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American Heart Association

Clinical Articles, News & Views

In vitro approaches to reversal of anticoagulant, apixaban, explored

Three approaches may reverse the activity of the new oral anticoagulant apixaban, when a person needs emergency surgery, for example, according to laboratory research presented in the American Heart Association’s Emerging Science Series webinar.1

Some of the therapeutic strategies that reverse warfarin may be effective with newer oral anticoagulants such as apixaban and rivaroxaban. The newer drugs require less frequent blood tests, have fewer interactions with foods and other medications and doses are less variable. In contrast, there is little information on how best to reverse the effects of newer anticoagulants, which can take 10–18 hours.

“Despite these advantages, there is one common side effect of all blood thinners that can be severe — excess bleeding,” said Dr Gines Escolar, study author and associate professor of haematology at the University of Barcelona in Spain.

Warfarin blocks vitamin K and if excess bleeding occurs, the drug’s action can be reversed by administering the vitamin. When quick reversal is urgent with warfarin, other faster steps are sometimes taken. Researchers tested these steps in the preliminary study.

Blood clotting agents can potentially counteract the effect of anticoagulants. In the lab, researchers added a high dose of apixaban (200 nanograms per milliliter) to blood from healthy donors. Then, they tested the blood-clotting response when three clotting agents were added: prothrombin complex concentrates (PCCs, 50 IU/kg), activated prothrombin complex concentrates (aPCCs, 75 IU/kg) and recombinant Factor VII (rFVIIa, 270 ug/kg). They found:

  • PCC and aPCC seemed more efficient than rFVIIa at restoring the generation of thrombin, an enzyme important in blood clotting
  • rFVIIa was the quickest to produce a compact blood clot, followed by aPCC and PCC
  • rFVIIa was most effective in studies with blood circulating through a damaged blood vessel, followed by PCC and aPCC.

“The good news is that the various lab tests applied indicate that these approaches may reverse the effects of apixaban,” Escolar said. “But, even with the favorable results in perfusion studies using a damaged vessel, we’re far from knowing what will work best in a bleeding patient. Resolving efficacy and safety issues will require a clinical trial.”

Apixaban is approved in Europe for preventing venous thromboembolism in adults after knee or hip replacement surgery. Application is under review for using apixaban to prevent stroke in people with atrial fibrillation.

References

1. The research is part of the American Heart Association’s Emerging Science Series, a free online webinar presentation. View the webinar at www.scientificsessions.org/emergingscience

Published on: June 25, 2012

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ENDORSED BY

  • ArrhythmiaAlliance
  • Stars
  • Anticoagulation Europe
  • Atrial Fibrillation Association
 

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