title: Identification of platelet function defects by multi-parameter assessment of thrombus formation.
abstract: Assays measuring platelet aggregation (thrombus formation) at arterial shear rate mostly use collagen as only platelet-adhesive surface. Here we report a multi-surface and multi-parameter flow assay to characterize thrombus formation in whole blood from healthy subjects and patients with platelet function deficiencies. A systematic comparison is made of 52 adhesive surfaces with components activating the main platelet-adhesive receptors, and of eight output parameters reflecting distinct stages of thrombus formation. Three types of thrombus formation can be identified with a predicted hierarchy of the following receptors: glycoprotein (GP)VI, C-type lectin-like receptor-2 (CLEC-2)>GPIb>α6β1, αIIbβ3>α2β1>CD36, α5β1, αvβ3. Application with patient blood reveals distinct abnormalities in thrombus formation in patients with severe combined immune deficiency, Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, May-Hegglin anomaly or grey platelet syndrome. We suggest this test may be useful for the diagnosis of patients with suspected bleeding disorders or a pro-thrombotic tendency.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: de Witt
authors.affiliation: 1] Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands [2].
authors.forename: Frauke
authors.initials: F
authors.lastname: Swieringa
authors.affiliation: 1] Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands [2].
authors.forename: Rachel
authors.initials: R
authors.lastname: Cavill
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Moniek M E
authors.initials: MM
authors.lastname: Lamers
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Roger
authors.initials: R
authors.lastname: van Kruchten
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Mastenbroek
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Constance
authors.initials: C
authors.lastname: Baaten
authors.affiliation: Department of Bioinformatics, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: Coort
authors.affiliation: Anglia Ruskin University, East Rd, Cambridge CB11PT, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pugh
authors.affiliation: Pediatric Centre, University Clinic Ulm, Universitätsklinik Für Kinder- und Jugendmedizin, Eythstrasse 24, D-89075 Ulm, Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Center for Thrombosis and Haemostasis (CTH), Universitätsmedizin der Johannes Gutenberg, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Scharrer
authors.affiliation: Center for Thrombosis and Haemostasis (CTH), Universitätsmedizin der Johannes Gutenberg, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jurk
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Centre Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zieger
authors.affiliation: Department of Haematology, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Clemetson
authors.affiliation: Department of Biochemistry, University of Cambridge, Downing Site, Cambridge CB2 1QW, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
authors.affiliation: 1] Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands [2].
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
authors.affiliation: 1] Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands [2].
authors.forename: Judith M E M
authors.initials: JM
authors.lastname: Cosemans
mesh_terms: D000328:Adult; D001681:Biological Assay / Q000379:methods*; D019295:Computational Biology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000502:physiology; D013927:Thrombosis / Q000175:diagnosis* / Q000378:metabolism*; D055815:Young Adult