Polymorphisms of glycoprotein Ib affect the inhibition by aurintricarboxylic acid of the von Willebrand factor dependent platelet aggregation.
Two polymorphisms of platelet glycoprotein Ib, VNTR and Thr/Met(145), regarded as the possible inherited risks factors for thromboembolic complications, have been suggested to underlie platelet response to activating stimuli. This study examined the functional significance of these polymorphisms in platelet reactivity and sensitivity to aurintricarboxylic acid (the antagonist of von Willebrand factor, vWF). To evaluate platelet function at low and high flow conditions we monitored the ristocetin-induced and vWF-mediated aggregation of isolated platelets and the platelet function analyzer collagen/ADP closure time (PFA-100 CT(CADP)), which reflects platelets' ability to adhere and aggregate in whole blood. Aurintricarboxylic acid significantly reduced ristocetin-induced platelet agglutination in a dose-dependent manner (IC(50)=3.5+/-1.9 microM). At the concentration of 100 microM it also markedly prolonged PFA-100 CT(CADP) (up to 147+/-32 s vs. 94+/-17 s in control). The efficacy of this antagonist in the inhibition of vWF-mediated platelet agglutination was approximately 1.5-fold higher in the VNTR B/Met145(+) carriers than in VNTR B/Met145(-) carriers ( P<0.05). Otherwise, no significant differences occurred between VNTR B/Met(145)-positive and B/Met(145)-negative individuals in the prolongation of closure time by ATA. These findings indicate that under certain experimental conditions VNTR-B and Met(145) alleles may contribute to the increased platelet sensitivity to some antagonists of platelet natural ligands.
Boncler
M A
MA
Laboratory of Hemostasis and Hemostatic Disorders, Medical University of Lodz, ul. Narutowicza 96, 90-141 Lodz, Poland.
Golanski
J
J
Paczuski
R
R
Watala
C
C
D000328:Adult; D000483:Alleles; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010974:Platelet Aggregation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D012310:Ristocetin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D008024:Ligands; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D012310:Ristocetin; D001312:Aurintricarboxylic Acid