Katrin Schmidt1, Kerstin Krüger1, Elisabeth Langer2,3, Martin Schmutzler4, Elke Johnen5, Klaus D Wernecke6, Christian von Heymann1,7, Mareike K Körber1. 1. Department of Anaesthesiology and Operative Intensive Care Medicine (CVK), Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. 2. Labor Berlin-Charité Vivantes, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany. 3. Institute for Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany. 4. Department of Anaesthesiology and Intensive Care Medicine, Sankt Joseph Krankenhaus, Berlin, Germany. 5. Department of Orthopaedics and Trauma Surgery, Sankt Joseph Krankenhaus, Berlin, Germany. 6. Sophisticated Statistical Analyses-SOSTANA, Vivantes Klinikum am Friedrichshain, Berlin, Germany. 7. Department of Anaesthesiology, Intensive Care and Pain Therapy, Vivantes Klinikum am Friedrichshain, Berlin, Germany.
Abstract
BACKGROUND: Apixaban is a direct oral anticoagulant (DOAC) with a specific inhibition of activated factor X (FXa). In case of bleeding or need of urgent surgery a direct antidote is not yet available. Off-label application of non-specific haemostatic agents, such as prothrombin complex concentrate (PCC) and recombinant FVIIa (rFVIIa), has been reported to reverse the effects of apixaban in in vitro and animal studies. The aim of this study is to measure the reversal potential of PCC and rFVIIa in patients with prophylactic apixaban concentrations. MATERIAL AND METHODS: Whole blood from patients under prophylactic therapy with apixaban was spiked with two doses of PCC or rFVIIa. Thromboelastometry (ROTEM®), prothrombin time (PT), and activated partial prothrombin time (aPTT) were performed. RESULTS: Prolongations in PT and aPTT were corrected by the different concentrates with variable efficacies (PCC<rFVIIa) for all time points after medication. Compared with baseline, the reversal effects ranged from partial correction (PCC) to overcorrection of the CT-ExTEM, PT and aPTT by rFVIIa. DISCUSSION: PCC partially reverses the effect of apixaban as measured by point-of-care coagulation testing and standard coagulation tests. Only rFVIIa reliably reverses apixaban anticoagulation.
BACKGROUND:Apixaban is a direct oral anticoagulant (DOAC) with a specific inhibition of activated factor X (FXa). In case of bleeding or need of urgent surgery a direct antidote is not yet available. Off-label application of non-specific haemostatic agents, such as prothrombin complex concentrate (PCC) and recombinant FVIIa (rFVIIa), has been reported to reverse the effects of apixaban in in vitro and animal studies. The aim of this study is to measure the reversal potential of PCC and rFVIIa in patients with prophylactic apixaban concentrations. MATERIAL AND METHODS: Whole blood from patients under prophylactic therapy with apixaban was spiked with two doses of PCC or rFVIIa. Thromboelastometry (ROTEM®), prothrombin time (PT), and activated partial prothrombin time (aPTT) were performed. RESULTS: Prolongations in PT and aPTT were corrected by the different concentrates with variable efficacies (PCC<rFVIIa) for all time points after medication. Compared with baseline, the reversal effects ranged from partial correction (PCC) to overcorrection of the CT-ExTEM, PT and aPTT by rFVIIa. DISCUSSION: PCC partially reverses the effect of apixaban as measured by point-of-care coagulation testing and standard coagulation tests. Only rFVIIa reliably reverses apixaban anticoagulation.
Authors: Michael R Lassen; Walter Ageno; Lars C Borris; Jay R Lieberman; Nadia Rosencher; Tiemo J Bandel; Frank Misselwitz; Alexander G G Turpie Journal: N Engl J Med Date: 2008-06-26 Impact factor: 91.245
Authors: Bengt I Eriksson; Lars C Borris; Richard J Friedman; Sylvia Haas; Menno V Huisman; Ajay K Kakkar; Tiemo J Bandel; Horst Beckmann; Eva Muehlhofer; Frank Misselwitz; William Geerts Journal: N Engl J Med Date: 2008-06-26 Impact factor: 91.245
Authors: Michael Rud Lassen; Gary E Raskob; Alexander Gallus; Graham Pineo; Dalei Chen; Ronald J Portman Journal: N Engl J Med Date: 2009-08-06 Impact factor: 91.245
Authors: Jonathan Douxfils; Christian Chatelain; Bernard Chatelain; Jean-Michel Dogné; François Mullier Journal: Thromb Haemost Date: 2013-06-13 Impact factor: 5.249
Authors: Deborah M Siegal; John T Curnutte; Stuart J Connolly; Genmin Lu; Pamela B Conley; Brian L Wiens; Vandana S Mathur; Janice Castillo; Michele D Bronson; Janet M Leeds; Florie A Mar; Alex Gold; Mark A Crowther Journal: N Engl J Med Date: 2015-11-11 Impact factor: 91.245
Authors: Anne-Marije Hulshof; Renske H Olie; Minka J A Vries; Paul W M Verhezen; Paola E J van der Meijden; Hugo Ten Cate; Yvonne M C Henskens Journal: Front Cardiovasc Med Date: 2021-12-22