Fab-mediated binding of drug-dependent antibodies to platelets in quinidine- and quinine-induced thrombocytopenia.
Citations
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Cites background from "Fab-mediated binding of drug-depend..."
...In 1985, Aster's group showed that antibodies from patients with quinine and quinidine-induced thrombocytopenia bound to the platelets by their Fab portion, not their Fc portion, of the Ig molecule.(36) This did not support the “nonspecific” adsorption of drug–anti-drug complexes as suggested by Shulman, and even later suggestions that the attachment was to the Fc receptor on platelets....
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186 citations
References
198 citations
"Fab-mediated binding of drug-depend..." refers methods in this paper
...6 mMEDTA) by differential centrifugation as previously described (7)....
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186 citations
"Fab-mediated binding of drug-depend..." refers background in this paper
...Ackroyd (13) proposed a mechanism for the drug-ddAbplatelet reaction in which drug, acting as a hapten, modified a platelet constituent to produce a hapten-carrier complex which induces antibody formation....
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153 citations
"Fab-mediated binding of drug-depend..." refers background in this paper
...Drugs like quinidine and quinine bind weakly to platelets in the absence of ddAb (2, 3); excess soluble drug is required for maximum ddAb binding to platelets (3); and excess soluble drug fails to displace platelet-bound ddAb (2, 3), but it is not yet certain whether ddAb interact with platelets via the Fab or the Fc portion of the antibody molecule....
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...Shulman (2) provided experimental support for the latter hypothesis by showing that quinidine binds only weakly to platelets and would, therefore, be unlikely to form complexes capable of inducing antibody, and that high concentrations of drug do not displace plateletbound ddAb, as would be expected in a conventional hapten inhibition reaction....
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125 citations
"Fab-mediated binding of drug-depend..." refers background in this paper
...It is unlikely that this apparent platelet-platelet binding was due to aggregation, since it occurred in the presence of 8 mMEDTA and, in some experiments, 20 ng/ ml PGEI, which is a potent inhibitor of aggregation (10)....
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65 citations
"Fab-mediated binding of drug-depend..." refers background or methods in this paper
...These observations seem most consistent with the following model for drug-ddAb-platelet binding: platelets coated with drug express an unstable neoantigen which is stabilized upon interaction with the Fab domains of ddAb (3)....
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...Drugs like quinidine and quinine bind weakly to platelets in the absence of ddAb (2, 3); excess soluble drug is required for maximum ddAb binding to platelets (3); and excess soluble drug fails to displace platelet-bound ddAb (2, 3), but it is not yet certain whether ddAb interact with platelets via the Fab or the Fc portion of the antibody molecule....
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...Weconfirmed and extended these observations by showing that even platelets coated with a million molecules of drug do not express ddAb binding sites unless excess soluble drug is present (3)....
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...That is, platelets pretreated with drug and then washed do not express binding sites for ddAb, and bound ddAb can readily be removed from platelets by washing in the absence of drug (3)....
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...Mixtures were then centrifuged at 12,800 g for 2 min, and supernatants were analyzed for IgG content by electroimmunoassay (3)....
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