Skip to main content
Top
Published in: Clinical Research in Cardiology 6/2012

01-06-2012 | Original Paper

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

Authors: Thomas Gremmel, Karin Frühwirth, Christoph W. Kopp, Alexandra Kaider, Sabine Steiner, Tamam Bakchoul, Ulrich J. H. Sachs, Renate Koppensteiner, Simon Panzer

Published in: Clinical Research in Cardiology | Issue 6/2012

Login to get access

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.
Literature
1.
go back to reference Gao C, Boylan B, Fang J, Wilcox DA, Newman DK, Newman PJ (2011) Heparin promotes platelet responsiveness by potentiating αIIβ3-mediated outside-in signaling. Blood 117:4946–4952PubMedCrossRef Gao C, Boylan B, Fang J, Wilcox DA, Newman DK, Newman PJ (2011) Heparin promotes platelet responsiveness by potentiating αIIβ3-mediated outside-in signaling. Blood 117:4946–4952PubMedCrossRef
2.
go back to reference Amiral J, Bridey F, Dreyfus M, Vissoc AM, Fressinaud E, Wolf M, Meyer D (1992) Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocyopenia. Thromb Haemost 68:95–96PubMed Amiral J, Bridey F, Dreyfus M, Vissoc AM, Fressinaud E, Wolf M, Meyer D (1992) Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocyopenia. Thromb Haemost 68:95–96PubMed
3.
go back to reference Gruel Y, Boizard-Boval B, Wautier JL (1993) Further evidence that alpha-granule components such as platelet factor 4 are involved in platelet-IgG-heparin interactions during heparin-associated thrombocytopenia. Thromb Haemost 70:374–375PubMed Gruel Y, Boizard-Boval B, Wautier JL (1993) Further evidence that alpha-granule components such as platelet factor 4 are involved in platelet-IgG-heparin interactions during heparin-associated thrombocytopenia. Thromb Haemost 70:374–375PubMed
4.
go back to reference Shantsila E, Lip GY, Chong BH (2009) Heparin-induced thrombocytopenia. A contemporary clinical approach to diagnosis and management. Chest 135:1651–1664PubMedCrossRef Shantsila E, Lip GY, Chong BH (2009) Heparin-induced thrombocytopenia. A contemporary clinical approach to diagnosis and management. Chest 135:1651–1664PubMedCrossRef
5.
go back to reference Kelton JG (2005) The pathophysiology of heparin-induced thrombocytopenia: biological basis for treatment. Chest 127:9S–20SPubMedCrossRef Kelton JG (2005) The pathophysiology of heparin-induced thrombocytopenia: biological basis for treatment. Chest 127:9S–20SPubMedCrossRef
6.
go back to reference Cattaneo M (2006) P2Y12 receptor antagonists: a rapidly expanding group of antiplatelet agents. Eur Heart J 27:1010–1012PubMedCrossRef Cattaneo M (2006) P2Y12 receptor antagonists: a rapidly expanding group of antiplatelet agents. Eur Heart J 27:1010–1012PubMedCrossRef
7.
go back to reference Neubauer H, Krüger JC, Lask S, Endres HG, Pepinghege F, Engelhardt A, Bulut D, Mügge A (2009) Comparing the antiplatelet effects of clopidogrel hydrogensulfate and clopidogrel besylate: a crossover study. Clin Res Cardiol 98:533–540PubMedCrossRef Neubauer H, Krüger JC, Lask S, Endres HG, Pepinghege F, Engelhardt A, Bulut D, Mügge A (2009) Comparing the antiplatelet effects of clopidogrel hydrogensulfate and clopidogrel besylate: a crossover study. Clin Res Cardiol 98:533–540PubMedCrossRef
8.
go back to reference Möllmann H, Nef H, Böhm M, Laufs U (2009) Highlights of the hotline sessions presented at the scientific sessions 2008 of the American Heart Association. Clin Res Cardiol 98:1–7PubMedCrossRef Möllmann H, Nef H, Böhm M, Laufs U (2009) Highlights of the hotline sessions presented at the scientific sessions 2008 of the American Heart Association. Clin Res Cardiol 98:1–7PubMedCrossRef
9.
go back to reference Ostad MA, Nick E, Paixao-Gatinho V, Schnorbus B, Schiewe R, Tschentscher P, Munzel T, Warnholtz A (2011) Lack of evidence for pleiotropic effects of clopidogrel on endothelial function and inflammation in patients with stable coronary artery disease: results of the double-blind, randomized CASSANDRA study. Clin Res Cardiol 100:29–36PubMedCrossRef Ostad MA, Nick E, Paixao-Gatinho V, Schnorbus B, Schiewe R, Tschentscher P, Munzel T, Warnholtz A (2011) Lack of evidence for pleiotropic effects of clopidogrel on endothelial function and inflammation in patients with stable coronary artery disease: results of the double-blind, randomized CASSANDRA study. Clin Res Cardiol 100:29–36PubMedCrossRef
10.
go back to reference Diehl P, Halscheid C, Olivier C, Helbing T, Bode C, Moser M (2011) Discontinuation of long term clopidogrel therapy induces platelet rebound hyperaggregability between 2 and 6 weeks post cessation. Clin Res Cardiol 100:765–771PubMedCrossRef Diehl P, Halscheid C, Olivier C, Helbing T, Bode C, Moser M (2011) Discontinuation of long term clopidogrel therapy induces platelet rebound hyperaggregability between 2 and 6 weeks post cessation. Clin Res Cardiol 100:765–771PubMedCrossRef
11.
go back to reference Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ (2005) Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 45:246–251PubMedCrossRef Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ (2005) Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 45:246–251PubMedCrossRef
12.
go back to reference Gurbel PA, Bliden KP, Etherington A, Tantry US (2007) Assessment of clopidogrel responsiveness: measurements of maximum platelet aggregation, final platelet aggregation and their correlation with vasodilator-stimulated phosphoprotein in resistant patients. Thromb Res 121:107–115PubMedCrossRef Gurbel PA, Bliden KP, Etherington A, Tantry US (2007) Assessment of clopidogrel responsiveness: measurements of maximum platelet aggregation, final platelet aggregation and their correlation with vasodilator-stimulated phosphoprotein in resistant patients. Thromb Res 121:107–115PubMedCrossRef
13.
go back to reference Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schomig A, Kastrati A, von Beckerath N (2009) Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 53:849–856PubMedCrossRef Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schomig A, Kastrati A, von Beckerath N (2009) Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 53:849–856PubMedCrossRef
14.
go back to reference Sibbing D, Morath T, Braun S, Stegherr J, Mehilli J, Vogt W, Schomig A, Kastrati A, von Beckerath N (2010) Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting. Thromb Haemost 103:151–159PubMedCrossRef Sibbing D, Morath T, Braun S, Stegherr J, Mehilli J, Vogt W, Schomig A, Kastrati A, von Beckerath N (2010) Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting. Thromb Haemost 103:151–159PubMedCrossRef
15.
go back to reference Siller-Matula JM, Christ G, Lang IM, Delle-Karth G, Huber K, Jilma B (2010) Multiple electrode aggregometry predicts stent thrombosis better than the vasodilator-stimulated phosphoprotein phosphorylation assay. J Thromb Haemost 8:351–359PubMedCrossRef Siller-Matula JM, Christ G, Lang IM, Delle-Karth G, Huber K, Jilma B (2010) Multiple electrode aggregometry predicts stent thrombosis better than the vasodilator-stimulated phosphoprotein phosphorylation assay. J Thromb Haemost 8:351–359PubMedCrossRef
16.
go back to reference Bonello L, Paganelli F, Arpin-Bornet M, Auquier P, Sampol J, Dignat-George F, Barragan P, Camoin-Jau L (2007) Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 5:1630–1636PubMedCrossRef Bonello L, Paganelli F, Arpin-Bornet M, Auquier P, Sampol J, Dignat-George F, Barragan P, Camoin-Jau L (2007) Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 5:1630–1636PubMedCrossRef
17.
go back to reference Marcucci R, Gori AM, Paniccia R, Giusti B, Valente S, Giglioli C, Buonamici P, Antoniucci D, Abbate R, Gensini GF (2009) Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation 119:237–242PubMedCrossRef Marcucci R, Gori AM, Paniccia R, Giusti B, Valente S, Giglioli C, Buonamici P, Antoniucci D, Abbate R, Gensini GF (2009) Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation 119:237–242PubMedCrossRef
18.
go back to reference Gurbel PA, Bliden KP, Guyer K, Cho PW, Zaman KA, Kreutz RP, Bassi AK, Tantry US (2005) Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study. J Am Coll Cardiol 46:1820–1826PubMedCrossRef Gurbel PA, Bliden KP, Guyer K, Cho PW, Zaman KA, Kreutz RP, Bassi AK, Tantry US (2005) Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study. J Am Coll Cardiol 46:1820–1826PubMedCrossRef
19.
go back to reference Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, Mansourati J, Mottier D, Abgrall JF, Boschat J (2008) Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 51:256–260PubMedCrossRef Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, Mansourati J, Mottier D, Abgrall JF, Boschat J (2008) Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 51:256–260PubMedCrossRef
20.
go back to reference Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW (2010) Calcium-channel blockers decrease clopidogrel-mediated platelet inhibition. Heart 96:186–189PubMedCrossRef Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW (2010) Calcium-channel blockers decrease clopidogrel-mediated platelet inhibition. Heart 96:186–189PubMedCrossRef
21.
go back to reference Sibbing D, von Beckerath N, Morath T, Stegherr J, Mehilli J, Sarafoff N, Braun S, Schulz S, Schomig A, Kastrati A (2010) Oral anticoagulation with coumarin derivatives and antiplatelet effects of clopidogrel. Eur Heart J 31:1205–1211PubMedCrossRef Sibbing D, von Beckerath N, Morath T, Stegherr J, Mehilli J, Sarafoff N, Braun S, Schulz S, Schomig A, Kastrati A (2010) Oral anticoagulation with coumarin derivatives and antiplatelet effects of clopidogrel. Eur Heart J 31:1205–1211PubMedCrossRef
22.
go back to reference Erlinge D, Varenhorst C, Braun OO, James S, Winters KJ, Jakubowski JA, Brandt JT, Sugidachi A, Siegbahn A, Wallentin L (2008) Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J Am Coll Cardiol 52:1968–1977PubMedCrossRef Erlinge D, Varenhorst C, Braun OO, James S, Winters KJ, Jakubowski JA, Brandt JT, Sugidachi A, Siegbahn A, Wallentin L (2008) Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J Am Coll Cardiol 52:1968–1977PubMedCrossRef
23.
go back to reference Angiolillo DJ, Bernardo E, Capodanno D, Vivas D, Sabate M, Ferreiro JL, Ueno M, Jimenez-Quevedo P, Alfonso F, Bass TA, Macaya C, Fernandez-Ortiz A (2010) Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy. J Am Coll Cardiol 55:1139–1146PubMedCrossRef Angiolillo DJ, Bernardo E, Capodanno D, Vivas D, Sabate M, Ferreiro JL, Ueno M, Jimenez-Quevedo P, Alfonso F, Bass TA, Macaya C, Fernandez-Ortiz A (2010) Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy. J Am Coll Cardiol 55:1139–1146PubMedCrossRef
24.
go back to reference Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW (2010) Adenosine diphosphate-inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel. J Thromb Haemost 8:37–42PubMedCrossRef Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW (2010) Adenosine diphosphate-inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel. J Thromb Haemost 8:37–42PubMedCrossRef
25.
go back to reference Bonello-Palot N, Armero S, Paganelli F, Mancini J, De Labriolle A, Bonello C, Levy N, Maillard L, Barragan P, Dignat-George F, Camoin-Jau L, Bonello L (2009) Relation of body mass index to high on-treatment platelet reactivity and of failed clopidogrel dose adjustment according to platelet reactivity monitoring in patients undergoing percutaneous coronary intervention. Am J Cardiol 104:1511–1515PubMedCrossRef Bonello-Palot N, Armero S, Paganelli F, Mancini J, De Labriolle A, Bonello C, Levy N, Maillard L, Barragan P, Dignat-George F, Camoin-Jau L, Bonello L (2009) Relation of body mass index to high on-treatment platelet reactivity and of failed clopidogrel dose adjustment according to platelet reactivity monitoring in patients undergoing percutaneous coronary intervention. Am J Cardiol 104:1511–1515PubMedCrossRef
26.
go back to reference Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360:354–362PubMedCrossRef Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360:354–362PubMedCrossRef
27.
go back to reference Geisler T, Mueller K, Aichele S, Bigalke B, Stellos K, Htun P, Ninci E, Fateh-Moghadam S, May AE, Gawaz M (2011) Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions. Clin Res Cardiol 99:743–752CrossRef Geisler T, Mueller K, Aichele S, Bigalke B, Stellos K, Htun P, Ninci E, Fateh-Moghadam S, May AE, Gawaz M (2011) Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions. Clin Res Cardiol 99:743–752CrossRef
28.
go back to reference Schwarz AK, Zahn R, Hochadel M, Kerber S, Hauptmann KE, Glunz HG, Mudra H, Darius H, Zeymer U (2011) Age-related differences in antithrombotic therapy, success rate and in-hospital mortality in patients undergoing percutaneous coronary intervention: results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK). Clin Res Cardiol 100:773–780PubMedCrossRef Schwarz AK, Zahn R, Hochadel M, Kerber S, Hauptmann KE, Glunz HG, Mudra H, Darius H, Zeymer U (2011) Age-related differences in antithrombotic therapy, success rate and in-hospital mortality in patients undergoing percutaneous coronary intervention: results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK). Clin Res Cardiol 100:773–780PubMedCrossRef
29.
go back to reference Zankl AR, Andrassy M, Volz C, Ivandic B, Krumsdorf U, Katus HA, Blessing E (2010) Radial artery thrombosis following transradial coronary angiography: incidence and rationale for treatment of symptomatic patients with low-molecular-weight heparins. Clin Res Cardiol 99:841–847PubMedCrossRef Zankl AR, Andrassy M, Volz C, Ivandic B, Krumsdorf U, Katus HA, Blessing E (2010) Radial artery thrombosis following transradial coronary angiography: incidence and rationale for treatment of symptomatic patients with low-molecular-weight heparins. Clin Res Cardiol 99:841–847PubMedCrossRef
30.
go back to reference Dziewierz A, Siudak Z, Rakowski T, Birkemeyer R, Mielecki W, Ranosz P, Dubiel JS, Dudek D (2011) Drug-eluting versus bare-metal stents in ST-segment elevation myocardial infarction: a mortality analysis from the EUROTRANSFER registry. Clin Res Cardiol 100:139–145PubMedCrossRef Dziewierz A, Siudak Z, Rakowski T, Birkemeyer R, Mielecki W, Ranosz P, Dubiel JS, Dudek D (2011) Drug-eluting versus bare-metal stents in ST-segment elevation myocardial infarction: a mortality analysis from the EUROTRANSFER registry. Clin Res Cardiol 100:139–145PubMedCrossRef
31.
go back to reference Selleng S, Malowsky B, Itterman T, Bagemuhl J, Wessel A, Wollert HG, Warkentin TE, Greinacher A (2010) Incidence and clinical relevance of anti-platelet factor 4/heparin antibodies before cardiac surgery. Am Heart J 160:362–369PubMedCrossRef Selleng S, Malowsky B, Itterman T, Bagemuhl J, Wessel A, Wollert HG, Warkentin TE, Greinacher A (2010) Incidence and clinical relevance of anti-platelet factor 4/heparin antibodies before cardiac surgery. Am Heart J 160:362–369PubMedCrossRef
32.
go back to reference Warkentin TE, Sheppard JA, Horsewood P, Simpson PJ, Moore JC, Kelton JG (2000) Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood 96:1703–1708PubMed Warkentin TE, Sheppard JA, Horsewood P, Simpson PJ, Moore JC, Kelton JG (2000) Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood 96:1703–1708PubMed
33.
go back to reference Pouplard C, May MA, Iochmann S, Amiral J, Vissac AM, Marchand M, Gruel Y (1999) Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin: clinical implications for heparin-induced thrombocytopenia. Circulation 99:2530–2536PubMed Pouplard C, May MA, Iochmann S, Amiral J, Vissac AM, Marchand M, Gruel Y (1999) Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin: clinical implications for heparin-induced thrombocytopenia. Circulation 99:2530–2536PubMed
34.
go back to reference Pouplard C, Regina S, May MA, Gruel Y (2007) Heparin-induced thrombocytopenia: a frequent complication after cardiac surgery. Arch Mal Coeur Vaiss 100:563–568PubMed Pouplard C, Regina S, May MA, Gruel Y (2007) Heparin-induced thrombocytopenia: a frequent complication after cardiac surgery. Arch Mal Coeur Vaiss 100:563–568PubMed
35.
go back to reference Mattioli AV, Bonetti L, Zennaro M, Ambrosio G, Mattioli G (2009) Heparin/PF4 antibodies formation after heparin treatment: temporal aspects and long-term follow-up. Am Heart J 157:589–595PubMedCrossRef Mattioli AV, Bonetti L, Zennaro M, Ambrosio G, Mattioli G (2009) Heparin/PF4 antibodies formation after heparin treatment: temporal aspects and long-term follow-up. Am Heart J 157:589–595PubMedCrossRef
36.
go back to reference Bennett-Guerrero E, Slaughter TF, White WD, Welsby IJ, Greenberg CS, El-Moalem H, Ortel TL (2005) Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery. J Thorac Cardiovasc Surg 130:1567–1572PubMedCrossRef Bennett-Guerrero E, Slaughter TF, White WD, Welsby IJ, Greenberg CS, El-Moalem H, Ortel TL (2005) Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery. J Thorac Cardiovasc Surg 130:1567–1572PubMedCrossRef
37.
go back to reference Pouplard C, Gueret P, Fouassier M, Ternisien C, Trossaert M, Regina S, Gruel Y (2007) Prospective evaluation of the ‘4Ts’ score and particle gel immunoassay specific to heparin/PF4 for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost 5:1373–1379PubMedCrossRef Pouplard C, Gueret P, Fouassier M, Ternisien C, Trossaert M, Regina S, Gruel Y (2007) Prospective evaluation of the ‘4Ts’ score and particle gel immunoassay specific to heparin/PF4 for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost 5:1373–1379PubMedCrossRef
38.
go back to reference Greinacher A, Michels I, Kiefel V, Mueller-Eckhardt C (1991) A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb Haemost 66:734–736PubMed Greinacher A, Michels I, Kiefel V, Mueller-Eckhardt C (1991) A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb Haemost 66:734–736PubMed
39.
go back to reference Morel-Kopp MC, Aboud M, Tan CW, Kulathilake C, Ward C (2010) Whole blood impedance aggregometry detects heparin-induced thrombocytopenia antibodies. Thromb Res 125:e234–e239PubMedCrossRef Morel-Kopp MC, Aboud M, Tan CW, Kulathilake C, Ward C (2010) Whole blood impedance aggregometry detects heparin-induced thrombocytopenia antibodies. Thromb Res 125:e234–e239PubMedCrossRef
40.
go back to reference Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, Bhatt DL, Cattaneo M, Collet JP, Cuisset T, Gachet C, Montalescot G, Jennings LK, Kereiakes D, Sibbing D, Trenk D, Van Werkum JW, Paganelli F, Price MJ, Waksman R, Gurbel PA (2010) Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 56:919–933PubMedCrossRef Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, Bhatt DL, Cattaneo M, Collet JP, Cuisset T, Gachet C, Montalescot G, Jennings LK, Kereiakes D, Sibbing D, Trenk D, Van Werkum JW, Paganelli F, Price MJ, Waksman R, Gurbel PA (2010) Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 56:919–933PubMedCrossRef
41.
go back to reference Greinacher A, Juhl D, Strobel U, Wessel A, Lubenow N, Selleng K, Eichler P, Warkentin TE (2007) Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes. J Thromb Haemost 5:1666–1673PubMedCrossRef Greinacher A, Juhl D, Strobel U, Wessel A, Lubenow N, Selleng K, Eichler P, Warkentin TE (2007) Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes. J Thromb Haemost 5:1666–1673PubMedCrossRef
42.
go back to reference Schallmoser K, Drexler C, Rohde E, Strunk D, Groselj-Strele A, Lanzer G, Kroll H, Panzer S (2009) The particle gel immunoassay as a rapid test to rule out heparin-induced thrombocytopenia? J Thorac Cardiovasc Surg 137:781–783PubMedCrossRef Schallmoser K, Drexler C, Rohde E, Strunk D, Groselj-Strele A, Lanzer G, Kroll H, Panzer S (2009) The particle gel immunoassay as a rapid test to rule out heparin-induced thrombocytopenia? J Thorac Cardiovasc Surg 137:781–783PubMedCrossRef
43.
go back to reference Selleng S, Malowsky B, Strobel U, Wessel A, Ittermann T, Wollert HG, Warkentin TE, Greinacher A (2010) Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positive. J Thromb Haemost 8:30–36PubMedCrossRef Selleng S, Malowsky B, Strobel U, Wessel A, Ittermann T, Wollert HG, Warkentin TE, Greinacher A (2010) Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positive. J Thromb Haemost 8:30–36PubMedCrossRef
44.
go back to reference Pouplard C, May MA, Regina S, Marchand M, Fusciardi J, Gruel Y (2005) Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin-dependent antibodies. Br J Haematol 128:837–841PubMedCrossRef Pouplard C, May MA, Regina S, Marchand M, Fusciardi J, Gruel Y (2005) Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin-dependent antibodies. Br J Haematol 128:837–841PubMedCrossRef
45.
go back to reference Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A (2006) Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 4:759–765PubMedCrossRef Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A (2006) Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 4:759–765PubMedCrossRef
46.
go back to reference Frelinger AL, Li Y, Linden MD, Tarnow I, Barnard MR, Fox ML, Michelson AD (2008) Aspirin ‘resistance’: role of pre-existent platelet reactivity and correlation between tests. J Thromb Haemost 6:2035–2044PubMedCrossRef Frelinger AL, Li Y, Linden MD, Tarnow I, Barnard MR, Fox ML, Michelson AD (2008) Aspirin ‘resistance’: role of pre-existent platelet reactivity and correlation between tests. J Thromb Haemost 6:2035–2044PubMedCrossRef
47.
go back to reference Frelinger AL 3rd, Furman MI, Linden MD, Li Y, Fox ML, Barnard MR, Michelson AD (2006) Residual arachidonic acid-induced platelet activation via an adenosine diphosphate-dependent but cyclooxygenase-1- and cyclooxygenase-2-independent pathway: a 700-patient study of aspirin resistance. Circulation 113:2888–2896PubMedCrossRef Frelinger AL 3rd, Furman MI, Linden MD, Li Y, Fox ML, Barnard MR, Michelson AD (2006) Residual arachidonic acid-induced platelet activation via an adenosine diphosphate-dependent but cyclooxygenase-1- and cyclooxygenase-2-independent pathway: a 700-patient study of aspirin resistance. Circulation 113:2888–2896PubMedCrossRef
48.
go back to reference Elalamy I, Galea V, Hatmi M, Gerotziafas GT (2009) Heparin-induced multiple electrode aggregometry: a potential tool for improvement of heparin-induced thrombocytopenia diagnosis. J Thromb Haemost 7:1932–1934PubMedCrossRef Elalamy I, Galea V, Hatmi M, Gerotziafas GT (2009) Heparin-induced multiple electrode aggregometry: a potential tool for improvement of heparin-induced thrombocytopenia diagnosis. J Thromb Haemost 7:1932–1934PubMedCrossRef
49.
go back to reference Eichler P, Budde U, Haas S, Kroll H, Loreth RM, Meyer O, Pachmann U, Potzsch B, Schabel A, Albrecht D, Greinacher A (1999) First workshop for detection of heparin-induced antibodies: validation of the heparin-induced platelet-activation test (HIPA) in comparison with a PF4/heparin ELISA. Thromb Haemost 81:625–629PubMed Eichler P, Budde U, Haas S, Kroll H, Loreth RM, Meyer O, Pachmann U, Potzsch B, Schabel A, Albrecht D, Greinacher A (1999) First workshop for detection of heparin-induced antibodies: validation of the heparin-induced platelet-activation test (HIPA) in comparison with a PF4/heparin ELISA. Thromb Haemost 81:625–629PubMed
50.
go back to reference Behr T, Kuch B, Behr W, von Scheidt W (2011) Optimizing of thienopyridine therapy by multiple electrode platelet aggregometry in clopidogrel low responders undergoing PCI. Clin Res Cardiol 100:907–914PubMedCrossRef Behr T, Kuch B, Behr W, von Scheidt W (2011) Optimizing of thienopyridine therapy by multiple electrode platelet aggregometry in clopidogrel low responders undergoing PCI. Clin Res Cardiol 100:907–914PubMedCrossRef
Metadata
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
Authors
Thomas Gremmel
Karin Frühwirth
Christoph W. Kopp
Alexandra Kaider
Sabine Steiner
Tamam Bakchoul
Ulrich J. H. Sachs
Renate Koppensteiner
Simon Panzer
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Clinical Research in Cardiology / Issue 6/2012
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-011-0411-3

Other articles of this Issue 6/2012

Clinical Research in Cardiology 6/2012 Go to the issue