PB0526 - Evaluation of intracerebral haematoma expansion of the new oral anticoagulants in rats.

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Roberto J C Fonseca

Professor
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
Rio de Janeiro, Rio de Janeiro, Brazil

Co-Author(s)

JF

Juliana Ferreira

Master's student
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Brasil
Rio de Janeiro, Rio de Janeiro, Brazil
GC

Gabriella Carvalho

Undergraduated student
Instituto de Ciências Biomédicas- ICB- UFRJ
Rio de Janeiro, Rio de Janeiro, Brazil
FP

Fernando Paiva

Professor
Instituto de Física de São Carlos/ Universidade de São Paulo
São Carlos, Sao Paulo, Brazil
PA

Paulo A. S. Mourão

Professor
UFRJ
Rio de Janeiro, Rio de Janeiro, Brazil

Background: Little is known about haematoma expansion that occurs after treatment with new oral anticoagulants (NOACs). Collagenase-induced intracerebral hemorrhage (ICH) model has been used to investigate this event in a translational approach.

Aims: In this work, we evaluated the effects of warfarin and NOACs (dabigatran, rivaroxaban and apixaban) on haematoma expansion in rats using an ICH model.

Methods: Oral anticoagulants were given by gavage at different doses and, at the peak of their anticoagulant and antithrombotic activities, ICH was induced by injecting collagenase VII-S (0.4U) into the left striatum. Haematomal lesion volume was determined 24h later using MRI, Evans Blue extravasation and H&E-stained brain sections. Neurological deficits were evaluated using Body Elevated Swing Test. Differences between groups were analyzed using analysis of variance followed by ANOVA test with Bioestat 5.0 software.

Results: At the highest dose (1.5 mg/kg), warfarin significantly increased hematoma volume ~3 fold, whereas no difference was observed with NOACs using T1-weighted analysis. Quantification of Evans Blue extravasation in the brains of animals treated with oral anticoagulants showed that warfarin at 1 and 1,5 mg/kg and dabigatran (9 mg/kg) increased intracerebral bleeding ~3 fold. We observed a clear correlation between the images obtained by magnetic resonance and by histological staining, but no differences were observed in neurological tests.

Conclusion(s): The evaluation of ICH by in vivo models should be performed using different methodologies to better evaluate the effect of different anticoagulants on the expansion of intracerebral bleeding.