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Effects of thromboprophylactic doses of apixaban and rivaroxaban on coagulation and thrombin generation in association with total hip replacement

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Abstract

Factor Xa inhibitors (FXaI) apixaban and rivaroxaban are used for thromboprophylaxis after major elective orthopaedic surgery. Because few patient sample studies exist, we postoperatively assessed patients undergoing unilateral total hip arthroplasty, including 22 treated with apixaban (2.5 mg BID) and 20 treated with rivaroxaban (10 mg OD). We collected blood samples before and 3 h after drug intake at 4 time points, preoperatively, as well as on day 1, week 1 (day 2–8) and day 28 post-operation. APTT and PT were immediately analysed. Calibrated anti-FXa activity, Russel’s Viper Venom Time (RVVT) and thrombin generation (TG; Calibrated Automated Thrombogram®) captured the effects of FXaI on coagulation and TG. APTT and PT remained within the reference interval throughout, and did not correlate with FXaI levels (PT R2 = 0.44, APTT R2 = 0.07). Mean apixaban concentration at the peak varied by eightfold (19–153 ng/mL), but rivaroxaban only by 1.5-fold (111–183 ng/mL). Rivaroxaban, but not apixaban prolonged RVVT at peak levels. Both FXaIs had a prolonged lag time of TG (p < 0.001). Rivaroxaban decreased ETP peak at all time points and reached a minimum at day 28 (540 nM/min at rivaroxaban 184 ng/mL, p < 0.001), while rivaroxaban trough levels were low and ETP values normal. However, with apixaban, after an initial decrease, ETP did not differ between peak and trough levels until decreasing on day 28 at peak (990 nM/min at apixaban 112 ng/mL, p = 0.005). In conclusion, due to different dosing and pharmacology rivaroxaban and apixaban distinctly inhibited TG under postoperative conditions.

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Acknowledgements

The study was supported by the Helsingin ja Uudenmaan Sairaanhoitopiiri (Grant No. TYH 2015312). The authors sincerely acknowledge the contributions of Jaana Leiviskä, PhD, and Jari Leinonen, PhD, for implementing the rivaroxaban and apixaban calibrated anti-Xa assays, and laboratory technician Marja Lemponen is acknowledged for performing the coagulation analyses.

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Authors and Affiliations

  1. Coagulation Disorders Unit, Clinical Chemistry, HUSLAB Laboratory Services, Helsinki University Hospital, Helsinki, Finland

    Tuukka A. Helin & Lotta Joutsi-Korhonen

  2. Coagulation Disorders Unit, Hematology and Clinical Chemistry (HUSLAB Laboratory Services), Helsinki University Hospital, and University of Helsinki, POB 340, 00029, Helsinki, Finland

    Lauri Virtanen & Riitta Lassila

  3. Orton Orthopaedic Hospital, Helsinki, Finland

    Mikko Manninen

  4. Peijas Hospital, Helsinki University Hospital, Vantaa, Finland

    Jarkko Leskinen

  5. Oulu University Hospital, Oulu, Finland

    Juhana Leppilahti

  6. CSO of Aplagon Ltd, Helsinki, Finland

    Riitta Lassila

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  1. Tuukka A. Helin
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Correspondence to Riitta Lassila.

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All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration as well as its later amendments or comparable ethical standards.

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Helin, T.A., Virtanen, L., Manninen, M. et al. Effects of thromboprophylactic doses of apixaban and rivaroxaban on coagulation and thrombin generation in association with total hip replacement. J Thromb Thrombolysis 43, 562–569 (2017). https://doi.org/10.1007/s11239-017-1492-2

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