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>alpha6beta1, alphaIIbbeta3>alpha2beta1>CD36, alpha5beta1, alphavbeta3. 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.
- AFFINITY BINDING
de Witt, S. M., Swieringa, F., Cavill, R.
, Lamers, M. M., van Kruchten, R., Mastenbroek, T., Baaten, C., Coort, S.
, Pugh, N., Schulz, A., Scharrer, I., Jurk, K., Zieger, B., Clemetson, K. J., Farndale, R. W., Heemskerk, J. W., & Cosemans, J. M.
(2014). Identification of platelet function defects by multi-parameter assessment of thrombus formation
. Nature Communications
, . https://doi.org/10.1038/ncomms5257