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

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