Development of an Oral Anticoagulation Strategy for Permanent Artificial Lung Support

Area of Science:

• Cardiovascular Research
• Biomedical Engineering
• Pharmacology

Background:

• Extracorporeal membrane oxygenation (ECMO) is under development for permanent respiratory support as an alternative to lung transplantation.
• Direct oral anticoagulants offer potential advantages over heparin, including oral administration and predictable pharmacokinetics.

Purpose of the Study:

• To evaluate the artificial surface anticoagulation efficacy of rivaroxaban in an ECMO model.
• To compare rivaroxaban's efficacy with heparin in sheep models.

Main Methods:

• Three studies assessed rivaroxaban's pharmacology in sheep at varying doses (0.25, 0.5, 1 mg/kg).
• Artificial surface anticoagulation efficacy was compared between rivaroxaban and heparin in short-term and extended-duration mini-ECMO models.
• Simulated oral pharmacokinetics were used in the extended-duration model.

Main Results:

• Sheep exhibited a higher volume of distribution and shorter half-life for rivaroxaban compared to humans, with a similar linear relationship between prothrombin time and plasma concentration.
• The 0.5 mg/kg rivaroxaban dose demonstrated device survival times comparable to heparin in both short-term (51.3 vs. 57.5 min) and extended-duration (6.3 vs. 6.3 h) ECMO models.
• Calculated rivaroxaban exposure aligned with clinically approved oral doses.

Conclusions:

• Rivaroxaban demonstrates artificial surface anticoagulation efficacy comparable to heparin.
• The evaluated dosages of rivaroxaban are feasible for oral administration in humans.
• Future research will involve a 10-day full-scale ovine ECMO model to further assess rivaroxaban anticoagulation.