title: Frequency of heparin/platelet factor 4-dependent platelet antibodies in patients undergoing angioplasty and stenting for cardiovascular disease and their role for on-clopidogrel platelet reactivity.
abstract: BACKGROUND
  The frequency of heparin-induced platelet antibodies (H/PF4 antibodies) following heparin exposure during percutaneous intervention with stent implantation is unknown. These antibodies may activate platelets and therefore contribute to high on-clopidogrel residual platelet reactivity (HRPR).
  
  
  METHODS
  We screened 288 patients after angioplasty and stenting for H/PF4 antibodies by an IgG/A/M ELISA. The 44 (15.3%) positive samples were further evaluated for IgG only antibodies, by the particle gel immunoassay (PaGIA), the heparin induced platelet activation assay (HIPA) and MEA. Further, we determined on-treatment platelet reactivity by multiple electrode aggregometry (MEA) in these patients. In vivo platelet activation was assessed by P-selectin expression.
  
  
  RESULTS
  The prevalence of H/PF4 antibodies in the total patients' cohort was 15.3% (95% CI 11.3-20%) by the IgG/A/M ELISA, 9.4% (95% CI 6.3-13.4%) by the IgG ELISA, 11.5% (95% CI 8-15.7%) by PaGIA, 14.2% (95% CI 10.4-18.8%) by MEA, and 2.4% (95% CI 1-4.9%) by HIPA. On-treatment platelet reactivity was similar between patients without and with H/PF4 antibodies [39 AU (6-110 AU) vs. 41 AU (7-91 AU); P = 0.85]. HRPR was seen in 105 patients (37.5%), and occurred to a similar extent in patients without and with H/PF4 antibodies in all test systems (all P > 0.2). Further, there was no difference of the ELISA optical densities using the IgG/A/M or the IgG only ELISA between patients without or with HRPR (all P > 0.3). There was no significant difference of P-selectin expression between patients without or with H/PF4 antibodies (P = 0.97). Noteworthy, none of the patients who developed H/PF4 antibodies had heparin-induced thrombocytopenia or a thromboembolic event.
  
  
  CONCLUSIONS
  H/PF4 antibodies are not rare in patients undergoing angioplasty and stenting. However, these antibodies are not associated with the occurrence of HRPR.
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. thomas.gremmel@meduniwien.ac.at
authors.forename: Thomas
authors.initials: T
authors.lastname: Gremmel
authors.forename: Karin
authors.initials: K
authors.lastname: Frühwirth
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Kopp
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
authors.forename: Tamam
authors.initials: T
authors.lastname: Bakchoul
authors.forename: Ulrich J H
authors.initials: UJ
authors.lastname: Sachs
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D000906:Antibodies / Q000276:immunology; D000925:Anticoagulants / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000628:therapy*; D000077144:Clopidogrel; D004797:Enzyme-Linked Immunosorbent Assay; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000235:genetics; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010978:Platelet Factor 4 / Q000276:immunology*; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D007074:Immunoglobulin G; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D010978:Platelet Factor 4; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine