A novel automated microchip flow-chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions

K. Hosokawa, T. Ohnishi, T. Kondo, M. Fukasawa, T. Koide, I. Maruyama, K. A. Tanaka

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

Background and aims:In the present study, we describe a newly developed microchip-based analytical system to evaluate white thrombus formation (WTF). Efficacies of various antithrombotic agents were compared under different flow conditions. Methods:Whole blood containing corn trypsin inhibitor was perfused over a microchip coated with collagen and tissue thromboplastin at the lower and higher shear rates of 240 and 600s -1, and WTF process inside the microchip was quantified by monitoring a flow pressure. Parameters of T 10 (time to 10kPa), T 10-80 (time from 10 to 80kPa) and OT (occlusion time; time to 80kPa) were used to evaluate the onset and the growth rate of WTF, and the capillary occlusion, respectively. Results:After perfusion was started, white thrombus composed of activated platelets and fibrin was formed on the coated surface. Thrombus gradually increased in size and eventually occluded the capillary. Among anticoagulants, heparin (0.5-1.0UmL -1) potently prolonged T 10 at both shear rates, whereas low molecular weight heparin (1.0-2.0IUmL -1) inhibited the growth of WTF at the lower shear rate. Among antiplatelet agents, abciximab (1-2μgmL -1) significantly reduced the size and number of thrombi, which was additively enhanced in the presence of heparin (0.5UmL -1). OS-1 (specific GPIbα-antagonist) prevented the complete capillary occlusion. Conclusion:The novel monitoring system of WTF may be useful in preclinical and clinical evaluations of different types of antithrombotic strategies, and their effects in combination.

Original languageEnglish
Pages (from-to)2029-2037
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume9
Issue number10
DOIs
Publication statusPublished - 2011 Oct 1

Keywords

  • Coagulation
  • Microchip flow-chamber
  • Platelet activation
  • Shear rate
  • Thrombus formation

ASJC Scopus subject areas

  • Hematology

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