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

S. M. de Witt, F. Swieringa, R. Cavill, M. M. Lamers, R. van Kruchten, T. Mastenbroek, C. Baaten, Susan Coort, N. Pugh, A. Schulz, I. Scharrer, K. Jurk, B. Zieger, K.J. Clemetson, R.W. Farndale, J.W. Heemskerk, J.M. Cosemans

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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>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.
Original languageEnglish
Article number4257
Number of pages13
JournalNature Communications
Volume5
DOIs
Publication statusPublished - Jul 2014

Keywords

  • VON-WILLEBRAND-FACTOR
  • AFFINITY BINDING
  • COLLAGEN
  • ADHESION
  • FLOW
  • ACTIVATION
  • FIBRINOGEN
  • RECEPTOR
  • SITE
  • SHEAR

Cite this

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, 5, [4257]. https://doi.org/10.1038/ncomms5257