Changes in platelet function and reactivity induced by quinine in relation to quinine (drug) induced immune thrombocytopenia.
Quinine, a drug known to induce immune mediated thrombocytopenia, has been postulated to mediate binding of drug dependent antibodies to a range of platelet membrane glycoproteins. Quinine may not act solely as a hapten however, as we have shown that it inhibits platelet aggregation (ex vivo and in vitro) and release and modifies the ability of activated platelets to bind the adhesive proteins fibrinogen and fibronectin in a dose dependent fashion. Studies on the effect of quinine on the binding of monoclonal antibodies HuPlml (GpIIIa) FMC25 (GpIX) and AN51 (GpIb) to platelets shows a selective reduction in AN51 binding. In addition quinine induced platelet antibodies from thrombocytopenic patients, in the presence of quinine, have been shown to inhibit binding of these monoclonal antibodies to platelets to varying degrees. These observations suggest that quinine causes widespread but specific conformational changes in platelet membrane antigens which may expose neoantigens resulting in the production of quinine induced antibodies.
Connellan
J M
JM
Department of Haematology, Austin Hospital, Heidelberg, Victoria, Australia.
Deacon
S
S
Thurlow
P J
PJ
D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000378:metabolism; D066298:In Vitro Techniques; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011803:Quinine / Q000494:pharmacology*; D013921:Thrombocytopenia / Q000097:blood* / Q000139:chemically induced* / Q000276:immunology
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D007074:Immunoglobulin G; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen; D011803:Quinine