Identification of platelet function defects by multi-parameter assessment of thrombus formation

Susanne M. de Witt, Frauke Swieringa, Rachel Cavill, Moniek M. E. Lamers, Roger van Kruchten, Tom Mastenbroek, Constance Baaten, Susan Coort, Nicholas Pugh, Ansgar Schulz, Inge Scharrer, Kerstin Jurk, Barbara Zieger, Kenneth J. Clemetson, Richard W. Farndale, Johan W. M. Heemskerk () and Judith M.E.M. Cosemans ()
Additional contact information
Susanne M. de Witt: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
Frauke Swieringa: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
Rachel Cavill: Maastricht University
Moniek M. E. Lamers: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
Roger van Kruchten: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
Tom Mastenbroek: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
Constance Baaten: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
Susan Coort: Maastricht University
Nicholas Pugh: Anglia Ruskin University
Ansgar Schulz: Pediatric Centre, University Clinic Ulm, Universitätsklinik Für Kinder- und Jugendmedizin
Inge Scharrer: Center for Thrombosis and Haemostasis (CTH), Universitätsmedizin der Johannes Gutenberg, University of Mainz
Kerstin Jurk: Center for Thrombosis and Haemostasis (CTH), Universitätsmedizin der Johannes Gutenberg, University of Mainz
Barbara Zieger: University Medical Centre Freiburg
Kenneth J. Clemetson: Inselspital, University of Bern
Richard W. Farndale: University of Cambridge
Johan W. M. Heemskerk: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
Judith M.E.M. Cosemans: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5257

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