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Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Expression Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2001, Vol. 98, No. 12, pp. 3340-3345 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Blockade of adenosine diphosphate receptors P2Y12 and P2Y1 is required to inhibit platelet aggregation in whole blood under flow Nancy A. Turner, Joel L. Moake, and Larry V. McIntire From the Department of Bioengineering, Rice University, and the Division of Hematology/Oncology, Baylor College of Medicine, Houston, TX. Using heparinized whole blood and flow conditions, it was shown that adenosine 5'-diphosphate (ADP) receptors P2Y12 and P2Y1 are both important in direct shear-induced platelet aggregation and platelet aggregation subsequent to initial adhesion onto von Willebrand factor (vWf)-collagen. In the viscometer, whole blood was subjected to shear rates of 750, 1500, and 3000 s1 for 30 seconds at room temperature. The extent of aggregation was determined by flow cytometry. The P2Y12 antagonist AR-C69 931MX (ARMX) reduced shear-induced aggregation at these rates by 56%, 54%, and 16%, respectively, compared to control samples. Adenosine 3',5'-diphosphate (A3P5P; P2Y1 antagonist) inhibited shear-induced aggregation by 40%, 30% and 29%, respectively, compared to control samples. Blockade of both ADP receptors at 3000 s1 with ARMX plus A3P5P further reduced the platelet aggregation by 41% compared to the addition of ARMX alone (57% compared to control samples). Using a parallel-plate flow chamber, whole blood was perfused over bovine collagen type 1 at a wall shear rate of 3000 s1 for 60 seconds. Platelet deposition was quantified with epifluorescence video microscopy and digital image processing. Blockade of P2Y12 alone or blockade of P2Y1 alone did not reduce thrombus formation on vWf-collagen. In contrast, blockade of both P2Y12 and P2Y1 reduced platelet deposition by 72%. These results indicate that combinations of antagonists of the ADP receptors P2Y12 and P2Y1 are effective inhibitors of direct shear-induced platelet aggregation and of platelet aggregation subsequent to initial adhesion under flow conditions. Inhibitors of these pathways are potentially useful as antiarterial thrombotic agents. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Effects of adenosine 5'-diphosphate (ADP) receptor blockade on platelet aggregation under flow Shinya Goto, Noriko Tamura, Shunnosuke Handa, Nancy A.Turner, Joel L. Moake, and Larry V. McIntire Blood 2002 99: 4644-4646. [Full Text] [PDF] This article has been cited by other articles: Y. Jiang, L. Borrelli, B. J. 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