers and large peripheral hospitals).

Collaboration also exists with TU Delft (Prof.dr. G. Koenderink) on mechanical properties of the fibrin network, with the MUMC on the relationship between fibrin structure and the architecture of thrombi removed in cerebral or myocardial infarction (Vascular Medicine (Prof. Dr. H. ten Cate)) and with LUMC (Prof. J. Eikenboom) on the mechanisms of secretion and clearance in patients with von Willebrand factor disease in the WIN study.

International

Within the area of Biochemistry of Thrombosis and Hemostasis, international cooperation is being established in research on fibrinogen with many centers, most important are the collaboration with Denmark (Prof. Else Bladbjerg and dr. A.M. Bloch Munster: fibrinogen variants and clot structure), South Africa (Prof. M. Pieters: fibrinogen and fibrin structure, genetic variation in black South Africans).

Prof. M.P.M. (Moniek) de Maat, PhD, Principal investigator

Samantha Donse-Donkel, MD
Judith de Vries, MSc
Anouchska Autar, MD
Tyro Damiana, Msc
Tanno de Man