Skip to main content

Advertisement

SpringerLink
Log in

Variation in platelet expression of FcγRIIa after myocardial infarction

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

FcγRIIa amplifies platelet activation and greater platelet expression of FcγRIIa identifies patients at greater risk of subsequent cardiovascular events. Thus, platelet expression of FcγRIIa may be useful to guide therapy. Because platelet function tests are impacted by preparative procedures and substantial intra-individual variability, we examined the impact of these factors on platelet expression of FcγRIIa in blood from healthy subjects and in patients after myocardial infarction (MI). Platelet expression of FcγRIIa was quantified with the use of flow cytometry. Blood was taken from healthy subjects and 114 patients after a MI in whom platelet expression of FcγRIIa was quantified before discharge and at 6 ± 1 months. Neither anticoagulants nor the antiplatelet agent cangrelor changed platelet expression of FcγRIIa. Intra-individual variation in platelet FcγRIIa expression was 8.5% ± 5% over the course of 1 month in healthy subjects. Platelet FcγRIIa expression was within 20% of the baseline value after 6 months in 71% of patients after MI. In summary, because FcγRIIa is a protein on the surface of platelets, assay conditions and antiplatelet agents do not change expression. Intra-individual variability in platelet expression of FcγRIIa is modest. Accordingly, platelet expression of FcγRIIa is a marker of increased platelet reactivity that can be reliably and repeatedly measured.

Clinical Trial Registration: NCT02505217

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Boylan B, Gao C, Rathore V, Gill JC, Newman DK, Newman PJ (2008) Identification of FcgammaRIIa as the ITAM-bearing receptor mediating alphaIIbbeta3 outside-in integrin signaling in human platelets. Blood 112:2780–2786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lova P, Paganini S, Sinigaglia F, Balduini C, Torti M (2002) A Gi-dependent pathway is required for activation of the small GTPase Rap1B in human platelets. J Biol Chem 277:12009–12015

    Article  CAS  PubMed  Google Scholar 

  3. Calverley DC, Brass E, Hacker MR, Tsao-Wei DD, Espina BM, Pullarkat VA, Hodis HN, Groshen S (2002) Potential role of platelet FcgammaRIIA in collagen-mediated platelet activation associated with atherothrombosis. Atherosclerosis 164:261–267

    Article  CAS  PubMed  Google Scholar 

  4. Schneider DJ, McMahon SR, Chava S, Taatjes-Sommer HS, Meagher S, Ehle GL, Brummel-Ziedins KE (2018) FcγRIIa: a new cardiovascular risk marker. J Am Coll Cardiol 72:237–238

    Article  PubMed  Google Scholar 

  5. Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, Deneer VH, Harmsze AM, van der Heyden JA, Rensing BJ, Suttorp MJ, Hackeng CM, ten Berg JM (2010) Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA 303:754–762

    Article  CAS  PubMed  Google Scholar 

  6. Wisman PP, Roest M, Asselbergs FW, de Groot PG, Moll FL, van der Graaf Y, de Borst GJ (2014) Platelet-reactivity tests identify patients at risk of secondary cardiovascular events: a systematic review and meta-analysis. J Thromb Haemost 12:736–747

    Article  CAS  PubMed  Google Scholar 

  7. Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, Puri S, Robbins M, Garratt KN, Bertrand OF, Stillabower ME, Aragon JR, Kandzari DE, Stinis CT, Lee MS, Manoukian SV, Cannon CP, Schork NJ, Topol EJ, GRAVITAS Investigators (2011) Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 305:1097–1105

    Article  CAS  Google Scholar 

  8. Collet JP, Cuisset T, Rangé G, Cayla G, Elhadad S, Pouillot C, Henry P, Motreff P, Carrié D, Boueri Z, Belle L, Van Belle E, Rousseau H, Aubry P, Monségu J, Sabouret P, O’Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Barthélémy O, Beygui F, Silvain J, Vicaut E, Montalescot G, ARCTIC Investigators (2012) Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 367:2100–2109

    Article  CAS  PubMed  Google Scholar 

  9. Frelinger AL III, Bhatt DL, Lee RD, Mulford DJ, Wu J, Nudurupati S, Nigam A, Lampa M, Brooks JK, Barnard MR, Michelson AD (2013) Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite exclusion or control of polymorphisms (CYP2C19, ABCB1, PON1), noncompliance, diet, smoking, co-medications (including proton pump inhibitors), and pre-existent variability in platelet function. J Am Coll Cardiol 61:872–879

    Article  CAS  PubMed  Google Scholar 

  10. Hochholzer W, Ruff CT, Mesa RA, Mattimore JF, Cyr JF, Lei L, Frelinger AL III, Michelson AD, Berg DD, Angiolillo DJ, O’Donoghue ML, Sabatine MS, Mega JL (2014) Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial. J Am Coll Cardiol 64:361–368

    Article  PubMed  Google Scholar 

  11. Nührenberg TG, Stratz C, Leggewie S, Hochholzer W, Valina CM, Gick M, Kirtane AJ, Stone GW, Neumann FJ, Trenk D (2015) Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation. An ADAPT-DES substudy. Thromb Haemost 114:1020–1027

    Article  PubMed  Google Scholar 

  12. Schneider DJ, Tracy PB, Mann KG, Sobel BE (1997) Differential effects of anticoagulants on the activation of platelets ex vivo. Circulation 96:2877–2883

    Article  CAS  PubMed  Google Scholar 

  13. Madsen NJ, Holmes CE, Serrano FA, Sobel BE, Schneider DJ (2007) Influence of preparative procedures on assay of platelet function and apparent effects of antiplatelet agents. Am J Cardiol 100:722–727

    Article  CAS  PubMed  Google Scholar 

  14. Lippi G, Ippolito L, Zobbi V, Sandei F, Favaloro EJ (2013) Sample collection and platelet function testing: influence of vacuum or aspiration principle on PFA-100 test results. Blood Coagul Fibrinolysis 24:666–669

    Article  PubMed  Google Scholar 

  15. Brezinski DA, Tofler GH, Muller JE, Pohjola-Sintonen S, Willich SN, Schafer AI, Czeisler CA, Williams GH (1988) Morning increase in platelet aggregability. Association with assumption of the upright posture. Circulation 78:35–40

    Article  CAS  PubMed  Google Scholar 

  16. Kay S, Herishanu Y, Pick M, Rogowski O, Baron S, Naparstek E, Polliack A, Deutsch VR (2006) Quantitative flow cytometry of ZAP-70 levels in chronic lymphocytic leukemia using molecules of equivalent soluble fluorochrome. Cytometry 70B:218–226

    Article  CAS  Google Scholar 

  17. Quadrini KJ, Hegelund AC, Cortes KE, Xue C, Kennelly SM, Ji H, Högerkorp C-M, Mc Closky TW (2016) Validation of a flow cytometry-based assay to assess C5aR receptor occupancy on neutrophils and monocytes for use in drug development. Cytometry B 90B:177–190

    Article  CAS  Google Scholar 

  18. Rand MD, Lock JB, van’t Veer C, Gaffney DP, Mann KG (1996) Blood clotting in minimally altered whole blood. Blood 88:001–014

    Google Scholar 

  19. Schneider DJ, Sobel BE (2009) Streamlining the design of promising clinical trials: in vitro testing of antithrombotic regimens and multiple agonists of platelet activation. Coron Artery Dis 20:175–178

    Article  PubMed  Google Scholar 

  20. Karas SP, Rosse WF, Kurlander RJ (1982) Characterization of the IgG-Fc receptor on human platelets. Blood 60:1277–1282

    CAS  PubMed  Google Scholar 

  21. Cox D, Kerrigan SW, Watson SP (2011) Platelets and the innate immune system: mechanisms of bacterial-induced platelet activation. J Thromb Haemost 9:1097–1107

    Article  CAS  PubMed  Google Scholar 

  22. Arman M, Krauel K, Tilley DO, Weber C, Cox D, Greinacher A, Kerrigan SW, Watson SP (2014) Amplification of bacteria-induced platelet activation is triggered by FcγRIIA, integrin αIIbβ3, and platelet factor 4. Blood 123:3166–3174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kelton JG, Sheridan D, Santos A, Smith J, Steeves K, Smith C, Brown C, Murphy WG (1988) Heparin-induced thrombocytopenia: laboratory studies. Blood 72:925–930

    CAS  PubMed  Google Scholar 

  24. Reilly MP, Taylor SM, Hartman NK, Arepally GM, Sachais BS, Cines DB, Poncz M, McKenzie SE (2001) Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcgammaRIIA. Blood 98:2442–2447

    Article  CAS  PubMed  Google Scholar 

  25. Zhi H, Rauova L, Hayes V, Gao C, Boylan B, Newman DK, McKenzie SE, Cooley BC, Poncz M, Newman PJ (2013) Cooperative integrin/ITAM signaling in platelets enhances thrombus formation in vitro and in vivo. Blood 121:1858–1867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Braune S, Walter M, Schulze F, Lendlein A, Jung F (2014) Changes in platelet morphology and function during 24 hours of storage. Clin Hemorheol Microcirc 58:159–170

    CAS  PubMed  Google Scholar 

  27. Schneider DJ, Taatjes-Sommer HS (2009) Augmentation of megakaryocyte expression of FcgammaRIIa by interferon gamma. Arterioscler Thromb Vasc Biol 29:1138–1143

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported in part by a Grant from Janssen Pharmaceuticals, LLC.

Author information

Authors and Affiliations

  1. Departments of Medicine and Biochemistry, The University of Vermont, Burlington, VT, USA

    Sean R. McMahon, Sreedivya Chava, Heidi S. Taatjes-Sommer, Sean Meagher, Kathleen E. Brummel-Ziedins & David J. Schneider

  2. Cardiovascular Research Institute, The University of Vermont, 308 S. Park Drive, Colchester, Burlington, VT, 05446, USA

    Sean R. McMahon, Sreedivya Chava, Heidi S. Taatjes-Sommer, Sean Meagher, Kathleen E. Brummel-Ziedins & David J. Schneider

Authors
  1. Sean R. McMahon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sreedivya Chava
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heidi S. Taatjes-Sommer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sean Meagher
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathleen E. Brummel-Ziedins
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David J. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J. Schneider.

Ethics declarations

Conflict of interest

David J Schneider is named inventor on a pending patent application (Application No.: 14/403,337) that proposes the use of FcγRIIa for assaying platelet reactivity and treatment selection. The remaining authors have no disclosure.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McMahon, S.R., Chava, S., Taatjes-Sommer, H.S. et al. Variation in platelet expression of FcγRIIa after myocardial infarction. J Thromb Thrombolysis 48, 88–94 (2019). https://doi.org/10.1007/s11239-019-01852-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-019-01852-7

Keywords

Search

Navigation