Testing platelet activation with a shear-dependent platelet function test versus aggregation-based tests: relevance for monitoring long-term glycoprotein IIb/IIIa inhibition

Circulation. 2001 Mar 20;103(11):1488-91. doi: 10.1161/01.cir.103.11.1488.

Abstract

Background: Tests developed to monitor glycoprotein (GP) IIb/IIIa blockade do not properly reflect platelet function in vivo and need a baseline (pretreatment) value. Because GP IIb/IIIa is essential in platelet aggregation and thrombosis under shear conditions, a flow-dependent approach to monitor its inhibition can be used.

Methods and results: We compared a test based on flow-dependent platelet deposition, the Cone and Platelet Analyzer (CPA), with in vitro platelet aggregometry and the Rapid Platelet Function Assay (RPFA) on platelet function after GP IIb/IIIa inhibition. In vitro, increasing concentrations of abciximab (0% to 100% receptor occupancy) were tested. Ex vivo, platelet function was monitored with the CPA and with aggregometry for up to 1 week after abciximab administration. The CPA was better correlated with the percentage of free GP IIb/IIIa receptors than was aggregometry or the RPFA. Only the RPFA, when expressed as a ratio over baseline (pretreatment), was comparable to the CPA. Ex vivo, the CPA, but not aggregometry, showed prolonged platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade in the first week after abciximab administration.

Conclusions: Platelet function assessment by shear-induced deposition is a reliable test to monitor a wide range of GP IIb/IIIa inhibition. Its accuracy does not require a baseline reference. The effects of GP IIb/IIIa blockade on platelet function should be examined under high shear conditions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abciximab
  • Antibodies, Monoclonal / pharmacology
  • CD36 Antigens / metabolism*
  • Humans
  • Immunoglobulin Fab Fragments / pharmacology
  • In Vitro Techniques
  • Platelet Activation / drug effects
  • Platelet Activation / physiology*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / physiology*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Function Tests / methods
  • Platelet Glycoprotein GPIb-IX Complex / antagonists & inhibitors
  • Platelet Glycoprotein GPIb-IX Complex / metabolism*

Substances

  • Antibodies, Monoclonal
  • CD36 Antigens
  • Immunoglobulin Fab Fragments
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIb-IX Complex
  • Abciximab