title: Aggregated-disaggregated, refractory platelets retain sensitivity to ristocetin.
abstract: The present investigation has used an aggregation-disaggregation-reaggregation model to determine if exposure to potent aggregating agents causing a refractory state in deaggregated platelets results in down-regulation and clearance of GPIb/IX, the receptor for von willebrand factor. Thrombin, the thrombin receptor activating peptide (TRAP) and the thromboxane A2 mimic, U46619, caused irreversible aggregation and secretion when stirred on an aggregometer with plateletrich plasma (PRP). Addition of prostaglandin E1 (PGE1) after the plateau of maximum aggregation was reached caused rapid dissociation of platelet aggregates. Dissociated platelets were refractory to a second exposure to the primary stimulus or to other aggregating agents. Exposure of the refractory cells to epinephrine before the primary agent restored sensitivity resulting in a second wave of irreversible aggregation. Deaggregated, refractory platelets, however, retained their sensitivity to ristocetin. Amounts of the antibiotic causing agglutination of resting PRP also caused agglutination of disaggregated, refractory platelets. Addition of epinephrine to samples of refractory platelets less sensitive to low concentrations of the antibiotic restored their capacity to undergo irreversible ristocetin-induced agglutination. Analysis of the frequency of gold particles associated with monoclonal antibodies directed against GPIb/IX on control platelets and disaggregated, refractory platelets showed no significant difference in the number of receptors. The findings indicate that significant numbers of GPIb/IX receptors remain on platelet surfaces following exposure to potent aggregating agents.
authors.affiliation: Department of Laboratory Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: White
authors.forename: G H
authors.initials: GH
authors.lastname: Rao
mesh_terms: D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D015536:Down-Regulation; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D012310:Ristocetin / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D012310:Ristocetin; D013917:Thrombin; D000527:Alprostadil; D004837:Epinephrine