Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation

Wenche Jy, J. J. Jimenez, L. M. Mauro, L. L. Horstman, P. Cheng, E. R. Ahn, C. J. Bidot, Y. S. Ahn

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Endothelial microparticles (EMP) released from activated or apoptotic endothelial cells (EC) are emerging as useful markers for detection of EC dysfunction. Our recent observation that EMP carry von Willebrand factor (vWf) led us to investigate their interaction with platelets. EMP were incubated with normal washed platelets in the presence or absence of ristocetin, then platelet aggregates were measured by flow cytometry. In the absence of ristocetin, negligible EMP conjugated with platelets (< 5%) but in the presence of ristocetin (1 mg mL-1), EMP induced up to 95% of platelets to aggregate. EMP-platelet interaction was 80% blocked by anti-CD42b, or by 0.1 μm filtration to remove EMP. Platelet aggregates induced by normal plasma or high molecular weight vWf (Humate-P) dissociated 50% within 15-25 min following 1:20 dilution. In contrast, aggregates formed with EMP persisted two- to threefold longer with the same treatment, indicating greater stability. A similar degree of prolongation of dissociation was observed using plasma from thrombotic thrombocytopenic purpura (TTP) patients compared with normal plasma. Addition of EMP to plasma from severe von Willebrand disease restored his ristocetin-induced platelet aggregation. Multimer analysis of vWf on EMP showed unusually large vWf (ULvWf). In summary, EMP carries ULvWf multimers, promote platelet aggregates, and increase the stability of the aggregates thus formed.

Original languageEnglish (US)
Pages (from-to)1301-1308
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume3
Issue number6
DOIs
StatePublished - 2005

Keywords

  • Endothelial microparticles
  • platelet aggregates
  • thrombotic thrombocytopenic purpura
  • von willebrand disease
  • von willebrand factor

ASJC Scopus subject areas

  • Medicine(all)

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