American Society of Hirudotherapy

Microfluidic Modeling of Thrombolysis

Comparative study published in Arteriosclerosis, thrombosis, and vascular biology (2018)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Observational studyDrug DevelopmentLoyau S et al. · 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.

Publication typeComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tVideo-Audio Media
Indexed MeSH termsAnticoagulantsBlood PlateletsFemaleFibrinFibrin Fibrinogen Degradation ProductsFibrinolysisFibrinolytic AgentsHumansLab-On-A-Chip DevicesMaleMicrofluidic Analytical TechniquesPlatelet Aggregation Inhibitors

Summary

Objective- Despite the high clinical relevance of thrombolysis, models for its study in human flowing blood are lacking.

Why This Matters for Hirudotherapy

This study developed a microfluidic thrombolysis model in flowing human blood, demonstrating that recombinant tissue plasminogen activator (r-tPA) produced concentration-dependent fibrin reduction in preformed thrombi, that platelets continued to recruit during ongoing lysis, and that combining r-tPA with hirudin enhanced fibrinolysis under arterial conditions without preventing platelet recruitment. The direct experimental use of hirudin alongside r-tPA makes this relevant to ASH's interest in leech-derived anticoagulants and their integration into thrombolytic strategies. However, the work is an in-vitro microfluidic model using purified hirudin as a research reagent, not leech therapy or the broader secretome, and does not test clinical efficacy.

Citation

Microfluidic Modeling of Thrombolysis

Loyau S et al. · Arteriosclerosis, thrombosis, and vascular biology, 2018

DOI

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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