title: A novel automated microchip flow-chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions.
abstract: OBJECTIVE
  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 600 s(-1) , and WTF process inside the microchip was quantified by monitoring a flow pressure. Parameters of T(10) (time to 10 kPa), T(10-80) (time from 10 to 80 kPa) and OT (occlusion time; time to 80 kPa) 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 (0.5-1.0 U mL(-1)) potently prolonged T(10) at both shear rates, whereas low molecular weight heparin (1.0-2.0 IU mL(-1)) inhibited the growth of WTF at the lower shear rate. Among antiplatelet agents, abciximab (1-2 μg mL(-1)) significantly reduced the size and number of thrombi, which was additively enhanced in the presence of heparin (0.5 U mL(-1) ). OS-1 (specific GPIbα-antagonist) prevented the complete capillary occlusion.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Institute, Fujimori Kogyo Co., Yokohama, Kanagawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hosokawa
authors.forename: T
authors.initials: T
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: M
authors.initials: M
authors.lastname: Fukasawa
authors.forename: T
authors.initials: T
authors.lastname: Koide
authors.forename: I
authors.initials: I
authors.lastname: Maruyama
authors.forename: K A
authors.initials: KA
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D001331:Automation; D001775:Blood Circulation; D015153:Blotting, Western; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013927:Thrombosis / Q000503:physiopathology*
chemical_list: D010975:Platelet Aggregation Inhibitors