Dabigatrán intravenoso para la anticoagulación durante la circulación extracorpórea en un modelo ovino

BACKGROUND: Heparin is the standard anticoagulant used during cardiopulmonary bypass (CPB). However, there are problems with heparin, including immunogenicity and variability of effect, that make a search for an alternative desirable. Dabigatran anticoagulation has been reported to provide adequate conditions for CPB in a rabbit model. This study used a sheep model of CPB to assess the efficacy of dabigatran and its reversibility with idarucizumab. METHODS: Twelve sheep were subjected to 120 min of CPB after anticoagulation with either intravenous dabigatran or heparin (N = 6 per group). In both groups, activated clotting time, kaolin/tissue factor-activated thromboelastography reaction time, and blood gases were monitored during and after CPB. Plasma dabigatran concentrations were measured during and after CPB. After CPB, two sections of each arterial filter were examined for thrombus using electron microscopy. Idarucizumab or protamine was administered after CPB to reverse anticoagulation, and the sheep were monitored for a subsequent 24 h. Plasma concentrations of inflammatory and coagulation markers were assessed at baseline, after 120 min of CPB, and 6 h after reversal administration. RESULTS: After 120 min of CPB, there was no visible thrombus or fibrin observed on the arterial line filters in either the dabigatran or heparin groups. Plasma dabigatran concentrations during CPB were below the target concentration (5 µg/ml), ranging from 1.7 ± 0.4 to 3.4 ± 1.5 µg/ml. In both groups, reaction time and activated clotting time values increased during CPB and then returned to nearly baseline levels after administration of the reversal agents. Interleukin-6 concentrations were elevated in the heparin group compared to the dabigatran group. Five sheep survived 24 h after idarucizumab administration. Four of six sheep survived 24 h after the administration of protamine. CONCLUSIONS: This study demonstrates that dabigatran effectively provides anticoagulation in a sheep CPB model, and idarucizumab successfully reverses its effects.

Resumen tomado de PubMed (NCBI) para el registro citado, en el idioma original. La versión de referencia es la de la publicación original.

El resumen se deja sin traducir para conservar la redacción original de los autores.

Seis ovejas por grupo recibieron 120 min de CEC bajo dabigatrán intravenoso o heparina. En los filtros arteriales no hubo trombos visibles ni fibrina; el dabigatrán (1,7 ± 0,4 a 3,4 ± 1,5 µg/ml) quedó bajo el objetivo (5 µg/ml). Tras idarucizumab o protamina, el TCA y el tiempo de reacción recuperaron casi los valores basales; sobrevivieron 24 h cinco y cuatro animales, respectivamente. Para los autores, el dabigatrán anticoagula eficazmente en la CEC y el idarucizumab lo revierte.

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