Assessment of platelet aggregation responses in vivo in the mouse

Abstract

Platelet aggregation responses are conventionally assessed in cuvette-based systems using either isolated platelets or whole blood. Unfortunately, in vitro aggregometry poorly predicts in vivo functionality, since mediators derived from the vascular endothelium are major regulators of platelet function. There is a need, therefore, for functional assays that assess platelet responsiveness in vivo in the presence of an intact and functional vascular endothelium. We have developed methodology for monitoring aggregation responses of freely circulating radiolabelled platelets using external detection probes in the anaesthetised mouse. Intravenous injection of platelet agonists induces reversible, dose-dependent aggregation responses that are sensitive to anti-platelet therapies and modification of the vascular endothelium. The technique provides a means of determining the effects of pharmacological and genetic manipulation upon platelet function in vivo.