Variability in platelet responses to collagen--comparison between whole blood perfusions, traditional platelet function tests and PFA-100

Thromb Res. 2001 Jul 15;103(2):123-33. doi: 10.1016/s0049-3848(01)00283-3.

Abstract

The purpose of this study was to determine if the results obtained in platelet function tests and whole blood perfusions are associated with those in platelet function analyser (PFA)-100. We used collagen type I monomers and fibrils to analyse the distinct roles of glycoprotein (GP) Ia/IIa and other collagen receptors in flowing blood under a high shear rate (1600/s) and in aggregation studies. Also, anticoagulation [citrate vs. D-phenylalanyl-1-prolyl-1 arginine chloromethyl ketone (PPACK)] was varied to enhance the functions of GP Ia/IIa, since it has been shown that the cation-poor environment of citrated blood impairs GP Ia/IIa-dependent platelet recruitment. Large interindividual variability (45-fold) was detected in deposition of platelets in whole blood perfusions over collagen monomers, whereas this variation was only fourfold in fibrils. In PFA, this variation was reduced to 2.5-fold. However, platelet deposition on monomers is associated with epinephrine-enhanced PFA (r=-.49, P<.03), whereas platelet deposition on fibrils is correlated with adenosine diphosphate (ADP)-enhanced PFA (r=-.47, P<.05), suggesting a distinct synergism between epinephrine and monomers (GP Ia/IIa) as well as ADP with fibrils (other collagen receptors). Donors with 807 C/C polymorphism of GP Ia (n=14) had longer lag phase in aggregation experiments compared with C/T (n=7) both by monomers and fibrils (P<.04), but these polymorphisms with their mild impact on GP Ia/IIa activity did not markedly differ in other tests. In conclusion, the results obtained in perfusion studies and PFA experiments correlated, but PFA fails to reveal the large-scale variability related to collagen-induced platelet responses.

Publication types

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

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adult
  • Aged
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Anticoagulants / pharmacology
  • Blood Platelets / drug effects*
  • Citric Acid / pharmacology
  • Collagen / chemistry
  • Collagen / pharmacology*
  • Drug Synergism
  • Epinephrine / pharmacology
  • Female
  • Genetic Variation
  • Humans
  • Integrins / drug effects
  • Integrins / physiology
  • Male
  • Middle Aged
  • Perfusion
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects*
  • Platelet Function Tests / instrumentation*
  • Polymorphism, Genetic
  • Receptors, Collagen
  • Reproducibility of Results
  • Rheology
  • Stress, Mechanical

Substances

  • Amino Acid Chloromethyl Ketones
  • Anticoagulants
  • Integrins
  • Receptors, Collagen
  • Citric Acid
  • Adenosine Diphosphate
  • Collagen
  • phenylalanyl-prolyl-arginine-chloromethyl ketone
  • Epinephrine