Desarrollo de una estrategia de anticoagulación oral para el soporte pulmonar artificial permanente

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) systems for permanent respiratory support are currently under development as an alternative to lung transplantation. Direct oral anticoagulants are a promising alternative to heparin due to their oral administration and predictable pharmacology. METHODS: The efficacy of rivaroxaban for artificial surface anticoagulation was evaluated using 3 studies that determined (1) the pharmacological behavior of 0.25, 0.5, and 1 mg/kg doses of rivaroxaban in sheep; (2) the artificial surface anticoagulation efficacy of these 3 doses compared with heparin in a short-term mini-ECMO model; and (3) the efficacy of the optimal dose from study 2 with simulated oral pharmacokinetics in an extended-duration mini-ECMO model. RESULTS: Study 1 found that sheep have a higher volume of distribution (2.2 ± 0.4 L/kg) and a shorter half-life (1.4 ± 0.1 h) for rivaroxaban than humans but a similar linear relationship between prothrombin time and rivaroxaban plasma concentration. In study 2, device survival time in the heparin group (57.5 ± 13.0 min) was most similar to the 0.5 mg/kg rivaroxaban group (51.3 ± 8.8 min; P  = 0.287). This dose was selected for study 3, and no difference was found in device survival time between heparin (6.3 ± 1.3 h) and the 0.5 mg/kg rivaroxaban infusion (6.3 ± 1.6 h; P  = 0.837). Furthermore, the calculated rivaroxaban exposure was similar to the clinically approved oral rivaroxaban doses (24-h area under the plasma concentration curve = 2074 µg h/L). CONCLUSIONS: These results demonstrate that rivaroxaban has artificial surface anticoagulation efficacy similar to that of heparin at dosages that are feasible for oral administration in humans. Future studies will evaluate rivaroxaban anticoagulation using a 10-d full-scale ovine ECMO model.

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.

Tres estudios evaluaron la farmacología de rivaroxabán en ovejas y su eficacia anticoagulante en modelos de mini-ECMO. Las ovejas mostraron mayor volumen de distribución (2,2 ± 0,4 L/kg) y semivida más corta (1,4 ± 0,1 h) que los humanos. Con 0,5 mg/kg, la supervivencia del dispositivo fue similar a la de la heparina en el modelo corto (rivaroxabán 51,3 ± 8,8 vs. heparina 57,5 ± 13,0 min) y en el prolongado (6,3 ± 1,6 vs. 6,3 ± 1,3 h).

Explore cómo esta investigación se conecta con la práctica clínica

Más estudios revisados por pares en la categoría «Desarrollo de fármacos».

• Novel Leech Antimicrobial Peptides — Hirunipins — Kumar et al. (2025)
• Medicinal Leech Draft Genome — Anticoagulant Gene Survey — Kvist S, Manzano-Marín A, de Carle D, Trontelj P, Siddall ME (2020)
• Effects of hirudotherapy on liver functions, lipid profile, and insulin sensitivity in rats with metabolic syndrome — Bilden A et al. (2026)
• Hirudotherapy in Medicine and Dentistry — Jha K et al. (2015)
• Medicinal leech therapy (hirudotherapy): a brief overview — Singh A (2010)
• Hirudoterapia en la presbiacusia precoz en liquidadores del accidente de Chernóbil durante los años posteriores a la catástrofe — Zabolotnyi D, Mishchanchuk N (2019)
• Investigation of oxidant-antioxidant status in patients treated with hirudotherapy: an experimental study — Sarikan I, Savas H (2024)
• Leech therapeutic applications — Abdualkader A et al. (2013)
• Non-Occlusive Mesenteric Ischemia Due to Hirudotherapy: A Case Report — Akalın Ç, Ekmen N (2020)
• Leech therapy: a history — Hyson J (2005)

Ver toda la investigación analizada por la ASH →