Abstract WP73: No Influence of Dabigatran or its Specific Reversal Agent, Idarucizumab, on rTPA-induced Thrombolysis of Clots in Human Plasma: an in vitro Study
Oral anticoagulation reduces the elevated incidence of stroke in patients with atrial fibrillation. Though stroke risk is reduced, it is not entirely prevented. When patients present with ischemic stroke and are also being treated with newer oral anticoagulants, such as dabigatran, this can complicate therapy. Currently a specific reversal agent to dabigatran, idarucizumab, is in development and was shown to immediately reverse the anticoagulant effect of dabigatran in volunteers and patients.
However, it is unknown if administration of idarucizumab to reverse dabigatran results in any nonspecific effects on the action of rtPA. Thus this study was performed to determine the effect of dabigatran and its reversal with idarucizumab on rtPA-induced thrombolysis of a clot in human plasma in vitro.
Blood was obtained from volunteers after written informed consent. Clots were produced by adding thromboplastin and 200mM CaCl2 to platelet rich plasma containing 594Alexa-labelled fibrinogen at 37°C for 60 min. Clots were then removed, washed and added to plasma from the same subject containing 150 IU/mL rtPA ± dabigatran (150 ng/mL) for 1 hr. Idarucizumab (3 mg/mL) was added after 60 min and incubated for a further 60 min at 37°C, all under continuous stirring. Lysis was measured as fluorescence released into plasma from the clot. Data shown as mean ± SD, n=5, were compared with ANOVA, p<0.05 was significant.
Initial clot weight was similar (18±6 mg) across groups. Clots added to plasma containing only dabigatran or idarucizumab underwent no lysis. Incubation with rtPA resulted in 28±17, 34±18 and 61±18% lysis after 60, 65 and 120 min, respectively (p<0.001 vs control). Addition of dabigatran or idarucizumab alone did not significantly affect lysis in the presence of rtPA. Addition of dabigatran (at t=0) followed by idarucizumab (at t=60 min) to plasma resulted in similar rtPA-induced thrombolysis, 30±16, 34±14 and 55±17%, as compared to incubation with rtPA alone. Clot weight after 2 hrs was 6.3±2.2 mg with no difference across groups.
These data show there are no non-specific interactions of idarucizumab with rtPA-induced thrombolysis in this in vitro model. It reinforces the specificity of idarucizumab for only dabigatran and its lack of binding to other substrates.
Author Disclosures: J. van Ryn: Employment; Significant; Boehringer Ingelheim. J. Schurer: Employment; Significant; Boehringer Ingelheim. D. Fischer: Employment; Significant; Boehringer Ingelheim.
- © 2016 by American Heart Association, Inc.