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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

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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.

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Acknowledgments

The authors thank Beate Eichelberger, Daniela Koren and Daniela Seidinger for expert technical support.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

    Thomas Gremmel, Christoph W. Kopp, Sabine Steiner & Renate Koppensteiner

  2. Clinical Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Karin Frühwirth & Simon Panzer

  3. Core Unit for Medical Statistics and Informatics, Section of Clinical Biometrics, Medical University of Vienna, Vienna, Austria

    Alexandra Kaider

  4. Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

    Tamam Bakchoul & Ulrich J. H. Sachs

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  1. Thomas Gremmel
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Correspondence to Thomas Gremmel or Simon Panzer.

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Gremmel, T., Frühwirth, K., Kopp, C.W. et al. 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 101, 445–452 (2012). https://doi.org/10.1007/s00392-011-0411-3

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