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: 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, Judith M E M Cosemans
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 4257 (Jul 16 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 25027852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Biological Assay (methods)
• Computational Biology
• Female
• Humans
• Male
• Middle Aged
• Platelet Aggregation (physiology)
• Thrombosis (diagnosis, metabolism)
• Young Adult