Comparison of enoxaparin, hirulog, and heparin as adjunctive antithrombotic therapy during thrombolysis with rtPA in the stenosed canine coronary artery
Animal model study published in Thrombosis and Haemostasis (1997)
Abstract
A canine model of electrolytic injury-induced coronary artery thrombosis and rtPA-induced thrombolysis was used to evaluate the relative antithrombotic efficacy of enoxaparin (a low molecular weight heparin), conventional therapy (heparin or heparin plus aspirin), and hirulog (a direct thrombin inhibitor), when used as adjunctive therapy during thrombolysis. After 60 min of clot aging, adjunctive therapy was begun at doses which elevated APTT approximately 2-fold over baseline. Fifteen minutes after the start of adjunctive therapy, recombinant tissue plasminogen activator (rtPA) was administered (100 microg/kg i.v. bolus + 20 microg/kg/min for 60 min). Adjunctive therapy continued for 1 h after termination of rtPA and blood flow was monitored for two additional hours. Enoxaparin (1 mg/kg i.v. bolus + 30 microg/kg/min, n = 10 for each treatment group) was the only adjunctive treatment that significantly increased the total minutes of flow (143 +/- 25 min out of a possible 240 min, vs 54 +/- 25 min for vehicle, p <0.05) and decreased thrombus mass (6.0 +/- 1.3 mg vs 11.8 +/- 3.2 mg for vehicle). Although hirulog (2 mg/kg i.v. bolus + 40 microg/kg/min) did not significantly increase the minutes of flow (120 +/- 27 min, p <0.06) or decrease thrombus mass (8.7 +/- 1.7 mg) compared to vehicle, these values were not significantly different than those measured in the enoxaparin group. However, the results with hirulog were achieved at the expense of a significantly greater increase in template bleeding time than that measured during enoxaparin treatment. Minutes of flow for heparin (50 U/kg i.v. bolus + 0.6 U/kg/min) and heparin plus aspirin (5 mg/kg i.v. bolus) were 69 +/- 20 and 60 +/- 23 min, respectively; thrombus masses were 8.2 +/- 1.3 and 7.3 +/- 1.0 mg, respectively. In summary, enoxaparin was more effective than conventional therapy in this model in terms of vessel patency and thrombus mass, and was as effective as hirulog, at least at a dose of hirulog that only modestly impaired hemostasis. Therefore, enoxaparin may prove to be a safe and effective alternative agent for adjunctive therapy during thrombolysis with rtPA.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Canine coronary thrombosis/thrombolysis model: enoxaparin yielded longer flow time (143 min) vs heparin (69 min); hirulog (hirudin-derived) at 2 mg/kg + 40 µg/kg/min was comparable to enoxaparin but with significantly greater bleeding time prolongation.
Por qué esto importa para la hirudoterapia
Este estudio comparativo utilizó un modelo canino de trombosis coronaria inducida por lesión electrolítica con trombólisis con rtPA para evaluar enoxaparina, hirulog (un inhibidor directo de la trombina), tratamiento convencional con heparina, y heparina más aspirina como tratamientos adyuvantes. La enoxaparina mejoró significativamente la permeabilidad vascular y redujo la masa del trombo en comparación con el vehículo, mientras que el hirulog mostró efectos intermedios que no alcanzaron significación estadística frente al vehículo pero fueron comparables a los de la enoxaparina. El tratamiento con hirulog se asoció con una prolongación del tiempo de sangrado significativamente mayor que la enoxaparina. El resumen no describe al hirulog como derivado de la hirudina ni relacionado con la sanguijuela; no existe una conexión defendible con la sanguijuela o la hirudoterapia a partir de este resumen. Se trata de un estudio en modelo animal sin datos en humanos.
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026