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

Clin Res Cardiol. 2012 Jun;101(6):445-52. doi: 10.1007/s00392-011-0411-3. Epub 2012 Jan 11.

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.

Conclusion: H/PF4 antibodies are not rare in patients undergoing angioplasty and stenting. However, these antibodies are not associated with the occurrence of HRPR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angioplasty, Balloon, Coronary / methods*
  • Antibodies / immunology
  • Anticoagulants / pharmacology
  • Cardiovascular Diseases / therapy*
  • Clopidogrel
  • Enzyme-Linked Immunosorbent Assay
  • Heparin / pharmacology*
  • Humans
  • Immunoassay / methods
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • P-Selectin / genetics
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Factor 4 / immunology*
  • Stents
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology

Substances

  • Antibodies
  • Anticoagulants
  • Immunoglobulin G
  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Platelet Factor 4
  • Heparin
  • Clopidogrel
  • Ticlopidine