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Comparative hemmorhagic studies on dabigatran, apixaban and rivaroxaban in a rat‐tail bleeding model
Author(s) -
Jeske Walter,
Escalante Vicki,
Walenga Jeanine M,
Hoppensteadt Debra,
Fareed Jawed,
Raake Wolfram
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb505
Subject(s) - rivaroxaban , dabigatran , apixaban , ex vivo , saline , medicine , anticoagulant , bleeding time , in vivo , pharmacology , anesthesia , major bleeding , surgery , warfarin , atrial fibrillation , platelet , platelet aggregation , microbiology and biotechnology , biology
The new oral anticoagulant drugs include dabigatran (D), apixaban (A) and (R) rivaroxaban which have been recently approved for various indications. These agents produce their anticoagulant effects by inhibiting either Factor IIa or FXa. These drugs exhibit distinct pharmacologic profiles. Bleeding represents a major complication with the use of these agents. This study was designed to compare the bleeding profile of the agents in a standardized rat tail bleeding model. Powdered forms of active D, A and R were commercially obtained and a working solution was prepared at 100 ug/ml. Groups of rats were administered saline or each of the agents at 100 ug/kg IV. Bleeding measurements were made 5 minutes after the administration. Blood samples were drawn at the end of bleeding time for ex vivo analysis. In comparison to saline treated animals (300 + 60 sec), the D group exhibited a markedly high bleeding time (2250 + 240 sec), A did not show any significant increase (320 + 80 sec), whereas R exhibited a moderate increase (1110 + 130 sec). Ex vivo analysis of blood did not detect any D or R; however, varying levels of A were measurable. These studies show that at an equivalent dose of 100 ug/kg D produced a markedly stronger bleeding response, R produced a lowered response and A did not show any bleeding effect. Ex vivo results indicate that the stronger bleeding effects with D and R may relate to non‐plasmatic mechanisms.