title: On the Use of the Platelet Activity State Assay for the In Vitro Quantification of Platelet Activation in Blood Recirculating Devices for Extracorporeal Circulation.
abstract: We designed an experimental setup to characterize the thrombogenic potential associated with blood recirculating devices (BRDs) used in extracorporeal circulation (ECC). Our methodology relies on in vitro flow loop platelet recirculation experiments combined with the modified-prothrombinase platelet activity state (PAS) assay to quantify the bulk thrombin production rate of circulated platelets, which correlates to the platelet activation (PA) level. The method was applied to a commercial neonatal hollow fiber membrane oxygenator. In analogous hemodynamic environment, we compared the PA level resulting from multiple passes of platelets within devices provided with phosphorylcholine (PC)-coated and noncoated (NC) fibers to account for flow-related mechanical factors (i.e., fluid-induced shear stress) together with surface contact activation phenomena. We report for the first time that PAS assay is not significantly sensitive to the effect of material coating under clinically pertinent flow conditions (500 mL/min), while providing straightforward information on shear-mediated PA dynamics in ECC devices. Being that the latter is intimately dependent on local flow dynamics, according to our results, the rate of thrombin production as measured by the PAS assay is a valuable biochemical marker of the selective contribution of PA in BRDs induced by device design features. Thus, we recommend the use of PAS assay as a means of evaluating the effect of modification of specific device geometrical features and/or different design solutions for developing ECC devices providing flow conditions with reduced thrombogenic impact.
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy. filippo.consolo@polimi.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Consolo
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Valerio
authors.affiliation: Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Facoltà di Medicina Veterinaria, Università di Milano, Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Brizzola
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rota
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Marazzato
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vincoli
authors.affiliation: Sorin Group Italia, Mirandola, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Reggiani
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Redaelli
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Fiore
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D004867:Equipment Design; D005112:Extracorporeal Circulation / Q000009:adverse effects / Q000295:instrumentation*; D006801:Humans; D015539:Platelet Activation; D010979:Platelet Function Tests / Q000379:methods; D012756:Sheep; D013314:Stress, Mechanical; D013927:Thrombosis / Q000209:etiology
keywords: Blood recirculating devices; Extracorporeal circulation; Platelet activation; Shear- and contact-associated thrombogenicity