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Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban—an oral, direct and selective factor Xa inhibitor

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Abstract

An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in clinical practice. We performed a pharmacokinetic and pharmacodynamic substudy in APPRAISE-1—a study of apixaban in patients with acute coronary syndrome(ACS). A total of 1691 patients had blood sampled for apixaban plasma concentrations using mass spectrometry/high performance liquid chromatography and anti-Xa activity using a chromogenic assay employing either low molecular weight heparin or apixaban as reference standards. Anti-Xa activity, determined by either anti-Xa-LMWH (r = 0.9671; P < 0.0001) or anti-Xa-apixaban (r = 0.9669; P < 0.0001) correlated strongly and in a linear fashion with apixaban plasma concentrations. The correlations for each method were equally strong at low (<100 ng/ml) (r = 0.86, P < 0.0001; r = 0.85, P < 0.0001), intermediate(100–200 ng/ml) (r = 0.73, P < 0.0001; r = 0.69, P < 0.0001) and high (>200 ng/ml) (r = 0.91, P < 0.0001; r = 0.91, P < 0.0001) plasma concentrations of apixaban, respectively. Our pharmacokinetic and pharmacodynamic substudy suggests that an apixaban-mediated anticoagulant effect can be detected even at very low plasma concentrations using a standard laboratory chromogenic anti-Xa assay with either LMWH or apixaban calibrators. While establishing parameters for safety and efficacy will require further investigation, an ability to discern the presence of a drug effect may provide clinically useful information.

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References

  1. Alexander JH, Becker RC et al (2009) Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial. Circulation 119(22):2877–2885

    Article  PubMed  Google Scholar 

  2. Barrett YC, Wang Z et al (2010) Clinical laboratory measurement of direct factor Xa inhibitors: Anti-Xa assay is preferable to prothrombin time assay. Thromb Haemost 104(6):1263–1271

    Article  PubMed  CAS  Google Scholar 

  3. Becker RC, Alexander JH et al (2010) Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome. Thromb Haemost 104(5):976–983

    Article  PubMed  CAS  Google Scholar 

  4. Jiang X, Crain EJ et al (2009) Apixaban, an oral direct factor Xa inhibitor, inhibits human clot-bound factor Xa activity in vitro. Thromb Haemost 101(4):780–782

    PubMed  CAS  Google Scholar 

  5. Samama MM, Martinoli JL et al (2010) Assessment of laboratory assays to measure rivaroxaban—an oral, direct factor Xa inhibitor. Thromb Haemost 103(4):815–825

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Richard C. Becker.

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Becker, R.C., 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 32, 183–187 (2011). https://doi.org/10.1007/s11239-011-0591-8

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  • DOI: https://doi.org/10.1007/s11239-011-0591-8

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