P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditions.

P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditionsw

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Blockade of adenosine diphosphate receptors P2Y12 and P2Y1 is required to inhibit platelet aggregation in whole blood under flow

Using heparinized whole blood and flow conditions, it was shown that adenosine 5*-diphosphate (ADP) receptors P2Y12 and P2Y1 are both important in direct shearinduced 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 s21 for 30 seconds at room...

Contact activation of blood coagulation on a defined kaolin/collagen surface in a microfluidic assay.

Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm(2))/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor, corn trypsin inhibitor) drove platelet deposi...

Detection of platelet sensitivity to inhibitors of COX-1, P2Y₁, and P2Y₁₂ using a whole blood microfluidic flow assay.

BACKGROUND Microfluidic devices recreate the hemodynamic conditions of thrombosis. METHODS Whole blood inhibited with PPACK was treated ex vivo with inhibitors and perfused over collagen for 300 s (wall shear rate=200 s(-1)) using a microfluidic flow assay. Platelet accumulation was measured in the presence of COX-1 inhibitor (aspirin, ASA), P2Y₁ inhibitor (MRS 2179), P2Y₁₂ inhibitor (2MeSAMP...

PLATELETS AND THROMBOPOIESIS Multiscale prediction of patient-specific platelet function under flow

During thrombotic or hemostatic episodes, platelets bind collagen and release ADP and thromboxane A2, recruiting additional platelets to a growing deposit that distorts the flow field. Prediction of clotting function under hemodynamic conditions for a patient’s platelet phenotype remains a challenge. A platelet signaling phenotype was obtained for 3 healthy donors using pairwise agonist scannin...