Abstract 356: Resuscitation With Different Infusion Solutions does not Influence Binding of Dabigatran to its Specific Antidote in a Pig Model of Hemorrhagic Shock
Introduction: A specific antibody fragment (Fab) is currently in development to reverse the effects of dabigatran in cases of life-threatening bleeding or emergency surgery. In trauma, different volume expanders are used for resuscitation to compensate for blood loss and hemorrhagic shock, but it is unknown if these volume expanders can influence binding of dabigatran to the Fab. In this study we investigated whether frequently used infusion solutions affect binding of dabigatran to its antidote.
Methods: After ethical approval, pigs were treated for 3 days with dabigatran etexilate (DE, 30 mg/kg bid). Prior to hemorrhagic shock a 90 min infusion of dabigatran (30 min; 0.77mg/kg/h; 60 min: 0.26 mg/kg/min) was performed in anesthetized pigs. Then ~50% (100 mL/min) of total blood volume was removed. Animals were randomized to (n=5/group): balanced Ringer’s solution, 6% HES 130/0.4, 6% HES 200/0.5, 4% gelatin, transfusion of washed red blood cells (RBC) or control (no hemodilution). Resuscitation consisted of 1:1 to blood loss for crystalloids, 25 mL/kg for colloids, and 12 mL/kg for RBC. Antidote was then given (30 mg/kg iv) and serial blood samples were taken for up to 24 hrs to measure active dabigatran as diluted thrombin time (dTT) and total dabigatran (bound to antidote and free drug) by LC-MS/MS. Antidote concentrations were measured by ELISA and the half-life calculated in each group. Data expressed as mean ± SE and analyzed with ANOVA.
Results: Hemodilution caused a substantial reduction of hematological parameters (hemoglobin, platelets etc) with all agents, except after RBC transfusion and control. Mean plasma dabigatran levels were 640 ± 60 ng/mL after infusion and 625 ± 123 ng/mL after the ~50% hemodilution without significant differences between groups. Administration of 30 mg/kg iv Fab resulted in a comparable reduction of active dabigatran in all groups. In addition the amount of total dabigatran (bound to antidote and free drug) was not significantly different across groups. Half-life of Fab was 3.2 ± 0.1 hrs in control animals and was not significantly different in animals with hemodilution.
Conclusions: Clinically used infusion solutions for volume resuscitation do not interfere with binding of dabigatran to its specific antidote.
- © 2013 by American Heart Association, Inc.