Vasodilator-stimulated phosphoprotein (VASP) is a ubiquitous vertebrate intracellular protein that becomes activated via phosphorylation. Once phosphorylated, VASP triggers cell motility through its interaction with the contratile protein actin. In platelets, VASP generates pseudopod formation during platelet activation. VASP becomes phosphorylated (VASP-P) when ADP binds its platelet membrane receptor site, P2Y12. Activation requires prostaglandin E1 and functions through the cyclic AMP “second messenger” system.
VASP-P may be exploited as a marker for ADP-induced platelet activation. It is not activated by ADP‘s binding to its alternate receptor, P2Y1 nor is VASP phosphorylated by other agonists. Further, the P2Y12 receptor antagonists clopidogrel, prasugrel, cangrelor, and ticagrelor suppress VASP-P formation, thus VASP-P may also be used to detect ADP receptor antagonist low responders (resistant), who may suffer increased risk for venous and arterial thrombosis. Intracellular VASP-P concentration is measured using a monoclonal fluorophor or chromophore-tagged VASP-P-specific antibody and quantitatid via enzyme immunoassay or flow cytometry. The results are reported as platelet reactivity index % (PRI%), which is inversely proportional to VASP-P activation. Patients who are receiving one of the P2Y12 receptor antagonist but whose PRI% exceeds an established limit are classified as low responders.
Because of its analytical specificity and sensitivity, the VASP-P assay compares favorably with current platelet function assays, including light transmittance aggregometry and the Accriva VerifyNow P2Y12 assay, when detecting P2Y12 antagonist low responders. Here are a few references that compare VASP-P correlation to current platelet function assay:
- Bonello L, Laine M, Baumstarck K, et al. A randomized trial of platelet reactivity monitoring-adjusted clopidlgrel therapy versus prasugrel therapy to reduce high in-treatment platelet reactivity. Int J Cardiol 2013;;168:4244–8.
- Braun O, Angiolillo DJ, Ferreiro JL, et al. Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways. Thromb Haemost 2013;110:1223–31.
- Cuisset T, Grosdidier C, Loundou AD, et al. Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleeding with antiplatelet drugs). JACC Cardiovasc Interv 2013;6:854–63.
- Delavenne X, Magnin M, Basset T, et al. Investigation of drug-drug interactions between clopidogrel and fluoxetine. Fundam Clin Pharmacol 2013;27:683–9.
- Erlinge D, Gurbel PA, James S, et al. Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol 2013;62:577–83.