Failure of thrombin inhibition to prevent intracoronary thrombosis in the dog (Folts model)
Animal model study published in Clinical Science (1996)
Abstract
1. Recurrent occlusion after thrombolysis may be caused by thrombin receptor-mediated platelet thrombosis occurring in a residual stenosis. To test the relative importance of the platelet thrombin receptor under conditions of high shear and endothelial damage (the Folts model of intracoronary thrombosis) we used the specific thrombin inhibitor recombinant hirudin. 2. A critical coronary artery stenosis overlying an area of crushed endothelium was used in a repeated measures study of eight open-chest anaesthetized dogs. In the control period, recurrent thrombosis occurred at an average rate (+/- SD) of 4.4 +/- 1.4 ml/min2. Infusion of recombinant hirudin at 1.6 mg h-1 kg-1 abolished recurrent thrombosis in three dogs, but the thrombosis rate averaged 4.7 +/- 2.9 ml/min2 in the remaining five animals. 3. Haematological measurements demonstrated the activity of recombinant hirudin: thrombin time rose from 13 +/- 3 s to > 165 s universally (P < 0.01), partial thromboplastin time rose from 14 +/- 2 s to 29 +/- 10 s (P < 0.01). Bleeding time rose from 2.3 +/- 0.8 min to 4.7 +/- 1.8 min (P < 0.05). 4. It is concluded that specific thrombin inhibition, despite affecting coagulation, is relatively ineffective in preventing intracoronary thrombosis under conditions of high shear.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Folts canine coronary stenosis model: recombinant hirudin 1.6 mg/h/kg abolished recurrent thrombosis in only 3 of 8 dogs despite robust pharmacological activity (thrombin time >165 s, prolonged aPTT, prolonged bleeding time) — supports the limits of thrombin-only blockade in platelet-rich high-shear thrombi.
Por qué esto importa para la hirudoterapia
Este estudio examinó la hirudina recombinante como inhibidor específico de la trombina en un modelo canino de trombosis intracoronaria (modelo de Folts, n=8, medidas repetidas) en condiciones de alto cizallamiento y daño endotelial. A pesar de la actividad anticoagulante sistémica confirmada (tiempo de trombina que aumentó de ~13 s a >165 s, aPTT de ~14 s a ~29 s, ambos P<0,01, y tiempo de sangría de ~2,3 a ~4,7 min, P<0,05), la hirudina abolió la trombosis recurrente solo en 3 de 8 perros; los cinco restantes presentaron tasas de trombosis comparables al control (4,7 ± 2,9 vs 4,4 ± 1,4 ml/min²). El resumen concluye que la inhibición específica de la trombina fue relativamente ineficaz para prevenir la trombosis intracoronaria en condiciones de alto cizallamiento. La relevancia para el ámbito de ASH es indirecta: el estudio evalúa hirudina recombinante pero no menciona sanguijuelas ni hirudoterapia. El estudio está limitado por su pequeña muestra canina y una dosis única de hirudina.
Citación
Failure of thrombin inhibition to prevent intracoronary thrombosis in the dog.
Belcher PR et al. · Clinical Science, 1996
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026