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 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.
Lepäntalo
A
A
Wihuri Research Institute, Kalliolinnantie 4, Fin-00140 Helsinki, Finland.
Beer
J H
JH
Siljander
P
P
Syrjälä
M
M
Lassila
R
R
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D019343:Citric Acid / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D016023:Integrins / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests / Q000295:instrumentation*; D011110:Polymorphism, Genetic; D038981:Receptors, Collagen; D015203:Reproducibility of Results; D012212:Rheology; D013314:Stress, Mechanical
D000590:Amino Acid Chloromethyl Ketones; D000925:Anticoagulants; D016023:Integrins; D038981:Receptors, Collagen; D019343:Citric Acid; D000244:Adenosine Diphosphate; D003094:Collagen; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone; D004837:Epinephrine