Thromb Haemost 2011; 105(01): 181-189
DOI: 10.1160/TH10-06-0393
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Apixaban decreases coagulation activity in patients with acute deep-vein thrombosis

Yu Chen Barrett
1   Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb Company, Princeton, New Jersey, USA
Jessie Wang
2   Global Biometric Sciences, Bristol-Myers Squibb Company, Princeton, New Jersey, USA
Robert Knabb
3   Global Clinical Research, Bristol-Myers Squibb Company, Princeton, New Jersey, USA
Puneet Mohan
3   Global Clinical Research, Bristol-Myers Squibb Company, Princeton, New Jersey, USA
› Author Affiliations
Financial support: This study was sponsored by Bristol-Myers Squibb and Pfizer Inc.
Further Information

Publication History

Received: 23 June 2010

Accepted after major revision: 01 October 2010

Publication Date:
22 November 2017 (online)


In patients with acute deep-vein thrombosis (DVT), apixaban, a direct oral factor Xa inhibitor, showed efficacy and safety similar to low-molecular-weight heparin followed by vitamin K antagonist (LMWH/VKA). We evaluated biomarkers of coagulation activity in relation to treatment dose, duration and clinical outcome. Patients (N = 520) with symptomatic DVT were randomised to receive apixaban (5 mg bid, 10 mg bid or 20 mg qd) or LMWH/VKA for 12 weeks. Plasma D-dimer, prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) levels were measured at baseline, and weeks 3 and 12 after treatment. Median plasma levels of D-dimer, F1+2 and TAT were elevated at baseline. At weeks 3 and 12, biomarker levels were normalised in most patients in all treatment groups, consistent with the low rate of venous thromboembolism (VTE) observed. Median reduction in D-dimer was similar in all treatment groups; percentage of patients with D-dimer above upper limit of normal decreased from 95% to 24–40% at week 12. F1+2 decline was greater with LMWH/VKA than apixaban. F1+2 in the apixaban groups changed to a similar extent (>84% of patients had F1+2 within reference range at week 12). Magnitude of TAT reduction was not quantifiable. In conclusion, levels of coagulation biomarkers decreased over 12 weeks of treatment with apixaban or LMWH/VKA in most patients with acute VTE. Baseline D-dimer and F1+2 were higher in patients with recurrent symptomatic VTE than in those without. Plasma levels of coagulation biomarkers did not appear to correlate with total bleeding events.

  • References

  • 1 Wells PS, Anderson DR, Rodger M. et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349: 1227-1235.
  • 2 Breddin HK, Kadziola Z, Scully M. et al. Risk factors and coagulation parameters in relationship to phlebographic response and clinical outcome in the treatment of acute deep vein thrombosis. Thromb Haemost 2003; 89: 272-277.
  • 3 Sadanaga T, Sadanaga M, Ogawa S. Evidence that D-dimer levels predict subsequent thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy. J Am Coll Cardiol 2010; 55: 2225-2231.
  • 4 Palareti G, Legnani C, Cosmi B. et al. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002; 87: 7-12.
  • 5 Palareti G, Cosmi B, Legnani C. et al. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355: 1780-1789.
  • 6 Cosmi B, Legnani C, Tosetto A. et al. Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study. Blood 2010; 115: 481-488.
  • 7 Kakkar VV, Hoppenstead DA, Fareed J. et al. Randomized trial of different regimens of heparins and in vivo thrombin generation in acute deep vein thrombosis. Blood 2002; 99: 1965-1970.
  • 8 Christersson C, Oldgren J, Bylock A. et al. Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischaemic events: observations from the ESTEEM Trial. Eur Heart J 2007; 28: 692-698.
  • 9 Wong PC, Crain EJ, Xin B. et al. Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost 2008; 06: 820-829.
  • 10 Lassen MR, Davidson BL, Gallus A. et al. The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost 2007; 05: 2368-2375.
  • 11 Lassen MR, Raskob GE, Gallus A. et al. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009; 361: 594-604.
  • 12 Lassen MR, Raskob GE, Gallus A. et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010; 375: 807-815.
  • 13 Buller H, Deitchman D, Prins M. et al. Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep vein thrombosis. The Botticelli DVT dose-ranging study. J Thromb Haemost 2008; 06: 1313-1318.
  • 14 Barrett YC, Wang J, Yu Z. et al. Apixaban treatment decreases coagulation activity in patients with acute deep-vein thrombosis. Presented at the 50th Annual Meeting of the American Society for Hematology, December 6–9, 2008; San Francisco, CA, USA.