Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood

G. L. Mendolicchio, D. Zavalloni, M. Bacci, E. Corrada, M. Marconi, C. Lodigiani, P. Presbitero, L. Rota, Z. M. Ruggeri

Research output: Contribution to journalArticle

Abstract

Background and objectives: Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. Methods and results: We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500s-1. The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. Conclusions: Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.

Original languageEnglish
Pages (from-to)373-382
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Thrombosis
Blood Platelets
clopidogrel
Aspirin
Perfusion
Fibrillar Collagens
Purinergic P2 Receptors
Ticlopidine
Video Microscopy
Normal Distribution
Percutaneous Coronary Intervention
Collagen Type I
Collagen
Therapeutics
Phosphorylation

Keywords

  • Aspirin
  • Platelet receptor blockers
  • Thienopyridines
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood. / Mendolicchio, G. L.; Zavalloni, D.; Bacci, M.; Corrada, E.; Marconi, M.; Lodigiani, C.; Presbitero, P.; Rota, L.; Ruggeri, Z. M.

In: Journal of Thrombosis and Haemostasis, Vol. 9, No. 2, 02.2011, p. 373-382.

Research output: Contribution to journalArticle

Mendolicchio, G. L. ; Zavalloni, D. ; Bacci, M. ; Corrada, E. ; Marconi, M. ; Lodigiani, C. ; Presbitero, P. ; Rota, L. ; Ruggeri, Z. M. / Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood. In: Journal of Thrombosis and Haemostasis. 2011 ; Vol. 9, No. 2. pp. 373-382.
@article{7b03df2f02f64e2597889c7a4d111d95,
title = "Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood",
abstract = "Background and objectives: Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. Methods and results: We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500s-1. The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3{\%} of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6{\%} of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. Conclusions: Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.",
keywords = "Aspirin, Platelet receptor blockers, Thienopyridines, Thrombosis",
author = "Mendolicchio, {G. L.} and D. Zavalloni and M. Bacci and E. Corrada and M. Marconi and C. Lodigiani and P. Presbitero and L. Rota and Ruggeri, {Z. M.}",
year = "2011",
month = "2",
doi = "10.1111/j.1538-7836.2010.04144.x",
language = "English",
volume = "9",
pages = "373--382",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood

AU - Mendolicchio, G. L.

AU - Zavalloni, D.

AU - Bacci, M.

AU - Corrada, E.

AU - Marconi, M.

AU - Lodigiani, C.

AU - Presbitero, P.

AU - Rota, L.

AU - Ruggeri, Z. M.

PY - 2011/2

Y1 - 2011/2

N2 - Background and objectives: Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. Methods and results: We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500s-1. The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. Conclusions: Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.

AB - Background and objectives: Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. Methods and results: We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500s-1. The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. Conclusions: Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.

KW - Aspirin

KW - Platelet receptor blockers

KW - Thienopyridines

KW - Thrombosis

UR - http://www.scopus.com/inward/record.url?scp=79251547404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251547404&partnerID=8YFLogxK

U2 - 10.1111/j.1538-7836.2010.04144.x

DO - 10.1111/j.1538-7836.2010.04144.x

M3 - Article

C2 - 21083646

AN - SCOPUS:79251547404

VL - 9

SP - 373

EP - 382

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 2

ER -