title: Two distinct subgroups of tirofiban-induced thrombocytopenia exist due to drug dependent antibodies that cause platelet activation and increased ischaemic events.
abstract: Tirofiban-associated thrombocytopenia is due to drug-dependent antibodies (DDAbs) directed against the GPIIb/IIIa complex which can bind after drug-induced conformational changes to the receptor complex. In such cases a higher incidence of myocardial infarction and mortality has been reported raising the possibility of platelet activation. We followed consecutive cases treated with tirofiban to determine the incidence of thrombocytopenia and confirmed that this was due to tirofiban-dependent antibodies. We then tested if these antibodies could cause platelet activation in vitro and correlated this with clinical outcome. In 871 treated patients, severe thrombocytopenia was observed in 11 cases, an incidence of 1.26%. Tirofiban dependent antibodies were confirmed in all cases using a flow cytometric assay. There were two distinct presentations of thrombocytopenia, one occurring acutely, and the second a delayed thrombocytopenia occurring after several days of tirofiban exposure and in keeping with a primary immune response. The effects of DDAbs on platelet activation was analysed by measuring P-selectin (CD62p) and annexin V, in the presence or absence of tirofiban, by flow cytometry. In addition, platelet activation was sought using the serotonin release assay. In six cases there was evidence of platelet activation and this was significantly associated with further coronary ischaemic events experienced at the time of acute thrombocytopenia. Tirofiban-induced thrombocytopenia due to DDAbs is a common occurrence and can lead to platelet activation and increased thrombotic events.
authors.affiliation: Department of Haematology, Prince of Wales Hospital, Level 4 Campus Centre, Randwick, Sydney, Australia. dunkley@sesahs.nsw.gov.au
authors.forename: Scott
authors.initials: S
authors.lastname: Dunkley
authors.forename: Sue
authors.initials: S
authors.lastname: Evans
authors.forename: Leonie
authors.initials: L
authors.lastname: Gaudry
authors.forename: Nigel
authors.initials: N
authors.lastname: Jepson
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000276:immunology*; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000139:chemically induced / Q000276:immunology*; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban