28.06 Nitric oxide in extracorporeal circulation preserves platelet function as measured by microparticles

T. R. Bellomo1, M. Jeakle1, T. Major1, M. Meyerhoff2, R. H. Bartlett1  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA 2University Of Michigan,Department Of Chemistry,Ann Arbor, MI, USA

Background: Clotting, anticoagulation, platelet consumption, and poor platelet function are major factors in clinical extracorporeal circulation (ECC). We have shown that Nitric Oxide releasing coatings (NOReL) prevents thrombosis in a rabbit model of ECC without systemic anticoagulation. NOReL prevents platelet adhesion and activation, resulting in preserved platelet count and function. Previous work has shown that activated platelets form platelet-derived microparticles (PMPs). These experiments were designed to determine if PMPs can identify platelet function during ECC.

Objective: The objective of this study is to investigate the effects of NOReL on platelet activation and PMP formation during ECC.

Methods: Uncoated and NOReL coated ECCs were tested in a 4-hour rabbit thrombogenicity model without systemic anticoagulation. Before and after ECC exposure, platelets were stimulated with collagen and PMPs were measured using flow cytometry. 

Results: The uncoated ECCs clotted within the first hour, while the NOReL coated ECCs circulated for 4 hours. Pre ECC exposure, platelets stimulated with collagen produced PMPs. Post ECC exposure, platelets from uncoated circuits generated less PMPs than baseline (186 ± 123 uncoated baseline vs.-131 ± 311 uncoated post circuit) when stimulated with collagen.  However, platelets from the NOReL circuit generated the same amount of PMPs as baseline values (74 ± 61 NOReL baseline vs. 56 ± 118 NOReL post circuit).

Conclusions: Blood exposure during ECC results in platelet activation and clotting. The remaining circulating platelets have lost function, as demonstrated by the low PMP formation in response to collagen. NOReL coated ECCs prevent platelet activation and clotting. In addition, function of the circulating platelets was preserved, as demonstrated by PMP formation in response to collagen. These results indicate that PMPs may be an important measure of platelet activation during ECC. PMPs may provide a simplified way to measure platelet function during clinical ECC.