Microfluidic Modeling of Thrombolysis
Comparative study published in Arteriosclerosis, thrombosis, and vascular biology (2018)
Abstract
Objective- Despite the high clinical relevance of thrombolysis, models for its study in human flowing blood are lacking. Our objective was to develop a microfluidic model for comparative evaluation of thrombolytic therapeutic strategies. Approach and Results- Citrated human blood was supplemented with 3,3'-dihexyloxacarbocyanine iodide and Alexa Fluor 647 fibrinogen conjugate, recalcified, and perfused for 3 to 4 minutes at venous or arterial wall shear rate in microfluidic flow chambers coated with collagen and tissue factor to generate nonocclusive fluorescent thrombi. A second perfusion was performed for 10 minutes with rhodamine-6G-labeled citrated whole blood, supplemented or not with r-tPA (recombinant tissue-type plasminogen activator), fluorescein isothiocyanate-conjugated r-tPA, and Alexa Fluor 568 plasminogen conjugate. Plasminogen and r-tPA bound to preformed thrombi and r-tPA caused a concentration-dependent decrease in thrombus fibrin content (up to 50% reduction at 15 µg/mL r-tPA) as assessed by fluorescence microscopy. Fibrinolysis was confirmed by measurement of D-dimers in the output flow. Remarkably, despite ongoing fibrinolysis, new platelets continued to be recruited to the thrombus under lysis. Under the arterial condition, combining r-tPA with hirudin enhanced fibrinolysis but did not prevent the recruitment of new platelets, which was, however, prevented by antiplatelet agents (ticagrelor or the GPVI [glycoprotein VI]-blocking antigen-binding fragment 9O12). Conclusions- Our microfluidic thrombolysis model is suitable for studying thrombolysis and testing the efficacy of drugs used in combination with r-tPA. Real-time analysis of fibrin and platelets during r-tPA-mediated fibrinolysis at arterial or venous flow conditions showed that platelets continue to accumulate during fibrinolysis. Such platelet accumulation may impair r-tPA-mediated recanalization.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Objective- Despite the high clinical relevance of thrombolysis, models for its study in human flowing blood are lacking.
Por qué esto importa para la hirudoterapia
Este estudio desarrolló un modelo de trombólisis microfluídico en sangre humana en flujo, demostrando que el activador tisular del plasminógeno recombinante (r-tPA) produjo una reducción de fibrina dependiente de la concentración en trombos preformados, que las plaquetas continuaron reclutándose durante la lisis en curso, y que la combinación de r-tPA con hirudina potenció la fibrinólisis en condiciones arteriales sin impedir el reclutamiento plaquetario. El uso experimental directo de hirudina junto con r-tPA hace que este trabajo sea relevante para el interés de ASH en los anticoagulantes derivados de la sanguijuela y su integración en estrategias trombolíticas. Sin embargo, el trabajo es un modelo microfluídico in vitro que utiliza hirudina purificada como reactivo de investigación, no terapia con sanguijuelas ni el secretoma en sentido amplio, y no evalúa la eficacia clínica.
Citación
Microfluidic Modeling of Thrombolysis
Loyau S et al. · Arteriosclerosis, thrombosis, and vascular biology, 2018
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026