• Alain Bel, Wasseem Borik, Simon Davidson, Jean-Marie Helies, Lev Stimmer, Stephen Fremes, Steven Zelenkofske, Christopher Rusconi, John Alexander, David Alexander, Philippe Menasché, and John Pepper.
• Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou Department of Cardiovascular Surgery, Paris, France.
• Eur J Cardiothorac Surg. 2016 Feb 1; 49 (2): 682-9.

ObjectivesHeparin and protamine are standard for anticoagulation and reversal for cardiopulmonary bypass (CPB). The REGADO biosciences protocol 1 (REG1) anticoagulant system, consisting of the Factor IXa (FIXa)-inhibitor pegnivacogin and its reversal agent (anivamersen), has been studied in patients undergoing coronary catheterization and in CPB in sheep and pigs. Prior to first human use in CPB, we wanted to test the safety and efficacy of REG1 in a primate model.MethodsFourteen baboons undergoing 2 h of CPB followed by 1 h of reperfusion were studied. Three received heparin/protamine and 11 received 1 of 2 doses of pegnivacogin followed by anivamersen. Thrombin-generating capacity was tested in additional in vitro experiments.ResultsTargeted drug levels and near-complete FIXa inhibition were achieved. Bypass was run uneventfully in all animals without any clotting in the circuit and bleeding was minimal in the two groups. However, in contrast to heparin-treated baboons, those receiving pegnivacogin/anivamersen displayed thrombi in the bypass cannulae upon cannulation and kidney cortical infarcts. Inter-species comparisons revealed that in the presence of high levels of FIXa inhibition, tissue factor-mediated thrombin generation in baboons was much higher than that in other species.ConclusionsThese data highlight the limitations of the baboon model for assessing factor-specific coagulation inhibitors during CPB. The justification for Phase 1 human studies using REG1 for CPB is unclear.© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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