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Hamostaseologie 2012; 32(04): 287-293
DOI: 10.5482/ha-2012030001
Konsens
Schattauer GmbH

Blutungsrisiko und Blutungsnotfälle unter Rivaroxaban

Periinterventionelles Hämostase managementRisk of bleeding and haemorrhagic complication with rivaroxabanPeriprocedural management of haemostasis
J. Koscielny
1   Institut für Transfusionsmedizin, Charité – Universitätsklinikum Berlin
,
J. Beyer-Westendorf
2   Bereich Thromboseforschung und Gerinnungs störungen am Universitäts-GefäßCentrum, Universitätsklinikum Carl Gustav Carus der TU Dresden
,
C. von Heymann
3   Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin Charité-Universitätsmedizin Berlin Campus Virchow- Klinikum
,
J. Braun
4   Innere Medizin I, Asklepios Klinik
,
R. Klamroth
5   Innere Medizin – Angiologie, Hämostaseologie und Pneumologie, Vivantes Klinikum Berlin
,
E. Lindhoff-Last
6   Gefäßzentrum, Schwerpunkt Angiologie/Hämostaseologie, Johann-Wolfgang-Goethe- Universitätsklinik Frankfurt am Main
,
A. Tiede
7   Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltrans - plantation, Medizinische Hochschule Hannover
,
M. Spannagl
8   Haemo staseologie – Campus Innenstadt, Klinikum der Universität München
› Author Affiliations
Further Information

Publication History

eingegangen: 20 July 2012

Publication Date:
28 December 2017 (online)

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Summary

Rivaroxaban, the first direct factor-Xa inhibitor anticoagulant, has been approved for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery, for stroke prophylaxis in patients with non-valvular atrial fibrillation and for the treatment of deep vein thrombosis. There is no requirement for coagulation monitoring with rivaroxaban in routine clinical practice. However, in certain clinical circumstances such as life-threatening bleeding or an emergency operation the measurement of the thromboplastin time with a sensitive reagent will deliver first information. A quantitative determination of rivaroxaban plasma concentration is possible using an anti-factor Xa assay.

In the case of a patient under long-term anticoagulation with rivaroxaban requiring an elective surgery, a discontinuation of rivaroxaban 20 to 30 hours before the operation is sufficient to normalize the associated bleeding risk, as long as the renal and liver function is normal. A longer interval should be taken into consideration, when the patient presents a renal and liver impairment or is of a higher age. In the event of an emergency operation effective rivaroxaban concentrations might be present. Nevertheless, we advise against using a prophylactic dose of factor concentrates. Recommendations: From a clinical perspective, in the event of a minor bleeding we recommend a temporary discontinuation of rivaroxaban, whereas for clinically relevant major or severe bleeding events a mechanical compression or a limited surgical i. e. interventional treatment is required. Supportive measures such as the administration of blood products or tranexamic acid might be beneficial. In addition to haemodynamic supportive measures life threatening bleeding events demand a comprehensive haemostasis management, as well as the application of PCC.

Zusammenfassung

Rivaroxaban ist zugelassen zur Thromboseprophylaxe nach elektivem Hüft- und Knie - gelenkersatz, zur Schlaganfallprophylaxe bei Vorhofflimmern und zur Therapie der tiefen Venenthrombose. Ein Monitoring der gerinnungshemmenden Wirkung ist in der klinischen Routine nicht nötig, bei lebensbedrohlichen Blutungen oder Notoperationen kann jedoch die mit einem empfindlichen Reagenz gemessene Thromboplastinzeit erste Informationen liefern. Quantitative Aussagen zu Plasmakonzentration sind über Anti- FXa-Assays möglich.

Bei Elektiveingriffen unter Langzeitantikoagulation mit Rivaroxaban ist zur Normalisierung des Blutungsrisikos bei normaler Nieren-und Leberfunktion ein Absetzen von Rivaroxaban 20 bis 30 Stunden vor der Operation ausreichend, ein längerer Abstand sollte bei eingeschränkter Nieren- und Leberfunktion sowie bei hohem Lebensalter erwogen werden. Empfehlungen: Bei aus klinischer Sicht leichten Blutungen ist ein passageres Absetzen von Rivaroxaban anzuraten, bei mittelschweren bis schweren Blutungen eine begrenzte chirurgische bzw. Interventionelle Versorgung. Weitere Maßnahmen wie die Gabe von Blutprodukten oder Tranexamsäure können indiziert sein. Vital bedrohliche Blutungen erfordern neben Maßnahmen zur hämo dynamischen Stabilisierung ein umfassendes Hämostasemanagement sowie die Anwendung von PPSB.

Keywords

Rivaroxaban - anticoagulants - bleedings - bleeding risk - management of haemostasis - perinterventional management

Schlüsselwörter

Rivaroxaban - Antikoagulanzien - Blutungen - Blutungsrisiko - Hämostasemanagement - periinterventionelles Management
 

  • Literatur

  • 1 Bayer AGPharma. Xarelto® (rivaroxaban) Summary of Product Characteristics. 2011 http://www.xarelto.com/html/downloads/Xarelto_Summary_of_Product_Characteristics_Dec2011.pdf (accessed on 9 January 2012).
    PubMedGoogle Scholar
  • 2 Perzborn E, Roehrig S, Straub A. et al. The discovery and development of rivaroxaban, an oral, direct Factor Xa inhibitor. Nat. Rev. Drug Discov 2011; 10: 61-75.
    CrossrefPubMedGoogle Scholar
  • 3 Lang D, Freudenberger C, Weinz C. In vitro metabolism of rivaroxaban – an oral, direct Factor Xa inhibitor – in liver microsomes and hepatocytes of rat, dog and man. Drug Metab Dispos 2009; 37: 1046-1055.
    CrossrefPubMedGoogle Scholar
  • 4 Weinz C, Schwarz T, Kubitza D. et al. Metabolism and excretion of rivaroxaban, an oral, direct Factor Xa inhibitor, in rats, dogs and humans. Drug Metab Dispos 2009; 37: 1056-1064.
    CrossrefPubMedGoogle Scholar
  • 5 Harbrecht U. Old and new anticoagulants. Hämostaseologie 2011; 31: 21-27.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Turpie AGG, Lassen MR, Eriksson BI. et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost 2011; 105: 444-453.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
    CrossrefPubMedGoogle Scholar
  • 8 Mega JL, Braunwald E, Mohanavelu S. et al. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet 2009; 374: 29-38.
    CrossrefPubMedGoogle Scholar
  • 9 Patel MR, Mahaffey KW, Garg J. et al. Prevention of stroke and systemic embolism using the oral direct Factor Xa inhibitor rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: the ROCKET AF trial. N Engl J Med 2011; 365: 883-891.
    CrossrefPubMedGoogle Scholar
  • 10 Mega JL, Braunwald E, Wiviott SD. et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2011; 366: 9-19.
    PubMedGoogle Scholar
  • 11 The EINSTEIN-PE Investigators. Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism. N Engl J Med 2012; 366: 1287-1297.
    CrossrefPubMedGoogle Scholar
  • 12 Lindhoff-Last E, Samama MM, Ortel TL. et al. Assays for measuring rivaroxaban:their suitability and limitations. Ther Drug Monit 2010; 32: 673-679.
    CrossrefPubMedGoogle Scholar
  • 13 Kubitza D, Becka M, Wensing G. et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59–7939 – an oral, direct Factor Xa inhibitor – after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 2005; 61: 873-880.
    CrossrefPubMedGoogle Scholar
  • 14 Mueck W, Eriksson BI, Bauer KA. et al. Population pharmacokinetics and pharmacodynamics of rivaroxaban – an oral, direct factor Xa inhibitor – in patients undergoing major orthopaedic surgery. Clin Pharmacokinet 2008; 47: 203-216.
    CrossrefPubMedGoogle Scholar
  • 15 Kubitza D, Becka M, Voith B. et al. Safety. Pharmacodynamics, and pharmacokinetics of single doses of BAY 59–7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther 2005; 78: 412-421.
    CrossrefPubMedGoogle Scholar
  • 16 Lindhoff-Last E, Samama MM, Ortel TL. et al. Assays for measuring rivaroxaban:their suitability and limitations. Ther Drug Monit 2010; 32: 673-679.
    CrossrefPubMedGoogle Scholar
  • 17 Mani H, Hesse C, Stratmann G, Lindhoff-Last E. Rivaroxaban differentially influences ex vivo global coagulation assays based on the administration time. Thromb Haemost 2011; 106: 1-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Haas S, Turpie A, Lassen M. et al. Prothrombin time and bleeding events in patients undergoing total hip or knee replacement surgery receiving 10 mg rivaroxaban. ASH 2009, Poster Session: Antithrombotic Therapy Poster II. 2099.
    PubMedGoogle Scholar
  • 19 Samama MM, Contant G, Spiro T. et al. Evaluationof the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls. Thromb Haemost 2012; 107: 379-387.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Mani H, Rohde G, Stratmann G. et al. Accurate determination of rivaroxaban levels requires different calibrator sets but not addition of antithrombin. Thromb Haemost 2012; 108: 191-198.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Mueck W, Lensing A, Agnelli G. et al. Rivaroxaban:Population pharmacokinetic analyses in patients treated for acute deepvein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. Clin Pharmacokinet 2011; 10: 675-686.
    PubMedGoogle Scholar
  • 22 Fachinformation Xarelto. Rote Liste. 2012
    PubMedGoogle Scholar
  • 23 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 McCormack PL. Tranexamic acid: A review of its use in the treatment of hyperfibrinolysis. Drugs 2012; 72: 585-617.
    CrossrefPubMedGoogle Scholar
  • 25 Fachinformation Cyklokapron® . Rote Liste (Dezember 2010).
    PubMed
  • 26 Spannagl M, Koscielny J, Kiesewetter H. Prokoagulatoren. In: Aktuelle Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten der Bundesärztekammer. 2009: 153-154.
    Google Scholar
  • 27 Guyatt GH, Akl EA, Crowther M, Gutterman DD. forthe American College of Chest Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis,9th ed. American College of Chest Physicians. Chest 2012; 141: 7S-47S.
    CrossrefPubMedGoogle Scholar
  • 28 Marlu R, Hodaj E, Paris A. et al. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban. Thromb Haemost 2012; 108: 217-224.
    Article in Thieme ConnectPubMedGoogle Scholar