Role of VASP Phosphorylation Assay in Monitoring the Antiplatelet Therapy

Open access


Dual antiplatelet treatment with clopidogrel and aspirin represents standard regimen in prevention of thromboembolic events in patients with ischemic heart disease undergoing percutaneous coronary intervention (PCI). One of the greatest pitfalls of clopidogrel treatment is large inter-individual variability in response. Large amount of patients does not respond adequately and therefore are not „protected“ even in spite of receiving the therapy. Poor responders are exposed to three-fold increased risk of myocardial infarction, stent thrombosis and cardiac death.

Clopidogrel is an antiplatelet prodrug, whose active metabolite inhibits platelet function by irreversible binding to the (adenosine diphosphate) platelet receptor P2Y12. Receptor P2Y12 plays primal role in ADP-mediated platelet activation, and also in mechanism of action of ADP inhibitors such as clopidogrel, prasugrel etc. Reasons stated above, raised the necessity for implementing reliable laboratory test in order to identify the unprotected patients. In an ideal scenario, such test would serve to adjust the dose and guide the individual tailored treatment.

Vasodilator Stimulated Phosphoprotein (VASP) is an intracellular platelet protein which is non phosphorylated at basal state. Since its relation in cascade with P2Y12 receptor, VASP phosphorylation corerlates with inhibition of P2Y12 which is the receptor of prime importance in ADP mediated activation of platelets and as is primary target of ADP inhibitors action. Outcome of the assay is represented as the value of platelet reactivity index (PRI), where PRI values above 50% are considered inadequate response to treatment and signal exposure to increased risk of myocardial infarction, post-PCI stent thrombosis and cardiac death. VASP-P flow cytometric assay is emerging into the spotlight as the promising method, mostly for its specificity for ADP inhibitors, better outlook for standardising results and lesser sample manipulation compared to multiple electrode aggregometry.

  • 1. O’Connor S, Montalescot G, Collet JP. The P2Y12 receptor as a target of antithrombotic drugs. Purinergic Signalling 2011; 7: 325-332.

  • 2. Cattaneo M. , Aspirin and Clopidogrel : Efficacy, Safety, and the Issue of Drug ResistanceArteriosclerosis, Thrombosis, and Vascular Biology. 2004; 24: 1980-1987)

  • 3. Montalescot G, Wiviott SD, Braunwald E, et al for the TRITON-TIMI 38 investigators. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009; 373: 723-731

  • 4. Bonaca MP, Steg PG, Feldman L, Canales JF, Ferguson J, Wallentin L, Califf RM, et al. Antithrombotics in Acute Coronary Syndromes. J Am Coll Cardiol 2009; 54, 11: 969- 984.

  • 5. Cattaneo M. Response variability to clopidogrel: is tailored treatment, based on laboratory testing, the right solution? J Thromb Haemost 2012; 10: 327-36.

  • 6. Wang X, Zhang D, Zhuang S, Lai Y. Modifying Clopidogrel Maintenance Doses According to Vasodilator- Stimulated Phosphoprotein Phosphorylation Index Improves Clinical Outcome in PatientsWith Clopidogrel Resistance. Clin Cardiol 2011; 34, 5, 332-338.

  • 7. Wallentin L, et al. P2Y12 inhibitors : differences in properties and mechanisms of action and potential consequences for clinical use. European Heart Journal 2009; 30, 1964-1977.

  • 8. Buonamici P, Marcucci R, Migliorini A, et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol 2007; 49: 2312-7.

  • 9. Gachet C, B.Aleil B, Testing antiplatelet therapy. European Heart Journal Supplements 2008; 10 (Suppl A), A28-A34.

  • 10. Aleil B, Ravanat C, Cazenave JP, Rochoux G, Heitz A, Gachet C. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases. J Thromb Haemost 2005; 3: 85-92.

  • 11. STAGO - Biocytex ® (France), Manual for PLT VASP/P2Y12 kit; user_upload/Biocytex/7014-english.pdf

  • 12. Bonello L, Camoin-Jau L, Armero S, et al. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis. Am J Cardiol. 2009;103:5-10.

Acta Medica Martiniana

The Journal of Comenius University in Bratislava

Journal Information


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 14 14 14
PDF Downloads 2 2 2