Inhibition of arterial thrombus formation in two canine models: comparison of ancrod, r-hirudin, and Ro 43-8857 GPIIb/IIIa antagonist
Animal model study published in Thrombosis and Haemostasis (1995)
Abstract
Inhibition of arterial thrombus formation by ancrod, a fibrinogen depleting agent isolated from a snake venom, r-hirudin, an inhibitor of thrombin-mediated fibrinogen cleavage, or the glycoprotein (GP)IIB/IIIa-receptor antagonist Ro 43-8857 interfering with fibrinogen binding to platelets, was evaluated in two canine models. As a marker of platelet-dependent thrombus formation, cyclic blood flow reductions (CFR) were induced in the left coronary artery (LAD) of mongrel dogs by mechanical injury of the endothelium combined with critical stenosis. In the second model CFRs were induced by thrombolysis of a copper coil-induced thrombus in the carotid artery. Blood flow rate during the reocclusion phase was used as an additional parameter of efficacy. The frequency of CFRs used a indicator of platelet aggregation and adhesion was significantly diminished by all treatments in both the carotid artery- and the LAD-model. In the LAD-model, following ancrod treatment, CFRs were correlated with plasma fibrinogen concentrations. Carotid artery blood flow after reperfusion, used as indicator of occlusive thrombus formation, rapidly declined to zero in the control group but remained at a high level after treatment with ancrod or r-hirudin. Ro 43-8857 at the selected dose improved flow rate only to a minor degree but prolonged the bleeding time from a mean value of 87.2 +/- 10.9 s (n = 24) to values > 300 s in 50% of the animals. Our results indicate that CFRs as indicator of platelet aggregation and adhesion are inhibited by either treatments. Blood flow as indicator of occlusive thrombus formation, however, is effectively improved by ancrod and r-hirudin only. Inhibition of fibrinogen binding to platelet GPIIb/IIIa receptors alone was found to be less potent antithrombotic principle in this model.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Two canine models of arterial thrombus formation: r-hirudin and ancrod (fibrinogen-depleter from snake venom) effectively maintained blood flow after carotid reperfusion, while Ro 43-8857 GPIIb/IIIa antagonist only modestly improved flow at the cost of greatly prolonged bleeding time.
Por qué esto importa para la hirudoterapia
Este estudio comparativo canino evaluó tres agentes antitrombóticos—ancrod, r-hirudina y el antagonista de GPIIb/IIIa Ro 43-8857—en dos modelos de trombosis arterial que involucraban reducciones cíclicas del flujo sanguíneo (CFRs) en las arterias coronaria LAD y carótida. Los tres agentes redujeron significativamente las CFRs en ambos modelos. Sin embargo, solo ancrod y r-hirudina mantuvieron eficazmente el flujo sanguíneo carotídeo posreperfusión; el antagonista de GPIIb-IIIa en la dosis seleccionada mostró solo una mejoría menor del flujo pero prolongó el tiempo de sangría (>300 s en el 50% de los animales). El resumen concluye que el flujo sanguíneo como indicador de formación de trombo oclusivo solo se mejora eficazmente con ancrod y r-hirudina. La relevancia para el dominio de ASH es indirecta: el estudio evalúa hirudina recombinante pero no menciona sanguijuelas ni hirudoterapia. El estudio está limitado por su modelo animal.
Citación
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026