Perioperative platelet reactivity over time in patients undergoing vascular surgery: An observational pilot study

PLoS One. 2024 Jun 26;19(6):e0304800. doi: 10.1371/journal.pone.0304800. eCollection 2024.

Abstract

Background: Despite Antiplatelet therapy (APT), cardiovascular patients undergoing revascularisation remain at high risk for thrombotic events. Individual response to APT varies substantially, resulting in insufficient protection from thrombotic events due to high on-treatment platelet reactivity (HTPR) in ≤40% of patients. Individual variation in platelet response impairs APT guidance on a single patient level. Unfortunately, little is known about individual platelet response to APT over time, timing for accurate residual platelet reactivity measurement, or the optimal test to monitor residual platelet reactivity.

Aims: To investigate residual platelet reactivity variability over time in individual patients undergoing carotid endarterectomy (CEA) treated with clopidogrel.

Methods: Platelet reactivity was determined in patients undergoing CEA in a prospective, single-centre, observational study using the VerifyNow (change in turbidity from ADP-induced binding to fibrinogen-coated beads), the VASP assay (quantification of phosphorylation of vasodilator-stimulated phosphoprotein), and a flow-cytometry-based assay (PACT) at four perioperative time points. Genotyping identified slow (CYP2C19*2 and CYP2C19*3) and fast (CYP2C19*17) metabolisers.

Results: Between December 2017 and November 2019, 50 patients undergoing CEA were included. Platelet reactivity measured with the VerifyNow (p = < .001) and VASP (p = .029) changed over time, while the PACT did not. The VerifyNow identified patients changing HTRP status after surgery. The VASP identified patients changing HTPR status after eight weeks (p = .018). CYP2C19 genotyping identified 13 slow metabolisers.

Conclusion: In patients undergoing CEA, perioperative platelet reactivity measurements fluctuate over time with little agreement between platelet reactivity assays. Consequently, HTPR status of individual patients measured with the VerifyNow and VASP assay changed over time. Therefore, generally used perioperative platelet reactivity measurements seem unreliable for adjusting perioperative APT strategy.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Platelets* / metabolism
  • Cell Adhesion Molecules / blood
  • Cell Adhesion Molecules / metabolism
  • Clopidogrel* / therapeutic use
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 CYP2C19 / metabolism
  • Endarterectomy, Carotid*
  • Female
  • Humans
  • Male
  • Microfilament Proteins / blood
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Perioperative Period
  • Pilot Projects
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors* / pharmacology
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Platelet Function Tests / methods
  • Prospective Studies
  • Vascular Surgical Procedures

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • CYP2C19 protein, human
  • Cell Adhesion Molecules
  • Microfilament Proteins

Grants and funding

The author(s) received no specific funding for this work.