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Hamostaseologie 2014; 34(01): 78-84
DOI: 10.5482/HAMO-13-11-0055
Review
Schattauer GmbH

Direct oral anticoagulants and antiplatelet agents

Clinical relevance and options for laboratory testingDirekte orale Antikoagulanzien und ThrombozytenfunktionshemmerKlinische Relevanz und Möglichkeiten der Labordiagnostik
D. Sibbing
1   Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München
,
M. Spannagl
2   Haemostaseologische Ambulanz Campus Innenstadt,, Klinikum der Universität München, Ludwig-Maximilians-Universität München
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received: 04. November 2013

accepted in revised form: 20. November 2013

Publikationsdatum:
27. Dezember 2017 (online)

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Summary

Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition.

In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for ant-iplatelet treatment.

Zusammenfassung

Bei Patienten mit kardiovaskulären Krankheiten werden orale Antikoagulanzien und Thrombozytenaggregationshemmer häufig verwendet, um das Risiko für thrombotische Ereignisse zu reduzieren. Die regelmäßige Einnahme und suffiziente antithrombozytäre Wirkung ist ganz entscheidend für den einzelnen Patienten. Aus diesem Grund wurden pharmakinetische und pharmakodynamische Testverfahren entwickelt, um die Wirkung dieser Medikamente zu monitorieren. In der klinischen Routine finden diese Verfahren immer häufiger Anwendung. Ihre Verbreitung wird auch durch die Verfügbarkeit so genannter neuer direkter oraler Antikoagulanzien wie Dabigatran, Rivaroxaban und Apixaban als Alternative zu Vitamin-K-Antagonisten und neuer Plättchenaggregationshemmer wie Prasugrel und Ticagrelor als Alternative zu Clopidogrel unterstützt.

In dieser Übersichtsarbeit werden die wichtigsten und häufigsten Verfahren und ihre klinischen Implikationen in Bezug auf das Antikoagulanzien-und Plättchenaggregationshemmer-Monitoring vorgestellt.

Keywords

Oral anticoagulation - platelet aggregation - drug monitoring

Schlüsselwörter

Orale Antikoagulanzien - Plättchenaggregation - Drug-Monitoring
 

  • References

  • 1 Sibbing D, Orban M, Massberg S. Potent P2Y12 receptor inhibitors in patients with acute coronary syndrome. Agents, indications, issues to consider in clinical practice. Hämostaseologie 2013; 33: 9-15.
    Thieme ConnectPubMedSuche in Google Scholar
  • 2 Steiner T, Bohm M, Dichgans M. et al. Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. Clin Res Cardiol 2013; 102: 399-412.
    CrossrefPubMedSuche in Google Scholar
  • 3 Skov J, Bladbjerg EM, Rasmussen MA. et al. Genetic, clinical and behavioural determinants of vitamin K-antagonist dose – Explored through multivariable modelling and visualization. Basic Clin Pharmacol Toxicol. 2011 doi: 10.1111/j.1742–7843.2011.00789.x.
    PubMedSuche in Google Scholar
  • 4 Ageno W, Gallus AS, Wittkowsky A. et al. Oral anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis. Chest 2012; 141 (Suppl. 02) e44S-E88S.
    CrossrefPubMedSuche in Google Scholar
  • 5 Horsti J, Uppa H, Vilpo JA. Poor agreement among prothrombin time international normalized ratio methods: comparison of seven commercial reagents. Clin Chem 2005; 51: 553-560.
    CrossrefPubMedSuche in Google Scholar
  • 6 Chia S, Van Cott EM, Raffel OC. et al. Comparison of activated clotting times obtained using Hemochron and Medtronic analysers in patients receiving anti-thrombin therapy during cardiac catheterisation. Thromb Haemost 2009; 101: 535-540.
    Thieme ConnectPubMedSuche in Google Scholar
  • 7 Chew DP, Bhatt DL, Lincoff AM. et al. Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials. Circulation 2001; 103: 961-966.
    CrossrefPubMedSuche in Google Scholar
  • 8 Castellone DD, Van Cott EM. Laboratory monitoring of new anticoagulants. Am J Hematol 2010; 85: 185-187.
    PubMedSuche in Google Scholar
  • 9 Becker RC, Yang H, Barrett Y. et al. Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban--an oral, direct and selective factor Xa inhibitor. J Thromb Thrombolysis 2011; 32: 183-187.
    CrossrefPubMedSuche in Google Scholar
  • 10 Van Ryn J, Stangier J, Haertter S. et al. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116-1127.
    Thieme ConnectPubMedSuche in Google Scholar
  • 11 Cannegieter SC, van der Meer FJ, Briet E. et al. Warfarin and aspirin after heart-valve replacement. N Engl J Med 1994; 330: 507-509.
    CrossrefPubMedSuche in Google Scholar
  • 12 Erkens PM, ten Cate H, Buller HR. et al. Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and metaanalysis. PLoS One 2012; 07: e42269.
    CrossrefPubMedSuche in Google Scholar
  • 13 Dentali F, Riva N, Crowther M. et al. Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature. Circulation 2012; 126: 2381-2391.
    CrossrefPubMedSuche in Google Scholar
  • 14 Reilly PA, Lehr T, Haertter S. et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients in the RE-LY trial. J Am Coll Cardiol. 2013 doi: 10.1016/j.jacc.2013.07.104.
    PubMedSuche in Google Scholar
  • 15 Sibbing D, Taubert D, Schomig A. et al. Pharmacokinetics of clopidogrel in patients with stent thrombosis. J Thromb Haemost 2008; 06: 1230-1232.
    CrossrefPubMedSuche in Google Scholar
  • 16 Freynhofer MK, Bruno V, Willheim M. et al. Vasodilator-stimulated phosphoprotein-phosphorylation assay in patients on clopidogrel: does standardisation matter?. Thromb Haemost 2012; 107: 538-544.
    Thieme ConnectPubMedSuche in Google Scholar
  • 17 Jakubowski JA, Bourguet N, Boulay-Moine D. et al. Comparison of a new ELISA assay with the flow cytometric assay for platelet vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation in whole blood to assess P2Y(12) inhibition. Thromb Haemost 2012; 107: 388-395.
    Thieme ConnectPubMedSuche in Google Scholar
  • 18 Tantry US, Bonello L, Aradi D. et al. Consensus and update on the definition of on-treatment platelet reactivity to ADP associated with ischemia and bleeding. J Am Coll Cardiol. 2013 doi: 10.1016/j.jacc.2013.07.101.
    PubMedSuche in Google Scholar
  • 19 Aradi D, Storey RF, Komocsi A. et al. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J. 2013 doi: 10.1093/eurheartj/eht375.
    PubMedSuche in Google Scholar
  • 20 Stone GW, Witzenbichler B, Weisz G. et al. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPTDES). Lancet 2013; 382: 614-623.
    CrossrefPubMedSuche in Google Scholar
  • 21 Sibbing D, Gross L, Orban M. et al. Bleeding and thrombosis risk matters: how long can we stick to the one-size-fits-all strategy of platelet inhibition?. JACC Cardiovasc Interv 2013; 06: 864-866.
    CrossrefPubMedSuche in Google Scholar
  • 22 Mangiacapra F, Patti G, Barbato E. et al. A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE study. JACC Cardiovasc Interv 2012; 05: 281-289.
    CrossrefPubMedSuche in Google Scholar
  • 23 Campo G, Parrinello G, Ferraresi P. et al. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol 2011; 57: 2474-2483.
    CrossrefPubMedSuche in Google Scholar
  • 24 Sibbing D, Steinhubl SR, Schulz S. et al. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 2010; 56: 317-318.
    CrossrefPubMedSuche in Google Scholar
  • 25 Cuisset T, Grosdidier C, Loundou A. et al. Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study. JACC Cardiovasc Interv. 2013 in press. doi: 10.1016/j.jcin.2013.04.009.
    PubMedSuche in Google Scholar
  • 26 Bonello L, Mancini J, Pansieri M. et al. Relationship between post-treatment platelet reactivity and ischemic and bleeding events at 1-year follow-up in patients receiving prasugrel. J Thromb Haemost 2012; 10: 1999-2005.
    CrossrefPubMedSuche in Google Scholar
  • 27 Gurbel PA, Bliden KP, Navickas IA. et al. Adenosine diphosphate-induced platelet-fibrin clot strength: a new thrombelastographic indicator of long-term poststenting ischemic events. Am Heart J 2010; 160: 346-354.
    CrossrefPubMedSuche in Google Scholar
  • 28 Price MJ, Berger PB, Teirstein PS. et al. Standardvs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011; 305: 1097-1105.
    CrossrefPubMedSuche in Google Scholar
  • 29 Collet JP, Cuisset T, Range G. et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367: 2100-2109.
    CrossrefPubMedSuche in Google Scholar
  • 30 Trenk D, Stone GW, Gawaz M. et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: Results of the TRIGGER-PCI study. J Am Coll Cardiol 2012; 59: 2159-2164.
    CrossrefPubMedSuche in Google Scholar
  • 31 Siller-Matula JM, Francesconi M, Dechant C. et al. Personalized antiplatelet treatment after percutaneous coronary intervention: the MADONNA study. Int J Cardiol 2013; 167: 2018-2023.
    CrossrefPubMedSuche in Google Scholar
  • 32 Bonello L, Camoin-Jau L, Arques S. et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance. J Am Coll Cardiol 2008; 51: 1404-1411.
    CrossrefPubMedSuche in Google Scholar