Solbeck, Sacha1; Meyer, Martin A S1; Johansson, Pär I1; Meyer, Anna Sina P3; Cotton, Bryan A4; Stensballe, Jakob2; Schött, Ulf5; Ostrowski, Sisse R1
1 Klinisk Immunologisk Afdeling. Blodbanken og Vævstypelaboratoriet, Diagnostisk Center, Rigshospitalet, The Capital Region of Denmark2 Anæstesi- og operationsklinikken HOC, HovedOrtoCentret Rigshospitalet, Rigshospitalet, The Capital Region of Denmark3 University of Copenhagen4 University of Texas5 Lund University Hospital
BACKGROUND: Dabigatran etexilate, a pro-drug of a direct thrombin inhibitor, was approved a few years ago for non-valvular atrial fibrillation and deep venous thrombosis. Rapid monitoring of the dabigatran level is essential in trauma and bleeding patients but the traditional plasma-based assays may not sufficiently display the effect. Furthermore, no antidote exists and reversal of the anticoagulant effect is impossible or difficult. The present study investigated the in vitro effect of dabigatran on whole blood thromboelastography (TEG) and its reversal by recombinant activated factor VII and prothrombin complex concentrate. METHODS: Blood was collected from 10 healthy donors and spiked in vitro with therapeutic doses of dabigatran to a plasma concentration of 200ng/ml, followed by therapeutic doses of recombinant activated factor VII (corresponding to 100μg/kg) and prothrombin complex concentrate (corresponding to 50IE/kg) and evaluated by TEG. RESULTS: Compared to baseline, dabigatran changed all TEG parameters in a hypocoagulable direction corresponding to increased R time and time to maximum rate of thrombus generation, reduced angle, A5, A10, maximum amplitude and maximum rate of thrombin formation. Recombinant activated factor VII had a procoagulant effect on the majority of the investigated TEG parameters when added to dabigatran spiked samples. Prothrombin complex concentrate appeared not to have a procoagulant effect on TEG even when the heparin content in the formulation was neutralized by heparinase. CONCLUSIONS: TEG displays the presence of dabigatran in whole blood in vitro and the anticoagulant effect of dabigatran is partly reversed by spiking with recombinant activated factor VII.
International Journal of Cardiology, 2014, Vol 176, Issue 3, p. 794-99