Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms5257
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Funding
- Center for Translational Molecular Medicine (INCOAG)
- Dutch Heart Foundation [2011T6]
- Landsteiner Foundation for Blood Transfusion Research [1006]
- ZonMW [MKMD 114021004]
- BHF programme grant [RG/09/003/27122]
- Wellcome Trust Biomedical Resource grant [094470/Z/10/Z]
- British Heart Foundation [RG/09/003/27122] Funding Source: researchfish
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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 > alpha(6)beta(1), alpha(IIb)beta(3)>alpha(2)beta(1)>CD36, alpha(5)beta(3), alpha(v)beta(3). 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.
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