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

The purpose of this study was to determine if the results obtained in plate let 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 i n aggregation studies. Also, anticoagulation [citrate VS. D-phenylalanyl-1- prolyl-1 arginine chloromethyl ketone (PPACK)] was varied to enhance the fu nctions of GP Ia/IIa, since it has been shown that the cation-poor environm ent of citrated blood impairs GP Ia/IIa-dependent platelet recruitment. Lar ge interindividual variability (45-fold) was detected in deposition of plat elets in whole blood perfusions over collagen monomers, whereas this variat ion was only fourfold in fibrils. In PFA, this variation was reduced to 2.5 -fold. However, platelet deposition on monomers is associated with epinephr ine-enhanced PFA (r = -.49, P < .03), whereas platelet deposition on fibril s is correlated with adenosine diphosphate (ADP)-enhanced PFA (r = -.47, P < .05), suggesting a distinct synergism between epinephrine and monomers (G P Ia/IIa) as well as ADP with fibrils (other collagen receptors). Donors wi th 807 C/C polymorphism of GP Ia (n = 14) had longer lag phase in aggregati on 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 reve al the large-scale variability related to collagen-induced platelet respons es. (C) 2001 Elsevier Science Ltd. All rights reserved.