Microparticle-mediated thrombin generation assay: Increased activity in patients with recurrent thrombosis

L. Bidot, Wenche Jy, C. Bidot, Joaquin J Jimenez, V. Fontana, L. L. Horstman, Yeon Ahn

Research output: Contribution to journalArticle

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Abstract

Background: Circulating cell-derived microparticles (MP) are important players in thrombogenesis, attributed in part to tissue factor (TF) carried on them. We developed MP-mediated thrombin generation assay (TGA) and measured a series of patients with thrombosis (TBS) and normal controls (NC). Methods: MP were isolated from plasma of 66 patients with TBS and 34 NC. The MP were resuspended in normal pooled particle-free plasma (PFP) containing corn trypsin inhibitor (to inhibit contact pathway). MP mediated TGA yields three parameters: lag time, peak and rate. This method is not influenced by anticoagulant therapy. Of the TBS patients, 41 had only a single thrombosis (S-TBS) and 25 had recurrences (R-TBS) within a 5-year period. In parallel, MP were quantitated by flow cytometry, and cell origin was determined: endothelial cells (EMP), leukocytes (LMP), red cells (RMP) and platelets (PMP). Results: MP fromall TBS patients exhibited higher thrombin generation than NC by all three TGA parameters. R-TBS had significantly greater TGA values than S-TBS, reflected in higher peak and rate, and shorter lag time. MP numbers were also higher in TBS vs. NC, for all MP subtypes, and were significantly higher in R-TBS than S-TBS (except LMP). All MP levels correlated with thrombin generation (P < 0.0001), most closely between PMP and peak (R = 0.47) and rate (R = 0.43). Conclusions: MP-mediated TGA is a novel way to assess functional procoagulant activity of MP. Enhanced MP-mediated TGA was demonstrated in TBS patients, and significantly higher activity in R-TBS. These findings support a major role of MP in thrombogenesis.

Original languageEnglish
Pages (from-to)913-919
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number6
DOIs
StatePublished - Jun 1 2008

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Thrombin
Thrombosis
Cell-Derived Microparticles
Thromboplastin
Anticoagulants
Flow Cytometry
Leukocytes
Blood Platelets
Endothelial Cells
Recurrence

Keywords

  • EMP
  • Microparticles
  • PMP
  • Thrombin generation
  • Thrombosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Microparticle-mediated thrombin generation assay : Increased activity in patients with recurrent thrombosis. / Bidot, L.; Jy, Wenche; Bidot, C.; Jimenez, Joaquin J; Fontana, V.; Horstman, L. L.; Ahn, Yeon.

In: Journal of Thrombosis and Haemostasis, Vol. 6, No. 6, 01.06.2008, p. 913-919.

Research output: Contribution to journalArticle

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AU - Bidot, C.

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AU - Fontana, V.

AU - Horstman, L. L.

AU - Ahn, Yeon

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