Perioperatives Management unter den nicht Vitamin-K-abhängigen Antikoagulanzien

Ziel des Forschungsprojektes

Für die nicht Vitamin-K-abhängigen Antikoagulanzien (NOAK) stehen keine Antidote in der (sub-)akuten perioperativen Situation zur Verfügung. Zudem existieren keine einheitlichen Empfehlungen und / oder Leitlinien zu dieser Problematik, da u. a. keine entsprechenden prospektiven (randomisierten) klinischen Studien oder Registerdaten zu Patienten mit akuten Blutungen vorliegen. Auch für Blutungen unter den alten Antikoagulanzien fehlen im Wesentlichen derartige Untersuchungen.

• Literaturverzeichnis

• 1 Van Ryn J, Strangier 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
• 2 Cuker A, Siegal D, Crowther M, Garcia D. Laboratory Measurement of the Anticoagulant Activity of the Non–Vitamin K Oral Anticoagulants. J Am Coll Cardiol 2014; 64: 1128-1139
• 3 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
• 4 Lindhoff-Last E, Samama MM, Ortel TL et al. Assays for measuring rivaroxaban: their suitability and limitations. Ther Drug Monit 2010; 32: 673-679
• 5 Koscielny J, Beyer-Westendorf J, von Heymann C et al. „Risk of bleeding and haemorrhagic complication with rivaroxaban – periprocedural management of haemostasis“. Hamostaseologie 2012; 32: 287-293
• 6 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, Abstract 2099
• 7 FDA Drug Safety Communication from 05-13-2014: FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin. Update on the risk for serious bleeding events with the anticoagulant Pradaxa (dabigatran) that was issued on November 2, http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm Letzter Zugriff am 9.04.2015 2012
• 8 Graham DJ, Reichman ME, Wernecke M et al. Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated with Dabigatran or Warfarin for Non-Valvular Atrial Fibrillation. Circulation 2014; Oct 30. pii: CIRCULATIONAHA.114.012061
• 9 Beyer-Westendorf J, Förster K, Pannach S et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124: 955-962
• 10 Spannagl M, Bauersachs R, Debus ES et al. Dabigatran therapy – perioperative management and interpretation of coagulation tests. Hamostaseologie 2012; 32: 294-305
• 11 Giebl A, Gürtler K. Neue orale Antikoagulanzien in der perioperativen Medizin. Anaesthesist 2014; 63: 347-364
• 12 Eisele R, Melzer N, Bramlage P. Perioperatives Gerinnungsmanagement bei oraler Antikoagulation. Chirurg 2014; 85: 513-519
• 13 Pernod G, Albaladejo P, Godier A et al. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: Proposals of the Working Group on Perioperative Haemostasis (GIHP) – March 2013. Arch Cardiovasc Dis 2013; 106: 382-393
• 14 Spannagl M, Koscielny J, Kiesewetter H. Aktuelle Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten der Bundesärztekammer (. Kapitel 7: Prokoagulatoren: 4.. Auflage 2009: 153-154
• 15 Heidbuchel H, Verhamme P, Alings M et al. EHRA Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013; 27: 1-13
• 16 Koscielny J, Rutkauskaite E. Rivaroxaban and Hemostasis in Emergency Care. Emerg Med Int 2014; 9-18 Article ID 935474
• 17 Guyatt GH, Akl EA, Crowther M et al. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians. Chest 2012; 141: 7S-47S
• 18 Chang D, Dager W, Chin A. Removal of dabigatran by hemodialysis. Am J Kidney Dis 2013; 61: 487-489
• 19 Gruber A, Marzec U, Buetehorn U et al. Potential of Activated Prothrombin Complex Concentrate and Activated Factor VII to Reverse the Anticoagulant Effects of Rivaroxaban in Primates. Blood 2008; Poster Session: Antithrombotic Therapy Poster, Abstract 3825
• 20 Eerenberg ES, Kamphuisen PW, Sijpkens MK et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011; 124: 1573-1579
• 21 Kaatz S, Crowther M. Reversal of target-specific oral anticoagulants. J Thromb Thrombolysis 2013; 36: 195-202
• 22 Dager W, Roberts A. Reversing dabigatran in a life-threatening bleed occurring during cardiac ablation with factor eight inhibitor bypassing activity. Critical Care Medicine 2013; 41: 42-46
• 23 Warkentin TE, Margetts P, Connolly SJ et al. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood 2012; 119: 2172-2174
• 24 Lu G, DeGuzman F, Hollenbach S et al. A specific antidote for reversal on anticoagulation by direct and indirect inhibitors of coagulation Factor Xa“. Nat Med  2013; 19: 446-451
• 25 Crowther M et al. Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial Demonstrating Reversal Of Rivaroxaban-Induced Anticoagulation In Healthy Subjects By Andexanet Alfa (PRT064445), An Antidote For Fxa Inhibitors. Blood 2013; Poster Session: Antithrombotic Therapy Poster II, Abstract 3636
• 26 FDA. Adexanet-alfa. http://www.clinicaltrials.gov NCT01758432
• 27 FDA. Idarucizumab. http://www.clinicaltrials.gov NCT01688830
• 28 Glund S, Stangier J, Schmohl M et al. Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects, Blood. Session: 332. Antithrombotic Therapy: Anticoagulant Therapy, 2014, Session 342. Antithrombotic Therapy: Anticoagulant Therapy, 2014, Abstract 344, San Francisco: American Society of Hematology; 2014
• 29 Laulicht B, Bakhru S, Jiang X et al. Antidote for new oral anticoagulants: mechanism of action and binding specificity of PER977. J Thromb Haemost 2013; 11 (Suppl. 02) Abstract AS 47.1
• 30 Lu G, Kotha J, Cárdenas J et al. In vitro Characterization of Adexanet Alfa (PRT064445), a Specific fXa Inihibitor Antidote versus Aripazine (PER977), A Non-Specific Reversal Agent. Chicago: American Heart Association; 2014. Poster 3184
• 31 Heidbuchel H, Verhamme P, Alings M et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013; 15: 625-651