Fab-mediated binding of drug-dependent antibodies to platelets in quinidine- and quinine-induced thrombocytopenia.
TLDR
Findings suggest that binding of drug-induced antibodies to platelets occurs at the Fab domains of the IgG molecule.Abstract:
Platelets coated with quinine- or quinidine-induced antibodies form rosettes around protein A-Sepharose beads and normal platelets form rosettes about protein A-Sepharose beads coated with these antibodies. These reactions occurred only in the presence of sensitizing drug. Platelets also formed rosettes about protein A-Sepharose beads coated with an anti-PIA1 antibody, but drug was not required. Formation of rosettes between antibody-coated platelets and protein A-Sepharose was inhibited by F(ab')2 fragments of goat antibody specific for the Fc portion of human IgG, while rosette formation between antibody-coated protein A-Sepharose and platelets was inhibited by F(ab')2 fragments directed against the F(ab')2 portion of the IgG molecule. Since binding of IgG to protein A is known to occur via the Fc region, these findings suggest that binding of drug-induced antibodies to platelets occurs at the Fab domains of the IgG molecule.read more
Citations
More filters
Journal ArticleDOI
Drug-induced thrombocytopenia: localization of the binding site of GPIX-specific quinine-dependent antibodies.
TL;DR: The characterization of the quinine-dependent antibody activity of sera from 13 patients with qu inine-induced thrombocytopenia indicated that replacement of the Arg110 and Gln115 of the human GPIX with the corresponding residues from mouse resulted in a significant reduction in the binding of GPIX antibodies in this series of patients.
Journal ArticleDOI
Can drugs cause autoimmune thrombocytopenic purpura
TL;DR: Clinicians should consider the possibility of an exogenous trigger in patients who present with apparent autoimmune thrombocytopenia, and studies of drug-induced ITP may provide clues to the general mechanisms whereby drugs and other xenobiotics induce immune diseases.
Journal ArticleDOI
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a target glycoprotein in drug-induced thrombocytopenia.
TL;DR: Analysis of 20 sera from patients with quinidine-induced thrombocytopenia by MAIPA assay revealed evidence that DDAbs against PECAM-1 are involved in addition to anti-GPIb/IX and anti-GPIIb/IIIa.
Journal ArticleDOI
Heterogeneity of drug-dependent platelet antigens and their antibodies in quinine- and quinidine-induced thrombocytopenia: involvement of glycoproteins Ib, IIb, IIIa, and IX.
TL;DR: Examination of platelet receptors for quinine- and quinidine- dependent antiplatelet antibodies revealed different populations of antibodies with different specificities within the one patient, indicating Q.Ab and Qd.Ab are heterogeneous and may be directed toward different epitopes on major platelet glycoproteins.
Journal ArticleDOI
An immediate hemolytic reaction induced by repeated administration of oxaliplatin.
Vivien M. Chen,Karen M. Thrift,Marie-Christine Morel-Kopp,David J. Jackson,Chris Ward,Robert L. Flower +5 more
TL;DR: Platinum‐based chemotherapy agents have been associated with potentially fatal acute immune‐mediated hemolytic anemia and the target antigen, cause of the positive direct antiglobulin test (DAT), and mechanism of hemolysis have been the subject of controversy.
References
More filters
Journal ArticleDOI
A platelet and granulocyte membrane defect in paroxysmal nocturnal hemoglobinuria: usefulness for the detection of platelet antibodies
Richard H. Aster,Sara E. Enright +1 more
TL;DR: It is concluded that, in PNH, platelets and granulocytes share the membrane defect characteristic of erythrocytes in this disorder, and these observations support the concept that PNH arises as the result of a somatic mutation in a primitive cell capable of differentiating into ery Throttleblast, myeloblast, and megakaryoblast lines.
Journal ArticleDOI
Allergic purpura, including purpura due to foods, drugs and infections.
TL;DR: Purpura occurring during convalescence can best be explained on the assumption of an allergic basis, similar perhaps to that to which nephritis following streptococcal infections has been attributed.
Journal ArticleDOI
Immunoreactions involving platelets. I. A steric and kinetic model for formation of a complex from a human antibody, quinidine as a haptene, and platelets; and for fixation of complement by the complex.
TL;DR: Results of this study were consistent with the possibilities that the protein moiety of a haptenic antigen involved in development of an antibody which attaches to a cell is not necessarily a component of the cell, and that the cell reacts with the antibody by virtue of having a surface favorable for non-specific adsorption of certain haptene-antibody complexes.
Journal ArticleDOI
Cyclic AMP metabolism in cholesterol-rich platelets.
TL;DR: It is demonstrated that incorporation of cholesterol into platelet membranes is associated with a diminished inhibitory effect of prostaglandin E, on platelet aggregation and therefore adenosine 3’:5’-monophosphate production in these platelets.
Journal ArticleDOI
Drug-Antibody-Platelet Interaction in Quinine- and Quinidine-induced Thrombocytopenia
TL;DR: It is demonstrated that in quinine- and quinidine-induced thrombocytopenia, drug and antibody combine first in the soluble phase to form a complex, which then binds with high affinity to a receptor on the platelet surface (innocent bystander reaction), and that these antibodies are heterogeneous in respect to the amount of drug required to promote their binding to platelets, the number of platelet receptors they recognize, and their binding affinities.